Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study

Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study Matthew Hamby, Brian Egleston, Zachary Frosch, Ralphael Steiner, and 43 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7607922/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Mar, 2026 Read the published version in Blood Cancer Journal → Version 1 posted 9 You are reading this latest preprint version Abstract Plasmablastic lymphoma (PBL) is a rare, aggressive AIDS-related lymphoma observed in patients with immunosuppressed states as well as in immunocompetent individuals. We sought to determine survival outcomes, prognostic factors, and optimal treatment regimens in a large, contemporary cohort of patients with PBL in the United States. We performed a multicenter, retrospective cohort study, including 344 patients diagnosed with PBL between 2005 and 2022. Patients were stratified into cohorts according to underlying immune status. Survival outcomes were calculated using Kaplan-Meier statistics, with cohort-specific survival outcomes adjusted using propensity score-based weighting. Factors associated with outcomes were assessed via multivariable models using multiple imputation. The median age at diagnosis was 53 years, most patients were male (n = 270), and many had HIV (n = 164). The median OS was 5.0 years, with a median PFS of 1.4 years. Patients living with HIV had the best outcomes, whereas patients with prior organ transplantation had the worst outcomes. Use of higher intensity chemotherapy regimens and use of a proteasome inhibitor in the frontline setting did not show survival benefit. While there was no clear optimal treatment approach in the frontline setting, the median OS of 5.0 years is dramatically improved compared with historical controls. Health sciences/Diseases/Haematological diseases/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/B-cell lymphoma Biological sciences/Cancer/Haematological cancer/Lymphoma Figures Figure 1 Figure 2 Figure 3 Introduction Plasmablastic lymphoma (PBL) is a rare subtype of large B-cell lymphoma first described in 1997 in a small cohort of people living with HIV (PLWH). 1 In this initial cohort, it presented as a tumor in the oral cavity and was almost uniformly fatal. Since then, this entity has been identified post-transplant, in the setting of other immunosuppressed states, and even in otherwise immunocompetent patients. 2 PBL arises from the post-germinal center plasmablast, an activated B cell that ranges from immunoblastic to plasmacytic in morphology. 3 Immunophenotypically, PBL is characterized by expression of plasma cell markers (CD38, CD138) and most commonly a lack of B-cell markers (CD19, CD20, PAX5). 4 MYC rearrangement and EBV infection are believed to contribute to the pathogenesis of PBL, but their roles remain incompletely elucidated. 3 While first described as a lesion in the oral cavity/jaw, 1 PBL also presents in nodal and other extranodal sites. Many patients are diagnosed with advanced-stage disease that follows an aggressive clinical course. 5 While the prognosis of PBL was initially reported to be dismal, with a median overall survival of 8–15 months, recent studies have suggested improved outcomes. 6 , 7 The mainstay of initial management has been multiagent cytotoxic chemotherapy. Using CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and CHOP-like regimens, 1- and 2-year overall survival of 50–60% has been reported in small case series (n = 35). 8 The addition of biological agents commonly used for the management of plasma cell disorders, such as the proteasome inhibitor bortezomib or the CD38-directed monoclonal antibody daratumumab, may confer some benefit, but has not yet been tested in a randomized fashion. 9 , 10 Moreover, no well-defined standard of care exists. While NCCN guidelines consider CHOP to be inadequate and favor higher intensity regimens, 11 recent studies have called this into question. 6 , 12 , 13 Given its rarity, the literature on PBL is primarily limited to case reports and small case series, with larger multicenter and database studies appearing in recent years. 5 , 12 Still, significant unknowns remain surrounding the underlying biology and treatment of PBL. We aimed to perform a large, multicenter, retrospective study to understand disease characteristics, prognostic factors, and treatment-related outcomes in a contemporary cohort of PBL patients treated in the United States. Methods Study Design In this multicenter, retrospective cohort study, we identified 344 patients with PBL from 21 academic centers in the United States. Each center identified patients retrospectively using electronic medical records and submitted their anonymized data to the study center. Patients were included if they were ≥ 18 years old and diagnosed with PBL between 1/2005 and 12/2022. Patients were excluded if their diagnosis failed to meet the World Health Organization (WHO) diagnostic criteria 14 for PBL or their data were deemed incomplete. Patients included in the final analysis were grouped into one of four cohorts according to immune status (Fig. 1 ): patients with a previous history of HIV or HIV diagnosed concurrently with PBL were classified as HIV-PBL; patients with prior organ transplantation were classified as PBL arising as a post-transplant lymphoproliferative disorder (PTLD-PBL); those without HIV or prior transplant, but with known immunosuppression (e.g. underlying lymphoproliferative disorder, previous chemotherapy for malignancy, primary immunodeficiency, iatrogenic immunodeficiency, or autoimmune disease on current or prior immunosuppressive therapy with prednisone +/- biologic agents) were classified as PBL arising in the setting of other immunosuppressed states (OIS-PBL). All remaining patients who did not meet the criteria mentioned above were classified as immunocompetent PBL (IC-PBL). Objectives and Definitions The primary objective of this study was to determine the overall survival (OS) of the entire cohort. OS was defined as the time from PBL diagnosis to death from any cause or censoring at the time of last follow-up (FU). Secondary objectives included determining progression-free survival (PFS), non-relapse mortality (NRM), and treatment-related mortality (TRM), as well as assessing the prognostic impact of patient-, disease-, and treatment-related factors on survival outcomes. PFS was defined as the time from initiation of treatment to relapse/progression, death from any cause, or censoring at time of last FU. TRM was defined as death not due to PBL within 30 days of the most recent treatment. Patients were staged with CT or combined PET/CT. Bone marrow involvement was assessed either via bone marrow biopsy or PET/CT as per institutional practice. Involvement of the oral cavity/jaw, nasopharynx, oropharynx, paranasal sinuses, or orbit was defined as disease occurring in the head and neck. Immunophenotype was characterized by immunohistochemistry (IHC). EBV status was assessed either via IHC for latency membrane protein-1 (LMP1) or in situ hybridization (ISH) to EBV-encoded RNA (EBER). MYC rearrangement was assessed via fluorescence in situ hybridization (FISH), with rearrangement at any locus considered a positive result. As detailed in Supplemental Table 1 , we categorized chemotherapeutic backbone regimens received in the frontline (1L) setting into four groups: 1) standard-intensity CHOP/CHOP-like regimens, 2) dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH), 3) high intensity regimen with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (Hyper-CVAD) or cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC), and everything else as 4) "other". Second-line (2L) chemotherapeutic regimens are also detailed in Supplemental Table 1 . Statistical Analysis Continuous variables were summarized using medians with ranges and compared using the Wilcoxon rank-sum test. Categorical variables were summarized using frequencies and compared using the 𝛘 2 test. Unadjusted OS and PFS were calculated via the Kaplan-Meier method. Cox regressions were used to investigate variables associated with survival. Disease classification-specific survival figures were adjusted by inverse generalized propensity score-based weighting. 15 , 16 The PTLD-PBL group was excluded from the propensity score models due to the small sample size. Factors included in multivariable Cox regression and the multinomial logistic propensity score model included age, sex, year of diagnosis, race, ethnicity, immune status, ECOG performance status, Ann Arbor stage, extranodal disease, LDH elevation, IPI score, MYC rearrangement, EBV positivity by either LMP1 or EBER, 1L chemotherapeutic regimen, use of a proteasome inhibitor (PI) in the 1L, and use of CNS prophylaxis (PPx). The impact of consolidative autologous stem cell transplant (ASCT) was assessed in a separate sensitivity analysis. We used multiple imputation to account for missing data in the multivariable models. 17 Approval for this study was granted by the Institutional Review Board (IRB) of The University of Pennsylvania (Philadelphia, USA) and by the IRBs of all participating institutions. Results Patient characteristics Three hundred seventy-five patients were identified from 21 institutions. After excluding 31 patients who did not meet eligibility criteria, 344 patients were included in the final analysis: 48% had HIV-PBL (n = 164), 6% had PTLD-PBL (n = 19), 10% had OIS-PBL (n = 36), and 36% had IC-PBL (n = 125) (Fig. 1 ). The median age at diagnosis was 53 years (range 19–91) ( Table 1 ). Most patients were male (78%, n = 270); 67% of patients were White (n = 230), 17% were Black/African American (n = 59), and 33% were Hispanic/Latino (n = 114). The median age at diagnosis was significantly younger in the HIV-PBL cohort (46 years) compared with the PTLD-, OIS-, and IC-PBL cohorts (55, 67, and 68 years, respectively; p < 0.001). In the HIV-PBL cohort, the median CD4 count at time of PBL diagnosis was 147 cells/µL (range 1-986); 30% (n = 49) had a CD4 count < 100 cells/µL. Fifty-eight percent (n = 95) of patients were previously on antiretroviral therapy (ART) with a median CD4 count of 177 cells/µL. Thirty-six percent (n = 59) were ART-naïve and commenced ART at the time of PBL diagnosis, with a median CD4 count of 102 cells/µL. In the PTLD-PBL cohort, the median time from transplant to PBL diagnosis was 7.9 years (range 1–25). Of the 36 patients classified as having OIS-PBL, roughly half (n = 17) had an underlying lymphoproliferative disorder (LPD) (CLL, n = 6; FL, n = 3; DLBCL, n = 3; MZL, n = 2; WM, n = 1; HL, n = 1; MALT lymphoma, n = 1), with a median time from diagnosis of LPD to PBL of 12 years (range 6–26). Most patients were diagnosed with advanced-stage PBL [stage III (n = 22, 6%) or IV (n = 227, 66%)]. The majority had nodal disease (n = 215, 63%), and most had extranodal involvement (n = 316, 92%), with the most common extranodal site being the GI tract (n = 107, 31%). Bone marrow involvement was identified in 30% of patients who underwent a bone marrow biopsy (n = 63/212). Only 3% of patients presented with CNS involvement (n = 11). Twenty-seven percent presented with disease located in the head and neck (n = 94), with significantly more in the HIV-PBL cohort compared with the PTLD-, OIS-, and IC-PBL cohorts (32%, vs 11%, 8%, and 29%, respectively; p = 0.008). The most common immunophenotype was CD38+ (84%), CD138+ (87%), CD19- (83%), and CD20- (90%). Fifty-eight percent of tested samples had a detectable MYC rearrangement (n = 45/78), and this genomic abnormality was significantly more common in the HIV-PBL cohort at 74% (n = 26/35; p = 0.045). Likewise, 64% of tested samples were EBV + by EBER ISH, with the OIS- and IC-PBL cohorts significantly less likely to be EBER + compared with the HIV- and PTLD-PBL cohorts (p < 0.001). Survival Outcomes Median time until death or censoring for the entire cohort was 3.4y (range 0–17). Median OS was 5.0y (95% CI: 3.2–8.6), with 1y- and 2y- OS rates of 70% and 59%, respectively. Median PFS was 1.4y (95% CI: 1.0–3.0), with 1y- and 2y- PFS rates of 54% and 47%, respectively. The median OS after 1st relapse/progression was 0.6y (95% CI: 0.42–0.85). There were 170 deaths. The most common cause of death was PBL (n = 104), followed by infection (n = 25, with 12 being classified as TRM), and second primary malignancies (NSCLC, n = 2; HNSCC, n = 1; esophageal carcinoma, n = 1; mucinous adenocarcinoma, n = 1). The cause of death was unknown in 29 patients. When comparing survival outcomes by immune status (Fig. 2 a-b), the PTLD-PBL cohort had the poorest outcomes, with a median OS of 1.1y (95% CI: 0.43-not reached) and a median PFS of 1.0y (95% CI: 0.3–3.9). In contrast, the HIV-PBL cohort had the best outcomes, with a median OS of 7.2y (95% CI: 4.4–14.4) and a median PFS of 1.8y (95% CI: 0.8–4.5). Median OS was 2.3y (95% CI: 1.1-5.0) with a median PFS of 1.0y (95% CI: 0.5-4.0) in the OIS-PBL cohort. For the IC-PBL cohort, median OS was 4.1y (95% CI: 2.4-not reached) with a median PFS of 1.4y (95% CI: 0.8–4.1). Propensity Score Adjusted Survival We present unadjusted and propensity score-adjusted characteristics of the HIV-PBL, IC-PBL, and OIS-PBL cohorts in Supplemental Table 2 . Propensity score-adjusted OS medians for the non-PTLD-PBL cohorts were: 6.1 years (Interquartile Range [IQR]: 0.6-not reached) for HIV-PBL, 4.6 years (IQR: 1.0-13.8) for IC-PBL, and 4.4 years (IQR: 1.2-not reached) for OIS-PBL (Fig. 2 c). Propensity score-adjusted Cox regressions did not find significant OS differences among the three groups (HR = 1.0, 95% CI: 0.6–1.6 for IC-PBL; HR = 1.1, 95% CI: 0.6-2.0 for OIS-PBL, relative to the HIV-PBL cohort). Adjusted PFS medians were 1.4 years (IQR: 0.4–14.4) for HIV-PBL, 1.3 years (IQR: 0.5-not reached) for IC-PBL, and 3.1 years (IQR: 0.7-not reached) for OIS-PBL (Fig. 2 d). Propensity score-adjusted PFS models did not find significant differences among groups (HR = 0.9, 95% CI: 0.6–1.4 for IC-PBL; HR = 0.8, 95% CI: 0.4–1.5 for OIS-PBL, relative to HIV-PBL). Adjusted median NRM was not reached for any of the three cohorts (Fig. 3 ). Twenty-fifth percentile mortality was 14.4 years for HIV-PBL, and not reached for the IC-PBL or OIS-PBL cohorts. Subdistribution hazard ratios were 1.0 (95% CI: 0.6–1.5) for IC-PBL and 0.9 (95% CI: 0.5–1.6) for OIS-PBL, relative to HIV-PBL. Sensitivity Analysis Substantial differences between the cohorts impeded our ability to achieve an optimal balance of demographic and clinical factors among the three adjusted arms ( Supplemental Table 2 ). For example, the oldest patient was 72 in the HIV-PBL cohort versus 91 in the IC-PBL cohort. To ensure that residual confounding was not driving our findings, we estimated a logistic propensity score model using data only from patients in the HIV-PBL and IC-PBL cohorts who were 73 or younger. The OIS-PBL cohort was excluded from this analysis due to its small sample size. In this sensitivity analysis, we achieved better adjusted demographic balance across groups, and the results ( Supplemental Table 3 ) were similar to those of the three-group propensity score-adjusted model. Prognostic Factors The results of the survival analysis are detailed in Table 2 . In the multivariable Cox regression model utilizing multiple imputation methods, only advanced age, ECOG ≥2, advanced stage, and LDH elevation were associated with worse OS. We sought to more thoroughly assess the impact of several factors on survival outcomes, including CD4 count and MYC /EBV status. In the HIV-PBL cohort, a CD4 count ≥ 100 cells/µL at the time of PBL diagnosis was not associated with improved OS on multivariable analysis. Likewise, initiation of ART at the time of PBL diagnosis impacted neither OS nor PFS within the HIV-PBL cohort. Further, we assessed the impact of MYC translocation and EBV status on survival outcomes in the entire cohort: neither was an independent predictor of OS; however, EBV positivity was associated with improved PFS (HR = 0.57, 95% CI: 0.39–0.84, p = 0.004). The data on MYC rearrangement should be precautionary, as only 23% of patients were assessed for this abnormality. Frontline Treatment Of the 313 patients who received chemotherapy in the frontline setting, most received EPOCH-based regimens (70%; n = 220), 14% received CHOP/CHOP-like regimens (n = 44), and only 8% received Hyper-CVAD or CODOX-M/IVAC (n = 13, each). Many patients received agents in addition to chemotherapy in the 1L setting, with 34% receiving bortezomib (n = 105), 19% receiving rituximab (n = 60), and 4% receiving daratumumab (n = 12). Three patients received single-agent biologic treatment (bortezomib, n = 2; rituximab, n = 1). There was no apparent benefit to either OS or PFS with the use of EPOCH or other high-intensity chemotherapy regimens over standard intensity CHOP/CHOP-like regimens in both the univariable and multivariable models ( Table 2 ). This lack of OS and PFS benefit with use of EPOCH (compared with CHOP) was observed in a separate subgroup analysis of the HIV-PBL cohort as well. The overall and complete response rates (ORR, CRR) associated with EPOCH were 64% and 52%, respectively, versus 66% and 52% for CHOP. Of note, EPOCH was associated with higher rates of TRM than CHOP: 4% of EPOCH-treated patients died of TRM (n = 8) vs 2% of CHOP-treated patients (n = 1), p < 0.001. Furthermore, the use of a proteasome inhibitor failed to show either OS or PFS benefit on MVA (OS: HR = 0.99, 95% CI: 0.68–1.43, p = 0.950; PFS: HR = 1.10, 95% CI: 0.79–1.53, p = 0.591). Radiation, Autologous Stem Cell Transplant, and CNS Prophylaxis Eighteen percent of patients (n = 63) received RT as consolidation in the 1L setting, while 8% were consolidated with a hematopoietic ASCT at first remission (n = 27). Both RT and ASCT consolidation were independently associated with improved OS on UVA ( Table 2 ); however, only ASCT remained associated with improved OS (HR = 0.43, 95% CI: 0.19–0.97, p = 0.041) and PFS (HR = 0.49, 95% CI: 0.26–0.94, p = 0.032) when added to the multivariable Cox model in a separate sensitivity analysis. Thirty-three percent of patients (n = 113) received CNS prophylaxis in the form of intrathecal methotrexate/cytarabine (MTX/AraC; n = 83), high-dose MTX (n = 23), or both (n = 7). None of these treatment modalities were associated with improvements in OS or PFS in the multivariable Cox regression models. Only one of the patients who received CNS PPx (n = 113) experienced relapse involving the CNS, versus three of the patients who did not receive CNS PPx (n = 231). Second-Line Treatment Of the 138 patients who relapsed or progressed after receiving frontline treatment, 105 were treated with 2L therapies. The most commonly used 2L regimens included ICE (ifosfamide, carboplatin, and etoposide, n = 30), DHAP/similar (dexamethasone, high-dose cytarabine, and platinol, n = 23), low-intensity myeloma-like regimens (n = 19), and GemOx/similar (gemcitabine and oxaliplatin, n = 8) ( Supplemental Table 1 ). The ORRs for each of these regimens were: 50%, 39%, 26%, and 38%, respectively. Furthermore, 51% of these 105 patients were treated with biological agents alone or in addition to chemotherapy, such as daratumumab (n = 24), bortezomib (n = 27), rituximab (n = 9), or the immunomodulatory drug lenalidomide (n = 13). Several patients were consolidated in the second-line setting with either an autologous (n = 3) or allogeneic (n = 3) hematopoietic cell transplant (HCT). Of note, four patients received chimeric antigen receptor (CAR) T-cell therapy in the 2L setting (CD19-directed, n = 3; unknown target, n = 1), with only one alive at last FU (treated with lisocabtagene maraleucel). Discussion We performed a multicenter, retrospective study to better understand the underlying biology, survival outcomes, and optimal treatment of PBL in a contemporary cohort of patients in the US. To our knowledge, this is the largest real-world cohort of PBL patients to date. The main finding of this study was the markedly improved median OS in our cohort (5.0y) compared with a recently published international cohort (1.4y), albeit with similar median PFS (1.4y vs 8.4 mo). 12 This discrepancy may be explained by differences in second-line therapies available during the time frame of the two studies. Di Ciaccio et al. enrolled from 1999 to 2020, with only 35% of patients diagnosed after 2015, whereas we enrolled from 2005 to 2022, with 70% diagnosed after 2014. It is possible that increased use of modern biological agents in our more contemporaneous cohort explains the improvement in OS. The results of our study are broadly consistent with the current understanding of PBL. Known lymphoma risk factors that are usually captured in the IPI, such as advanced age, stage III/IV, ECOG ≥ 2, and LDH elevation, were associated with poor OS in our cohort. 18 Consistent with Di Ciaccio et al., we also found EBV negativity to be associated with poor PFS. 12 While there is mixed evidence regarding the prognostic impact of MYC rearrangement in PBL, 12,13,19,20 our results suggest that MYC +/EBV- PBL may represent an aggressive disease subtype; however, this requires further exploration, especially as data on MYC rearrangement was missing in many patients. EBV-positivity has been associated with different genetic features in Burkitt lymphoma (BL) when compared to EBV-negative cases. Recently, investigators identified that EBV + BL is characterized by fewer driver mutations, higher aberrant somatic hypermutation rates, and significantly more breakpoints upstream of MYC . 21 Therefore, interaction of EBV and MYC in PBL may result in different pathobiology underlying the observed differential outcomes. Furthermore, the association between female sex and poor OS on UVA (albeit with no association on MVA) is intriguing and warrants further investigation, particularly since males tend to have worse survival outcomes in most other lymphoma subtypes. 22 , 23 However, this observation may be related to the fact that male sex was predominant in the HIV-PBL cohort, which, in general, had better outcomes. Despite improvement in median OS, PBL remains a difficult-to-treat disease, as demonstrated by a 5-year OS rate of 50% in our cohort. Survival outcomes differed by immune status: HIV-PBL had the best outcomes (median OS 7.2y, median PFS 1.8y), while PTLD-PBL had the worst outcomes (median OS 1.1y, median PFS 1.0y). This may be due to a partially reversible immunodeficiency in PLWH, especially as about a third of the HIV-PBL cohort was previously ART-naïve. The poor survival outcomes of PTLD-PBL suggest this may represent an aggressive subtype, possibly related to the mostly irreversible, underlying, severe iatrogenic immunodeficiency in post-transplant patients. The underlying histopathologic features of this entity represent an area of future investigation. While there were various underlying immunosuppressed states in the OIS-PBL cohort, many were LPDs, raising the possibility that the PBL diagnosis represented a transformation event. Further investigation into the biology and clinical outcomes of this subgroup is warranted. The optimal treatment of PBL remains poorly defined due to the rarity of the disease and paucity of prospective clinical trials. While early studies of HIV-associated non-Hodgkin lymphomas suggested superior outcomes with EPOCH compared with CHOP and prompted NCCN guidelines to favor higher-intensity regimens, more recent retrospective studies have increasingly suggested no benefit to such an approach in PBL. 11 , 12 , 24 , 25 Our results similarly found no benefit with the use of EPOCH or other high-intensity regimens in the 1L setting over CHOP and therefore do not support the use of higher-intensity regimens, which are subject to higher rates of treatment-related morbidity and mortality. However, none of these are randomized prospective studies. Similarly, despite promising results in small, retrospective case series, 7 proteasome inhibitors failed to show frontline benefit in a recent multicenter study, 12 consistent with the findings in our cohort. Nevertheless, our study was not powered to definitively address the merit of biological agents classically used for plasma cell malignancies, such as bortezomib, daratumumab, and lenalidomide, in the management of PBL. However, the improved OS despite a similar PFS after 1L therapy in our US cohort could indicate a role for these agents in PBL. Prospective and ideally randomized clinical trials will be necessary to address this question. At present, a prospective randomized clinical trial in the US explores the combination of daratumumab with EPOCH, 26 while another study sponsored by the Fondazione Italiana Linfomi studies the combination of daratumumab, bortezomib, and dexamethasone for relapsed/refractory (r/r) PBL. 27 While there is no superior chemotherapeutic regimen in the 1L setting, RT and ASCT consolidation in our study were associated with improvements in OS, albeit with the inherent bias that to receive these treatments most patients would have needed first to achieve a complete response to initial therapy. However, as only 8% of the entire cohort underwent consolidative ASCT in first remission, the benefit of ASCT should be interpreted with caution and considered on a case-by-case basis in select, high-risk patients. In contrast, the use of CNS prophylaxis was not associated with OS and had no apparent effect on the risk of CNS recurrence, although the numbers were too small for firm conclusions. This is in line with recent observations in DLBCL that indicate a lack of benefit of CNS prophylaxis irrespective of modality. 28 , 29 Thus, the decision to use CNS prophylaxis in PBL should be highly individualized. Several small studies have investigated the management of r/r PBL with chemotherapeutic regimens such as ICE, with or without agents like daratumumab and lenalidomide. 30 , 31 , 32 , 33 We gathered data on 105 patients who underwent treatment in the r/r setting, and a comparison of survival outcomes using various 2L regimens, as well as the impact of use of biologic agents in the 2L setting will be addressed in future analyses. Further, while CAR T-cell therapy has revolutionized the treatment landscape of both DLBCL and multiple myeloma, its use in PBL has been limited. To our knowledge, there are only three published cases using CAR T-cell therapy in r/r PBL. One achieved a complete metabolic response, followed by disease progression at 5 months post-CD19-directed CAR T-cell infusion. 34 Two additional patients achieved complete remissions in response to BCMA-directed CAR T-cell products, with CR documented at 6 and 14 months post-infusion, respectively. 35 , 36 Herein, we report four patients treated with CAR T-cell therapy (CD19-directed, n = 3; unknown target, n = 1) with disappointing outcomes. It is unclear if the expression of CD19 and/or BCMA played a role in treatment choice. More data is needed regarding the safety, efficacy, and optimal target antigen of CAR T-cell therapies in the management of r/r PBL. There are several limitations to this study. Namely, given the retrospective nature of data collection, there was considerable variation in data availability between participating institutions. While some clinicopathologic variables were missing, we addressed missing data bias by using multiple imputation for multivariable analyses. Further, no centralized pathologic review was done to confirm a diagnosis of PBL in each patient; however, all participating institutions were major academic centers with experienced hematopathology departments. Despite the limitations of our study, it has several strengths, including our large sample size and granular, patient-level data. This allowed us to control for possible confounders by using propensity score adjustment and therefore significantly reduce bias. Further, this study expands the existing literature on this rare entity, augments findings of a recently published cohort from Australia, the UK, Canada, and Singapore, and at the same time contrasts them with our contemporary US cohort. 12 The prognosis of PBL has significantly improved over recent decades, particularly for HIV-PBL. While no optimal treatment has been established, more intense cytotoxic regimens may not confer a significant survival benefit. Although biological agents commonly used for plasma cell dyscrasias have been suggested to be of benefit based on small case series, their frontline use was not associated with improved outcomes in our study, and their role in PBL remains to be defined. This can only be done definitively in well-designed, prospective, and randomized clinical trials. Better understanding of the pathogenesis that underlies PBL based on oncogenic events and interactions with the host immune environment may also lead to more rationally targeted therapies and further improved outcomes. Declarations Competing interests The authors have no competing interests related to this work. Author Contributions MH and SKB conceived the study. MH collected, analyzed, and interpreted the data, and drafted, reviewed, and edited the manuscript. SKB coordinated enrollment from participating institutions, analyzed and interpreted the data, and reviewed and edited the manuscript. BLE led statistical design of the study, analyzed and interpreted the data, and reviewed and edited the manuscript. ZF and AN assisted in study design and reviewed and edited the manuscript. VC and EC assisted with IRB approval and coordination of data use agreements between the host site and participating institutions. RES, SST, GJL, JEA, RP, SA, JS, TV, RB, ARG, JJC, EH, CD, IAN, NMS, NNTD, JSS, AER, NK, AD, VS, PGR, AA, GS, AV, CM, AJO, GS, EA, SD, JMR, GM, TF, MP, DMA, WB, CG, VB, and MH collected data, reviewed, and edited the manuscript. Acknowledgements We acknowledge the contributions of all individuals at participating centers involved in study design and completion. Further, we acknowledge the patients from whom data was abstracted. This study was supported by AIDS Malignancy Consortium (AMC) Grant UM1CA121947 and Fox Chase Cancer Center NCI Grant P30CA006927. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Data Availability De-identified patient data is available upon request from the corresponding author and/or senior author, via email. References Delecluse HJ, Anagnostopoulos I, Dallenbach F, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood . 1997;89(4):1413–1420. Morscio J, Dierickx D, Nijs J, et al. Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases. Am J Surg Pathol . 2014;38(7): 875-886. Castillo JJ, Bibas M, Miranda RN. The biology and treatment of plasmablastic lymphoma. Blood . 2015;125(15):2323-2330. Vega F, Chang CC, Medeiros LJ, et al. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Modern Pathology . 2005;18(6):806-815. Hansen AR, Vardell VA, Fitzgerald LA. Epidemiologic Characteristics, Treatment Patterns, and Survival Analysis of Plasmablastic Lymphoma in the United States: A SEER and NCDB Analysis. Clinical Lymphoma Myeloma and Leukemia . 2024;24(4):e152-160. Tchernonog E, Faurie P, Coppo P, et al. Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group. Annals of Oncology . 2017;28(4):843-848. Castillo JJ, Guerrero‐Garcia T, Baldini F, et al. Bortezomib plus EPOCH is effective as frontline treatment in patients with plasmablastic lymphoma. British journal of haematology. 2019;184(4):679-682. Castillo JJ, Winer ES, Stachurski D, et al. Prognostic factors in chemotherapy-treated patients with HIV-associated plasmablastic lymphoma. The Oncologist . 2010;15(3):293-299. Noy A, Barta, SK, Kwon D, et al.Daratumumab with Dose-Adjusted EPOCH Is Feasible in Newly Diagnosed Plasmablastic Lymphoma: AIDS Malignancy Consortium 105. Blood. 2024;144(Supplement 1):870. Ryu, YK, Ricker, EC, Soderquist CR, et al. Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma. J. Clin. Med . 2022(11): 4928. NCCN guidelines version 3.2024. HIV-related B-cell lymphomas. Accessed October 17, 2024. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf Di Ciaccio PR, Polizzotto MN, Cwynarski K, et al. The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma. Blood . 2024;143(2):152-165. Castillo JJ, Furman M, Beltrán BE, et al. Human immunodeficiency virus‐associated plasmablastic lymphoma: poor prognosis in the era of highly active antiretroviral therapy. Cancer . 2012;118(21):5270-5277. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid tissues. IARC; 2017. McCaffrey DF, Ridgeway G, Morral AR. Propensity score estimation with boosted regression for evaluating causal effects in observational studies. Psychological Methods. 2004; 9(4):403–425. Ridgeway G, McCaffrey D, Morral A, et al. Toolkit for Weighting and Analysis of Nonequivalent Groups: A Tutorial for the Twang Package. Raghunathan TE, Lepkowski JM, Van Hoewyk J, et al. A Multivariate Technique for Multiply Imputing Missing Values Using a Sequence of Regression Models. Survey methodology . 2001;27(1):85-95. International Non-Hodgkin's Lymphoma Prognostic Factors Project, "A Predictive Model for Aggressive Non-Hodgkin's Lymphoma." New England Journal of Medicine, vol. 329, no. 14, 1993, pp. 987-994. Jessa R, Chien N, Villa D, et al. Clinicopathological characteristics and long-term outcomes of plasmablastic lymphoma in British Columbia. Br J Haematol. 2022;199: 230-238. Witte HM, Hertel N, Merz H, et al. Clinicopathological characteristics and MYC status determine treatment outcome in plasmablastic lymphoma: a multicenter study of 76 consecutive patients. Blood Cancer J. 2020;10: 63. Thomas N, Dreval K, Gerhard DS, et al. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma. Blood. 2023;141(8): 904–916. Radkiewicz C, Bruchfeld JB, Weibull CE, et al. Sex differences in lymphoma incidence and mortality by subtype: A population-based study. Am J Hematol. 2023;98(1):23-30. Pfreundschuh M. Age and sex in non-Hodgkin lymphoma therapy: it's not all created equal, or is it?. American Society of Clinical Oncology Educational Book. 2017;37:505-11. Barta SK, Xue X, Wang D, et al. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients. Blood. 2013;122(19):3251-62. Tchernonog E, Faurie P, Coppo P, et al. Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group. Annals of Oncology. 2017;28(4):843-848. A Multicenter, Open-Label Feasibility Study of Daratumumab With Dose-Adjusted EPOCH in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV. Study to Evaluate Combined Treatment of Daratumumab, Bortezomib and Dexamethasone in PBL Patients Klanova M, Sehn LH, Bence-Bruckler I, et al. Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL. Blood . 2019;133(9):919-926. Victor Manuel Orellana-Noia VM, Reed DR, McCook AA, et al. Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions. Blood. 2022;139(3):413–423. Dittus C, Miller JA, Wehbie R, Castillo JJ. Daratumumab with ifosfamide, carboplatin and etoposide for the treatment of relapsed plasmablastic lymphoma. Br J Haematol. 2022;198: e32-e34. Cheng L, Song Q, Liu M, et al. Case report: successful management of a refractory plasmablastic lymphoma patient with tislelizumab and lenalidomide. Front Immunol. 2021; 12:702593. Marrero WD, Cruz-Chacon A, Castillo C, Cabanillas F. Successful use of bortezomib-lenalidomide combination as treatment for a patient with plasmablastic lymphoma. Clin Lymphoma Myeloma Leuk. 2018; 18: e275-e277. Ando K, Imaizumi Y, Kobayashi Y, et al. Bortezomib- and Lenalidomide-Based Treatment of Refractory Plasmablastic Lymphoma. Oncol Res Treat. 2020;43(3):112-116. Raychaudhuri R, Qualtieri J, and Garfall AL. Axicabtagene ciloleucel for CD19+ plasmablastic lymphoma. Am J Hematol. 2020;95:E28-E30. Raghunandan S, Pauly M, Blum WG, et al. BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma. J Immunother Cancer. 2023;11(5):e006684. Feng S, Xiong Y, Liu W, et al. BCMA CAR-T induces complete and durable remission in plasmablastic lymphoma synchronous transformation of chronic lymphocytic leukemia: Case report and literature review. Crit Rev Oncol Hematol. 2025;205:104551. Tables Table 1. Patient Characteristics, Clinical Presentation, and Treatment Patterns by Immune Status Cohort Total n = 344 (%) HIV-PBL n = 164 (%) PTLD-PBL n = 19 (%) OIS-PBL n = 36 (%) IC-PBL n = 125 (%) p-value* Age at diagnosis (y) Median (Range) < 60 ≥ 60 53 (19-91) 212 (62) 132 (38) 46 (19-76) 150 (91) 14 (9) 55 (23-75) 11 (58) 8 (42) 67 (21-88) 10 (28) 26 (72) 68 (20-91) 41 (33) 84 (67) <0.001 Sex Male Female 270 (78) 74 (22) 141 (86) 23 (14) 13 (68) 6 (32) 22 (61) 14 (39) 94 (75) 31 (25) 0.003 Year of diagnosis 2005-2009 2010-2014 2015-2019 2020-2022 29 (8) 75 (22) 158 (46) 82 (24) 23 (14) 40 (24) 75 (46) 26 (16) 0 (0) 6 (32) 7 (36) 6 (32) 2 (6) 5 (14) 15 (42) 14 (38) 4 (3) 24 (19) 61 (49) 36 (29) 0.003 Race White Black / African American Other Unknown 230 (67) 59 (17) 34 (10) 21 (6) 90 (55) 44 (27) 23 (14) 7 (4) 16 (85) 1 (5) 1 (5) 1 (5) 28 (77) 5 (14) 1 (3) 2 (6) 96 (77) 9 (7) 9 (7) 11 (9) <0.001 Ethnicity Hispanic/Latino Non-Hispanic/Latino Other/Unknown 114 (33) 206 (60) 24 (7) 62 (38) 94 (57) 8 (5) 2 (11) 16 (84) 1 (5) 13 (36) 19 (53) 4 (11) 37 (30) 77 (62) 11 (8) 0.143 ECOG Performance Status ≤ 1 2+ Unknown 227 (66) 74 (22) 43 (12) 104 (64) 35 (21) 25 (15) 13 (68) 2 (11) 4 (21) 25 (69) 9 (25) 2 (6) 85 (68) 28 (22) 12 (10) 0.773 Ann Arbor Stage I II III IV Unknown 52 (15) 33 (10) 22 (6) 227 (66) 10 (3) 15 (9) 18 (11) 13 (8) 114 (70) 4 (2) 4 (21) 0 (0) 0 (0) 13 (68) 2 (11) 6 (16) 2 (6) 4 (11) 24 (67) 0 (0) 27 (22) 13 (10) 5 (4) 76 (61) 4 (3) 0.071 Nodal Disease Yes No Unknown 215 (63) 112 (33) 17 (4) 112 (68) 44 (27) 8 (5) 8 (42) 11 (58) 0 (0) 23 (64) 13 (36) 0 (0) 72 (58) 44 (35) 9 (7) 0.046 Extranodal Disease Yes No Unknown 316 (92) 24 (7) 4 (1) 149 (91) 12 (7) 3 (2) 17 (89) 2 (11) 0 (0) 33 (92) 3 (8) 0 (0) 117 (94) 7 (5) 1 (1) 0.837 LDH Elevation >1x ULN Not Elevated Unknown 177 (51) 124 (36) 43 (13) 100 (61) 48 (29) 16 (10) 7 (37) 7 (37) 5 (26) 21 (58) 13 (36) 2 (6) 49 (39) 56 (45) 20 (16) 0.009 IPI at diagnosis, mean (SD) 2.51 (1.32) 2.50 (1.14) 2.38 (1.39) 2.88 (1.34) 2.42 (1.52) 0.423 MYC Rearrangement + - Unknown 45 (13) 33 (10) 266 (77) 26 (16) 9 (5) 129 (79) 2 (11) 2 (11) 15 (78) 7 (19) 6 (17) 23 (64) 10 (8) 16 (13) 99 (79) 0.045 CNS Involvement Yes No Unknown 11 (3) 329 (96) 4 (1) 6 (4) 155 (95) 3 (1) 0 (0) 19 (100) 0 (0) 0 (0) 36 (100) 0 (0) 5 (4) 119 (95) 1 (1) 0.529 Head/Neck Involvement Yes No Unknown 94 (27) 246 (72) 4 (1) 53 (32) 108 (66) 3 (2) 2 (11) 17 (89) 0 (0) 3 (8) 33 (92) 0 (0) 36 (29) 88 (70) 1 (1) 0.008 EBV+ by LMP or EBER + - Unknown 194 (56) 112 (33) 38 (11) 25 (15) 118 (72) 21 (13) 5 (26) 13 (68) 1 (5) 23 (64) 13 (36) 0 (0) 59 (47) 50 (40) 16 (13) <0.001 Chemo Regimen in 1L** CHOP/CHOP-like EPOCH Hyper-CVAD or CODOX-M/IVAC Other 44 (14) 220 (64) 26 (8) 19 (6) 17 (10) 110 (67) 17 (10) 9 (5) 1 (5) 15 (79) 1 (5) 1 (5) 10 (28) 19 (53) 0 (0) 2 (6) 16 (13) 76 (61) 8 (6) 7 (6) 0.073 Additional Agents Used in 1L Proteasome Inhibitor Rituximab Daratumumab 105 (31) 60 (17) 12 (4) 47 (29) 31 (19) 7 (4) 5 (26) 4 (21) 2 (11) 8 (22) 11 (31) 2 (6) 45 (36) 14 (11) 1 (1) 0.028 CNS PPx in 1L IT MTX and/or AraC HD MTX None Unknown 90 (26) 23 (7) 179 (52) 52 (15) 50 (30) 16 (10) 74 (45) 24 (15) 2 (11) 0 (0) 11 (58) 6 (31) 5 (14) 0 (0) 25 (69) 6 (17) 33 (26) 7 (6) 69 (55) 16 (13) 0.024 Consolidative RT in 1L Yes No Unknown 63 (18) 270 (78) 11 (3) 21 (13) 142 (86) 1 (1) 3 (16) 14 (74) 2 (10) 6 (17) 30 (83) 0 (0) 33 (26) 84 (68) 8 (6) 0.014 Consolidative ASCT in 1L Yes No Unknown 27 (8) 307 (89) 10 (3) 13 (8) 150 (91) 1 (1) 0 (0) 17 (89) 2 (11) 4 (11) 32 (89) 0 (0) 10 (8) 108 (86) 7 (6) 0.580 *Bolded p-values are statistically significant. P-values do not account for missing data rows. SD = Standard deviation. **More detailed description in Supplemental Table 1. Table 2. Survival Analysis using multiply imputed data Risk Factor Univariable Analysis, OS Cox Regression (Multiple Imputation), OS HR 95% CI p-value* HR 95% CI p-value* Cohort (vs HIV-PBL) PTLD-PBL IC-PBL OIS-PBL 1.51 1.17 1.59 0.82-2.78 0.83-1.64 0.99-2.54 0.187 0.370 0.055 1.91 0.80 0.93 0.92-3.99 0.47-1.37 0.49-1.79 0.083 0.418 0.832 Age (years) 1.02 1.01-1.03 <0.001 1.02 1.00-1.03 0.018 Female sex 1.52 1.08-2.15 0.018 1.26 0.84-1.88 0.263 Year of diagnosis (vs 2005-2009) 2010-2014 2015-2019 2020-2022 1.49 1.88 1.61 0.79-2.81 1.02-3.46 0.83-3.12 0.220 0.042 0.162 1.10 1.65 1.51 0.50-2.4 0.79-3.41 0.67-3.38 0.817 0.180 0.322 Race (vs White) Black/African American Other 1.58 0.49 1.09-2.30 0.24-1.00 0.016 0.049 1.43 0.63 0.91-2.23 0.28-1.40 0.118 0.253 Ethnicity (vs Hispanic/Latino) Non-Hispanic/Latino 1.35 0.96-1.89 0.087 1.08 0.72-1.62 0.717 ECOG 2+ (vs <2) 2.59 1.82-3.68 <0.001 1.91 1.14-3.2 0.014 Stage III/IV (vs I/II) 2.52 1.64-3.86 <0.001 1.75 1.02-3.02 0.043 Extranodal disease 1.57 1.16-2.13 0.004 1.27 0.84-1.93 0.258 LDH elevation 3.04 2.12-4.36 <0.001 2.63 1.65-4.20 <0.001 IPI (per one point increase) 1.45 1.25-1.67 <0.001 1.05 0.84-1.32 0.643 MYC rearrangement 1.34 0.27-6.68 0.712 1.26 0.26-6.06 0.761 EBV+ by either LMP1 or EBER 0.59 0.42-0.84 0.004 0.71 0.46-1.10 0.126 1L Regimen (vs CHOP) EPOCH High-Intensity Other 0.77 1.01 1.33 0.49-1.21 0.52-1.97 0.64-2.76 0.254 0.983 0.448 0.65 1.36 0.89 0.39-1.07 0.62-3.01 0.43-1.83 0.091 0.444 0.742 PI in 1L 1.05 0.76-1.46 0.766 0.99 0.68-1.43 0.950 CNS PPx (vs none) IT MTX/AraC HD IV MTX 0.76 0.87 0.52-1.10 0.50-1.52 0.149 0.621 0.81 0.69 0.51-1.28 0.34-1.39 0.363 0.295 Consolidative RT in 1L 0.60 0.38-0.93 0.024 0.93 0.57-1.52 0.768 *Bolded p-values are statistically significant Additional Declarations Yes there is potential conflict of interest. Frosch: Genmab: Research Funding; AbbVie: Research Funding; Acerta: Research Funding; BeiGene: Research Funding; Merck: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; Fox Chase Cancer Center: Current Employment; Roche: Research Funding; AstraZeneca: Research Funding; Antegene: Research Funding; Sanofi: Research Funding. Steiner:GSK: Research Funding; Rafael Pharmaceuticals: Research Funding; BMS: Research Funding; Seagen: Research Funding. Noy:clearview: Consultancy; epizyme: Consultancy; OncLIve: Honoraria; PER: Honoraria; NSCI: Honoraria; janssen Global: Consultancy, Other: drug provided for research; EUSA: Consultancy; health advance: Consultancy; Cornerstone Pharma: Honoraria, Research Funding; Medallion Healthcare: Honoraria; AstraZeneca: Consultancy; guidepoint global: Consultancy; ADC therapeutics: Consultancy; Beigene: Consultancy. Amengual:Incyte: Consultancy; Ipsen: Consultancy; ADCT: Consultancy; Astrazeneca: Consultancy. Ahmed:Merck: Research Funding; Janssen: Research Funding; Nektar: Research Funding; Genmab: Research Funding; Caribou: Research Funding; Bristol Myers Squibb: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; ADC Therapeutics: Consultancy. Voorhees: Ad Boards: Genmab/AbbVie, ADC Therapeutics. Consultancy: Recordati, Genmab. Research: Kite, Incyte/Morphosys, Genmab/AbbVie, Recordati. Baiocchi:Codiak Biosciences: Research Funding; ATARABio: Consultancy, Other: Advisory Board; Viracta Therapeutics: Consultancy, Current holder of stock options in a privately-held company, Other: Advisory Board; Prelude Therapeutics: Other: Advisory Board, Research Funding; Agenus: Other: Involved in supply of drug (vaccine) and product development. Castillo:AbbVie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Mustang Bio: Consultancy; Kite Pharmaceuticals: Consultancy; LOXO: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Cellectar Biosciences: Consultancy, Research Funding. Mehta-Shah: Research Funding: Bristol Myers Squibb, Celgene, Verastem/Secura Bio Pharmaceuticals, Innate Pharmaceuticals, Roche/Genentech, Corvus Pharmaceuticals, AstraZeneca, Daiichi Sankyo; Morphosys, SeaGen, Shanghai Yingli, Dizal. Consultant: AstraZeneca, Autolous, C4 Therapeutics, Kiowa Hakka Kirin, Karyopharma, Ono Pharmaceuticals, Pfizer, Secura Bio, Daiichi Sankyo, Genentech, Janssen . Riedell: Consultant and/or advisory board member for AbbVie, Novartis, BMS, ADC Therapeutics, Kite/Gilead, Genentech/Roche, Pfizer, Miltenyi, CVS Caremark, Genmab, BeiGene, and Janssen/Pharmacyclics. He has received travel support from Adaptive Biotechnologies. Institutional research support from AbbVie, BMS, Kite Pharma, Novartis, Xencor, Fate Therapeutics, Genentech, and Cellectis. Milrod: AstraZeneca, Hematology R&D, Waltham, Massachusetts. Olszewski:Genmab, Schrodinger, Genentech, Inc., Precision Biosciences, Artiva, Pfizer, Kymera Therapeutics: Research Funding; Genmab, Schrodinger, ADC Therapeutics, BeiGene, Bristol-Myers Squibb: Consultancy. Feldman:Astrazeneca: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; DAIICHI: Research Funding; Kymera: Research Funding; Merck: Research Funding; ADCT: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Genmab: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Corvus: Research Funding; TESSA: Research Funding; Trillium: Research Funding; Portola: Research Funding; Alexion: Research Funding; Genomic Testing Cooperative: Current equity holder in private company; OMI: Current equity holder in private company. Galvez: Honoraria from Kite from advisory board, Honoraria from AstraZeneca from advisory board. Hamadani: Research Support/Funding: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: Genmab, CRISPR, Allovir, Caribou, Autolus, Forte Biosciences, Byondis, Kite, Daiichi Sankyo Speaker’s Bureau: AstraZeneca, ADC Therapeutics, BeiGene, Kite, Sobi. Barta:Acrotech: Consultancy; Kyowa Kirin: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Daiichi Sankyo: Consultancy. 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patient.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7607922/v1/5ff243f75ea57523dfa7c8ba.png"},{"id":92505545,"identity":"1a041c90-5de2-4edf-99df-0be01d249846","added_by":"auto","created_at":"2025-09-30 12:30:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84820,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eSurvival Outcomes by Immune Status Cohort\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eKaplan-Meier curves comparing: unadjusted overall survival by immune status (2a); unadjusted progression-free survival by immune status (2b); propensity score-adjusted overall survival by immune status (2c); propensity score-adjusted progression-free survival by immune status (2d). Median survival (years) with 95% CI is denoted next to each curve, with p-values representing significant difference in median survival between cohorts.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7607922/v1/f72d6e7509d0d2afe82147ef.png"},{"id":92504692,"identity":"2a25a1db-be97-4981-bd14-88328f739f4d","added_by":"auto","created_at":"2025-09-30 12:22:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":49876,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003ePropensity Score Adjusted Non-Relapse Mortality (NRM) by Immune Status Cohort\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eCumulative incidence of death due to causes other than PBL, by immune status cohort.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7607922/v1/9c094c334c4db1d799899004.png"},{"id":105618100,"identity":"0ef43755-ad78-413d-9235-3bbfd60c8dd7","added_by":"auto","created_at":"2026-03-28 07:10:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1764801,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7607922/v1/68540a9d-f777-48ac-b03c-d87150a768f3.pdf"},{"id":92506307,"identity":"8f176fc9-fcf6-4294-9dee-9f376584b976","added_by":"auto","created_at":"2025-09-30 12:38:59","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":279879,"visible":true,"origin":"","legend":"\u003cp\u003eSupplemental Tables, Figures\u003c/p\u003e","description":"","filename":"SupplementalTablesandFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7607922/v1/9d3ad8d93668197b5623ffda.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential conflict of interest.\nFrosch: Genmab: Research Funding; AbbVie: Research Funding; Acerta: Research Funding; BeiGene: Research Funding; Merck: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; Fox Chase Cancer Center: Current Employment; Roche: Research Funding; AstraZeneca: Research Funding; Antegene: Research Funding; Sanofi: Research Funding. Steiner:GSK: Research Funding; Rafael Pharmaceuticals: Research Funding; BMS: Research Funding; Seagen: Research Funding. Noy:clearview: Consultancy; epizyme: Consultancy; OncLIve: Honoraria; PER: Honoraria; NSCI: Honoraria; janssen Global: Consultancy, Other: drug provided for research; EUSA: Consultancy; health advance: Consultancy; Cornerstone Pharma: Honoraria, Research Funding; Medallion Healthcare: Honoraria; AstraZeneca: Consultancy; guidepoint global: Consultancy; ADC therapeutics: Consultancy; Beigene: Consultancy. Amengual:Incyte: Consultancy; Ipsen: Consultancy; ADCT: Consultancy; Astrazeneca: Consultancy. Ahmed:Merck: Research Funding; Janssen: Research Funding; Nektar: Research Funding; Genmab: Research Funding; Caribou: Research Funding; Bristol Myers Squibb: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; ADC Therapeutics: Consultancy. Voorhees: Ad Boards: Genmab/AbbVie, ADC Therapeutics. Consultancy: Recordati, Genmab. Research: Kite, Incyte/Morphosys, Genmab/AbbVie, Recordati. Baiocchi:Codiak Biosciences: Research Funding; ATARABio: Consultancy, Other: Advisory Board; Viracta Therapeutics: Consultancy, Current holder of stock options in a privately-held company, Other: Advisory Board; Prelude Therapeutics: Other: Advisory Board, Research Funding; Agenus: Other: Involved in supply of drug (vaccine) and product development. Castillo:AbbVie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Mustang Bio: Consultancy; Kite Pharmaceuticals: Consultancy; LOXO: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Cellectar Biosciences: Consultancy, Research Funding. Mehta-Shah: Research Funding: Bristol Myers Squibb, Celgene, Verastem/Secura Bio Pharmaceuticals, Innate Pharmaceuticals, Roche/Genentech, Corvus Pharmaceuticals, AstraZeneca, Daiichi Sankyo; Morphosys, SeaGen, Shanghai Yingli, Dizal. Consultant: AstraZeneca, Autolous, C4 Therapeutics, Kiowa Hakka Kirin, Karyopharma, Ono Pharmaceuticals, Pfizer, Secura Bio, Daiichi Sankyo, Genentech, Janssen . Riedell: Consultant and/or advisory board member for AbbVie, Novartis, BMS, ADC Therapeutics, Kite/Gilead, Genentech/Roche, Pfizer, Miltenyi, CVS Caremark, Genmab, BeiGene, and Janssen/Pharmacyclics. He has received travel support from Adaptive Biotechnologies. Institutional research support from AbbVie, BMS, Kite Pharma, Novartis, Xencor, Fate Therapeutics, Genentech, and Cellectis. Milrod: AstraZeneca, Hematology R\u0026D, Waltham, Massachusetts. Olszewski:Genmab, Schrodinger, Genentech, Inc., Precision Biosciences, Artiva, Pfizer, Kymera Therapeutics: Research Funding; Genmab, Schrodinger, ADC Therapeutics, BeiGene, Bristol-Myers Squibb: Consultancy. Feldman:Astrazeneca: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; DAIICHI: Research Funding; Kymera: Research Funding; Merck: Research Funding; ADCT: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Genmab: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Corvus: Research Funding; TESSA: Research Funding; Trillium: Research Funding; Portola: Research Funding; Alexion: Research Funding; Genomic Testing Cooperative: Current equity holder in private company; OMI: Current equity holder in private company. Galvez: Honoraria from Kite from advisory board, Honoraria from AstraZeneca from advisory board. Hamadani: Research Support/Funding: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: Genmab, CRISPR, Allovir, Caribou, Autolus, Forte Biosciences, Byondis, Kite, Daiichi Sankyo Speaker’s Bureau: AstraZeneca, ADC Therapeutics, BeiGene, Kite, Sobi. Barta:Acrotech: Consultancy; Kyowa Kirin: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Daiichi Sankyo: Consultancy.","formattedTitle":"Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePlasmablastic lymphoma (PBL) is a rare subtype of large B-cell lymphoma first described in 1997 in a small cohort of people living with HIV (PLWH).\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e In this initial cohort, it presented as a tumor in the oral cavity and was almost uniformly fatal. Since then, this entity has been identified post-transplant, in the setting of other immunosuppressed states, and even in otherwise immunocompetent patients.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePBL arises from the post-germinal center plasmablast, an activated B cell that ranges from immunoblastic to plasmacytic in morphology.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Immunophenotypically, PBL is characterized by expression of plasma cell markers (CD38, CD138) and most commonly a lack of B-cell markers (CD19, CD20, PAX5).\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e \u003cem\u003eMYC\u003c/em\u003e rearrangement and EBV infection are believed to contribute to the pathogenesis of PBL, but their roles remain incompletely elucidated.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhile first described as a lesion in the oral cavity/jaw,\u003csup\u003e1\u003c/sup\u003e PBL also presents in nodal and other extranodal sites. Many patients are diagnosed with advanced-stage disease that follows an aggressive clinical course.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e While the prognosis of PBL was initially reported to be dismal, with a median overall survival of 8\u0026ndash;15 months, recent studies have suggested improved outcomes.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The mainstay of initial management has been multiagent cytotoxic chemotherapy. Using CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and CHOP-like regimens, 1- and 2-year overall survival of 50\u0026ndash;60% has been reported in small case series (n\u0026thinsp;=\u0026thinsp;35).\u003csup\u003e8\u003c/sup\u003e The addition of biological agents commonly used for the management of plasma cell disorders, such as the proteasome inhibitor bortezomib or the CD38-directed monoclonal antibody daratumumab, may confer some benefit, but has not yet been tested in a randomized fashion.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Moreover, no well-defined standard of care exists. While NCCN guidelines consider CHOP to be inadequate and favor higher intensity regimens,\u003csup\u003e11\u003c/sup\u003e recent studies have called this into question.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eGiven its rarity, the literature on PBL is primarily limited to case reports and small case series, with larger multicenter and database studies appearing in recent years.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Still, significant unknowns remain surrounding the underlying biology and treatment of PBL. We aimed to perform a large, multicenter, retrospective study to understand disease characteristics, prognostic factors, and treatment-related outcomes in a contemporary cohort of PBL patients treated in the United States.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design\u003c/h2\u003e\u003cp\u003eIn this multicenter, retrospective cohort study, we identified 344 patients with PBL from 21 academic centers in the United States. Each center identified patients retrospectively using electronic medical records and submitted their anonymized data to the study center. Patients were included if they were \u0026ge;\u0026thinsp;18 years old and diagnosed with PBL between 1/2005 and 12/2022. Patients were excluded if their diagnosis failed to meet the World Health Organization (WHO) diagnostic criteria\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e for PBL or their data were deemed incomplete. Patients included in the final analysis were grouped into one of four cohorts according to immune status (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e): patients with a previous history of HIV or HIV diagnosed concurrently with PBL were classified as HIV-PBL; patients with prior organ transplantation were classified as PBL arising as a post-transplant lymphoproliferative disorder (PTLD-PBL); those without HIV or prior transplant, but with known immunosuppression (e.g. underlying lymphoproliferative disorder, previous chemotherapy for malignancy, primary immunodeficiency, iatrogenic immunodeficiency, or autoimmune disease on current or prior immunosuppressive therapy with prednisone +/- biologic agents) were classified as PBL arising in the setting of other immunosuppressed states (OIS-PBL). All remaining patients who did not meet the criteria mentioned above were classified as immunocompetent PBL (IC-PBL).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eObjectives and Definitions\u003c/h3\u003e\n\u003cp\u003eThe primary objective of this study was to determine the overall survival (OS) of the entire cohort. OS was defined as the time from PBL diagnosis to death from any cause or censoring at the time of last follow-up (FU). Secondary objectives included determining progression-free survival (PFS), non-relapse mortality (NRM), and treatment-related mortality (TRM), as well as assessing the prognostic impact of patient-, disease-, and treatment-related factors on survival outcomes. PFS was defined as the time from initiation of treatment to relapse/progression, death from any cause, or censoring at time of last FU. TRM was defined as death not due to PBL within 30 days of the most recent treatment.\u003c/p\u003e\u003cp\u003ePatients were staged with CT or combined PET/CT. Bone marrow involvement was assessed either via bone marrow biopsy or PET/CT as per institutional practice. Involvement of the oral cavity/jaw, nasopharynx, oropharynx, paranasal sinuses, or orbit was defined as disease occurring in the head and neck. Immunophenotype was characterized by immunohistochemistry (IHC). EBV status was assessed either via IHC for latency membrane protein-1 (LMP1) or in situ hybridization (ISH) to EBV-encoded RNA (EBER). \u003cem\u003eMYC\u003c/em\u003e rearrangement was assessed via fluorescence in situ hybridization (FISH), with rearrangement at any locus considered a positive result.\u003c/p\u003e\u003cp\u003eAs detailed in \u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e, we categorized chemotherapeutic backbone regimens received in the frontline (1L) setting into four groups: 1) standard-intensity CHOP/CHOP-like regimens, 2) dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH), 3) high intensity regimen with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (Hyper-CVAD) or cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC), and everything else as 4) \"other\". Second-line (2L) chemotherapeutic regimens are also detailed in \u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eContinuous variables were summarized using medians with ranges and compared using the Wilcoxon rank-sum test. Categorical variables were summarized using frequencies and compared using the \u0026#120536;\u003csup\u003e2\u003c/sup\u003e test.\u003c/p\u003e\u003cp\u003eUnadjusted OS and PFS were calculated via the Kaplan-Meier method. Cox regressions were used to investigate variables associated with survival. Disease classification-specific survival figures were adjusted by inverse generalized propensity score-based weighting.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e The PTLD-PBL group was excluded from the propensity score models due to the small sample size. Factors included in multivariable Cox regression and the multinomial logistic propensity score model included age, sex, year of diagnosis, race, ethnicity, immune status, ECOG performance status, Ann Arbor stage, extranodal disease, LDH elevation, IPI score, \u003cem\u003eMYC\u003c/em\u003e rearrangement, EBV positivity by either LMP1 or EBER, 1L chemotherapeutic regimen, use of a proteasome inhibitor (PI) in the 1L, and use of CNS prophylaxis (PPx). The impact of consolidative autologous stem cell transplant (ASCT) was assessed in a separate sensitivity analysis. We used multiple imputation to account for missing data in the multivariable models.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e Approval for this study was granted by the Institutional Review Board (IRB) of The University of Pennsylvania (Philadelphia, USA) and by the IRBs of all participating institutions.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics\u003c/h2\u003e\u003cp\u003eThree hundred seventy-five patients were identified from 21 institutions. After excluding 31 patients who did not meet eligibility criteria, 344 patients were included in the final analysis: 48% had HIV-PBL (n\u0026thinsp;=\u0026thinsp;164), 6% had PTLD-PBL (n\u0026thinsp;=\u0026thinsp;19), 10% had OIS-PBL (n\u0026thinsp;=\u0026thinsp;36), and 36% had IC-PBL (n\u0026thinsp;=\u0026thinsp;125) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age at diagnosis was 53 years (range 19\u0026ndash;91) (\u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e). Most patients were male (78%, n\u0026thinsp;=\u0026thinsp;270); 67% of patients were White (n\u0026thinsp;=\u0026thinsp;230), 17% were Black/African American (n\u0026thinsp;=\u0026thinsp;59), and 33% were Hispanic/Latino (n\u0026thinsp;=\u0026thinsp;114). The median age at diagnosis was significantly younger in the HIV-PBL cohort (46 years) compared with the PTLD-, OIS-, and IC-PBL cohorts (55, 67, and 68 years, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eIn the HIV-PBL cohort, the median CD4 count at time of PBL diagnosis was 147 cells/\u0026micro;L (range 1-986); 30% (n\u0026thinsp;=\u0026thinsp;49) had a CD4 count\u0026thinsp;\u0026lt;\u0026thinsp;100 cells/\u0026micro;L. Fifty-eight percent (n\u0026thinsp;=\u0026thinsp;95) of patients were previously on antiretroviral therapy (ART) with a median CD4 count of 177 cells/\u0026micro;L. Thirty-six percent (n\u0026thinsp;=\u0026thinsp;59) were ART-na\u0026iuml;ve and commenced ART at the time of PBL diagnosis, with a median CD4 count of 102 cells/\u0026micro;L.\u003c/p\u003e\u003cp\u003eIn the PTLD-PBL cohort, the median time from transplant to PBL diagnosis was 7.9 years (range 1\u0026ndash;25). Of the 36 patients classified as having OIS-PBL, roughly half (n\u0026thinsp;=\u0026thinsp;17) had an underlying lymphoproliferative disorder (LPD) (CLL, n\u0026thinsp;=\u0026thinsp;6; FL, n\u0026thinsp;=\u0026thinsp;3; DLBCL, n\u0026thinsp;=\u0026thinsp;3; MZL, n\u0026thinsp;=\u0026thinsp;2; WM, n\u0026thinsp;=\u0026thinsp;1; HL, n\u0026thinsp;=\u0026thinsp;1; MALT lymphoma, n\u0026thinsp;=\u0026thinsp;1), with a median time from diagnosis of LPD to PBL of 12 years (range 6\u0026ndash;26).\u003c/p\u003e\u003cp\u003eMost patients were diagnosed with advanced-stage PBL [stage III (n\u0026thinsp;=\u0026thinsp;22, 6%) or IV (n\u0026thinsp;=\u0026thinsp;227, 66%)]. The majority had nodal disease (n\u0026thinsp;=\u0026thinsp;215, 63%), and most had extranodal involvement (n\u0026thinsp;=\u0026thinsp;316, 92%), with the most common extranodal site being the GI tract (n\u0026thinsp;=\u0026thinsp;107, 31%). Bone marrow involvement was identified in 30% of patients who underwent a bone marrow biopsy (n\u0026thinsp;=\u0026thinsp;63/212). Only 3% of patients presented with CNS involvement (n\u0026thinsp;=\u0026thinsp;11). Twenty-seven percent presented with disease located in the head and neck (n\u0026thinsp;=\u0026thinsp;94), with significantly more in the HIV-PBL cohort compared with the PTLD-, OIS-, and IC-PBL cohorts (32%, vs 11%, 8%, and 29%, respectively; p\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e\u003cp\u003eThe most common immunophenotype was CD38+ (84%), CD138+ (87%), CD19- (83%), and CD20- (90%). Fifty-eight percent of tested samples had a detectable \u003cem\u003eMYC\u003c/em\u003e rearrangement (n\u0026thinsp;=\u0026thinsp;45/78), and this genomic abnormality was significantly more common in the HIV-PBL cohort at 74% (n\u0026thinsp;=\u0026thinsp;26/35; p\u0026thinsp;=\u0026thinsp;0.045). Likewise, 64% of tested samples were EBV\u0026thinsp;+\u0026thinsp;by EBER ISH, with the OIS- and IC-PBL cohorts significantly less likely to be EBER\u0026thinsp;+\u0026thinsp;compared with the HIV- and PTLD-PBL cohorts (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eSurvival Outcomes\u003c/h2\u003e\u003cp\u003eMedian time until death or censoring for the entire cohort was 3.4y (range 0\u0026ndash;17). Median OS was 5.0y (95% CI: 3.2\u0026ndash;8.6), with 1y- and 2y- OS rates of 70% and 59%, respectively. Median PFS was 1.4y (95% CI: 1.0\u0026ndash;3.0), with 1y- and 2y- PFS rates of 54% and 47%, respectively. The median OS after 1st relapse/progression was 0.6y (95% CI: 0.42\u0026ndash;0.85). There were 170 deaths. The most common cause of death was PBL (n\u0026thinsp;=\u0026thinsp;104), followed by infection (n\u0026thinsp;=\u0026thinsp;25, with 12 being classified as TRM), and second primary malignancies (NSCLC, n\u0026thinsp;=\u0026thinsp;2; HNSCC, n\u0026thinsp;=\u0026thinsp;1; esophageal carcinoma, n\u0026thinsp;=\u0026thinsp;1; mucinous adenocarcinoma, n\u0026thinsp;=\u0026thinsp;1). The cause of death was unknown in 29 patients.\u003c/p\u003e\u003cp\u003eWhen comparing survival outcomes by immune status (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea-b), the PTLD-PBL cohort had the poorest outcomes, with a median OS of 1.1y (95% CI: 0.43-not reached) and a median PFS of 1.0y (95% CI: 0.3\u0026ndash;3.9). In contrast, the HIV-PBL cohort had the best outcomes, with a median OS of 7.2y (95% CI: 4.4\u0026ndash;14.4) and a median PFS of 1.8y (95% CI: 0.8\u0026ndash;4.5). Median OS was 2.3y (95% CI: 1.1-5.0) with a median PFS of 1.0y (95% CI: 0.5-4.0) in the OIS-PBL cohort. For the IC-PBL cohort, median OS was 4.1y (95% CI: 2.4-not reached) with a median PFS of 1.4y (95% CI: 0.8\u0026ndash;4.1).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePropensity Score Adjusted Survival\u003c/h3\u003e\n\u003cp\u003eWe present unadjusted and propensity score-adjusted characteristics of the HIV-PBL, IC-PBL, and OIS-PBL cohorts in \u003cb\u003eSupplemental Table\u0026nbsp;2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003ePropensity score-adjusted OS medians for the non-PTLD-PBL cohorts were: 6.1 years (Interquartile Range [IQR]: 0.6-not reached) for HIV-PBL, 4.6 years (IQR: 1.0-13.8) for IC-PBL, and 4.4 years (IQR: 1.2-not reached) for OIS-PBL (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). Propensity score-adjusted Cox regressions did not find significant OS differences among the three groups (HR\u0026thinsp;=\u0026thinsp;1.0, 95% CI: 0.6\u0026ndash;1.6 for IC-PBL; HR\u0026thinsp;=\u0026thinsp;1.1, 95% CI: 0.6-2.0 for OIS-PBL, relative to the HIV-PBL cohort). Adjusted PFS medians were 1.4 years (IQR: 0.4\u0026ndash;14.4) for HIV-PBL, 1.3 years (IQR: 0.5-not reached) for IC-PBL, and 3.1 years (IQR: 0.7-not reached) for OIS-PBL (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). Propensity score-adjusted PFS models did not find significant differences among groups (HR\u0026thinsp;=\u0026thinsp;0.9, 95% CI: 0.6\u0026ndash;1.4 for IC-PBL; HR\u0026thinsp;=\u0026thinsp;0.8, 95% CI: 0.4\u0026ndash;1.5 for OIS-PBL, relative to HIV-PBL).\u003c/p\u003e\u003cp\u003eAdjusted median NRM was not reached for any of the three cohorts (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Twenty-fifth percentile mortality was 14.4 years for HIV-PBL, and not reached for the IC-PBL or OIS-PBL cohorts. Subdistribution hazard ratios were 1.0 (95% CI: 0.6\u0026ndash;1.5) for IC-PBL and 0.9 (95% CI: 0.5\u0026ndash;1.6) for OIS-PBL, relative to HIV-PBL.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eSensitivity Analysis\u003c/h3\u003e\n\u003cp\u003eSubstantial differences between the cohorts impeded our ability to achieve an optimal balance of demographic and clinical factors among the three adjusted arms (\u003cb\u003eSupplemental Table\u0026nbsp;2\u003c/b\u003e). For example, the oldest patient was 72 in the HIV-PBL cohort versus 91 in the IC-PBL cohort. To ensure that residual confounding was not driving our findings, we estimated a logistic propensity score model using data only from patients in the HIV-PBL and IC-PBL cohorts who were 73 or younger. The OIS-PBL cohort was excluded from this analysis due to its small sample size. In this sensitivity analysis, we achieved better adjusted demographic balance across groups, and the results (\u003cb\u003eSupplemental Table\u0026nbsp;3\u003c/b\u003e) were similar to those of the three-group propensity score-adjusted model.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePrognostic Factors\u003c/h2\u003e\u003cp\u003eThe results of the survival analysis are detailed in \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e. In the multivariable Cox regression model utilizing multiple imputation methods, only advanced age, ECOG \u0026ge;2, advanced stage, and LDH elevation were associated with worse OS. We sought to more thoroughly assess the impact of several factors on survival outcomes, including CD4 count and \u003cem\u003eMYC\u003c/em\u003e/EBV status. In the HIV-PBL cohort, a CD4 count \u0026ge; 100 cells/\u0026micro;L at the time of PBL diagnosis was not associated with improved OS on multivariable analysis. Likewise, initiation of ART at the time of PBL diagnosis impacted neither OS nor PFS within the HIV-PBL cohort. Further, we assessed the impact of \u003cem\u003eMYC\u003c/em\u003e translocation and EBV status on survival outcomes in the entire cohort: neither was an independent predictor of OS; however, EBV positivity was associated with improved PFS (HR\u0026thinsp;=\u0026thinsp;0.57, 95% CI: 0.39\u0026ndash;0.84, p\u0026thinsp;=\u0026thinsp;0.004). The data on \u003cem\u003eMYC\u003c/em\u003e rearrangement should be precautionary, as only 23% of patients were assessed for this abnormality.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eFrontline Treatment\u003c/h2\u003e\u003cp\u003eOf the 313 patients who received chemotherapy in the frontline setting, most received EPOCH-based regimens (70%; n\u0026thinsp;=\u0026thinsp;220), 14% received CHOP/CHOP-like regimens (n\u0026thinsp;=\u0026thinsp;44), and only 8% received Hyper-CVAD or CODOX-M/IVAC (n\u0026thinsp;=\u0026thinsp;13, each). Many patients received agents in addition to chemotherapy in the 1L setting, with 34% receiving bortezomib (n\u0026thinsp;=\u0026thinsp;105), 19% receiving rituximab (n\u0026thinsp;=\u0026thinsp;60), and 4% receiving daratumumab (n\u0026thinsp;=\u0026thinsp;12). Three patients received single-agent biologic treatment (bortezomib, n\u0026thinsp;=\u0026thinsp;2; rituximab, n\u0026thinsp;=\u0026thinsp;1). There was no apparent benefit to either OS or PFS with the use of EPOCH or other high-intensity chemotherapy regimens over standard intensity CHOP/CHOP-like regimens in both the univariable and multivariable models (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e). This lack of OS and PFS benefit with use of EPOCH (compared with CHOP) was observed in a separate subgroup analysis of the HIV-PBL cohort as well. The overall and complete response rates (ORR, CRR) associated with EPOCH were 64% and 52%, respectively, versus 66% and 52% for CHOP. Of note, EPOCH was associated with higher rates of TRM than CHOP: 4% of EPOCH-treated patients died of TRM (n\u0026thinsp;=\u0026thinsp;8) vs 2% of CHOP-treated patients (n\u0026thinsp;=\u0026thinsp;1), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Furthermore, the use of a proteasome inhibitor failed to show either OS or PFS benefit on MVA (OS: HR\u0026thinsp;=\u0026thinsp;0.99, 95% CI: 0.68\u0026ndash;1.43, p\u0026thinsp;=\u0026thinsp;0.950; PFS: HR\u0026thinsp;=\u0026thinsp;1.10, 95% CI: 0.79\u0026ndash;1.53, p\u0026thinsp;=\u0026thinsp;0.591).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eRadiation, Autologous Stem Cell Transplant, and CNS Prophylaxis\u003c/h2\u003e\u003cp\u003eEighteen percent of patients (n\u0026thinsp;=\u0026thinsp;63) received RT as consolidation in the 1L setting, while 8% were consolidated with a hematopoietic ASCT at first remission (n\u0026thinsp;=\u0026thinsp;27). Both RT and ASCT consolidation were independently associated with improved OS on UVA (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e); however, only ASCT remained associated with improved OS (HR\u0026thinsp;=\u0026thinsp;0.43, 95% CI: 0.19\u0026ndash;0.97, p\u0026thinsp;=\u0026thinsp;0.041) and PFS (HR\u0026thinsp;=\u0026thinsp;0.49, 95% CI: 0.26\u0026ndash;0.94, p\u0026thinsp;=\u0026thinsp;0.032) when added to the multivariable Cox model in a separate sensitivity analysis.\u003c/p\u003e\u003cp\u003eThirty-three percent of patients (n\u0026thinsp;=\u0026thinsp;113) received CNS prophylaxis in the form of intrathecal methotrexate/cytarabine (MTX/AraC; n\u0026thinsp;=\u0026thinsp;83), high-dose MTX (n\u0026thinsp;=\u0026thinsp;23), or both (n\u0026thinsp;=\u0026thinsp;7). None of these treatment modalities were associated with improvements in OS or PFS in the multivariable Cox regression models. Only one of the patients who received CNS PPx (n\u0026thinsp;=\u0026thinsp;113) experienced relapse involving the CNS, versus three of the patients who did not receive CNS PPx (n\u0026thinsp;=\u0026thinsp;231).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eSecond-Line Treatment\u003c/h2\u003e\u003cp\u003eOf the 138 patients who relapsed or progressed after receiving frontline treatment, 105 were treated with 2L therapies. The most commonly used 2L regimens included ICE (ifosfamide, carboplatin, and etoposide, n\u0026thinsp;=\u0026thinsp;30), DHAP/similar (dexamethasone, high-dose cytarabine, and platinol, n\u0026thinsp;=\u0026thinsp;23), low-intensity myeloma-like regimens (n\u0026thinsp;=\u0026thinsp;19), and GemOx/similar (gemcitabine and oxaliplatin, n\u0026thinsp;=\u0026thinsp;8) (\u003cb\u003eSupplemental Table\u0026nbsp;1\u003c/b\u003e). The ORRs for each of these regimens were: 50%, 39%, 26%, and 38%, respectively.\u003c/p\u003e\u003cp\u003eFurthermore, 51% of these 105 patients were treated with biological agents alone or in addition to chemotherapy, such as daratumumab (n\u0026thinsp;=\u0026thinsp;24), bortezomib (n\u0026thinsp;=\u0026thinsp;27), rituximab (n\u0026thinsp;=\u0026thinsp;9), or the immunomodulatory drug lenalidomide (n\u0026thinsp;=\u0026thinsp;13). Several patients were consolidated in the second-line setting with either an autologous (n\u0026thinsp;=\u0026thinsp;3) or allogeneic (n\u0026thinsp;=\u0026thinsp;3) hematopoietic cell transplant (HCT). Of note, four patients received chimeric antigen receptor (CAR) T-cell therapy in the 2L setting (CD19-directed, n\u0026thinsp;=\u0026thinsp;3; unknown target, n\u0026thinsp;=\u0026thinsp;1), with only one alive at last FU (treated with lisocabtagene maraleucel).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe performed a multicenter, retrospective study to better understand the underlying biology, survival outcomes, and optimal treatment of PBL in a contemporary cohort of patients in the US. To our knowledge, this is the largest real-world cohort of PBL patients to date.\u003c/p\u003e\u003cp\u003eThe main finding of this study was the markedly improved median OS in our cohort (5.0y) compared with a recently published international cohort (1.4y), albeit with similar median PFS (1.4y vs 8.4 mo).\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e This discrepancy may be explained by differences in second-line therapies available during the time frame of the two studies. Di Ciaccio et al. enrolled from 1999 to 2020, with only 35% of patients diagnosed after 2015, whereas we enrolled from 2005 to 2022, with 70% diagnosed after 2014. It is possible that increased use of modern biological agents in our more contemporaneous cohort explains the improvement in OS.\u003c/p\u003e\u003cp\u003eThe results of our study are broadly consistent with the current understanding of PBL. Known lymphoma risk factors that are usually captured in the IPI, such as advanced age, stage III/IV, ECOG\u0026thinsp;\u0026ge;\u0026thinsp;2, and LDH elevation, were associated with poor OS in our cohort.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Consistent with Di Ciaccio et al., we also found EBV negativity to be associated with poor PFS.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhile there is mixed evidence regarding the prognostic impact of \u003cem\u003eMYC\u003c/em\u003e rearrangement in PBL,\u003csup\u003e12,13,19,20\u003c/sup\u003e our results suggest that \u003cem\u003eMYC\u003c/em\u003e+/EBV- PBL may represent an aggressive disease subtype; however, this requires further exploration, especially as data on \u003cem\u003eMYC\u003c/em\u003e rearrangement was missing in many patients. EBV-positivity has been associated with different genetic features in Burkitt lymphoma (BL) when compared to EBV-negative cases. Recently, investigators identified that EBV\u0026thinsp;+\u0026thinsp;BL is characterized by fewer driver mutations, higher aberrant somatic hypermutation rates, and significantly more breakpoints upstream of \u003cem\u003eMYC\u003c/em\u003e.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Therefore, interaction of EBV and \u003cem\u003eMYC\u003c/em\u003e in PBL may result in different pathobiology underlying the observed differential outcomes. Furthermore, the association between female sex and poor OS on UVA (albeit with no association on MVA) is intriguing and warrants further investigation, particularly since males tend to have worse survival outcomes in most other lymphoma subtypes.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e However, this observation may be related to the fact that male sex was predominant in the HIV-PBL cohort, which, in general, had better outcomes.\u003c/p\u003e\u003cp\u003eDespite improvement in median OS, PBL remains a difficult-to-treat disease, as demonstrated by a 5-year OS rate of 50% in our cohort. Survival outcomes differed by immune status: HIV-PBL had the best outcomes (median OS 7.2y, median PFS 1.8y), while PTLD-PBL had the worst outcomes (median OS 1.1y, median PFS 1.0y). This may be due to a partially reversible immunodeficiency in PLWH, especially as about a third of the HIV-PBL cohort was previously ART-na\u0026iuml;ve. The poor survival outcomes of PTLD-PBL suggest this may represent an aggressive subtype, possibly related to the mostly irreversible, underlying, severe iatrogenic immunodeficiency in post-transplant patients. The underlying histopathologic features of this entity represent an area of future investigation. While there were various underlying immunosuppressed states in the OIS-PBL cohort, many were LPDs, raising the possibility that the PBL diagnosis represented a transformation event. Further investigation into the biology and clinical outcomes of this subgroup is warranted.\u003c/p\u003e\u003cp\u003eThe optimal treatment of PBL remains poorly defined due to the rarity of the disease and paucity of prospective clinical trials. While early studies of HIV-associated non-Hodgkin lymphomas suggested superior outcomes with EPOCH compared with CHOP and prompted NCCN guidelines to favor higher-intensity regimens, more recent retrospective studies have increasingly suggested no benefit to such an approach in PBL.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Our results similarly found no benefit with the use of EPOCH or other high-intensity regimens in the 1L setting over CHOP and therefore do not support the use of higher-intensity regimens, which are subject to higher rates of treatment-related morbidity and mortality. However, none of these are randomized prospective studies.\u003c/p\u003e\u003cp\u003eSimilarly, despite promising results in small, retrospective case series,\u003csup\u003e7\u003c/sup\u003e proteasome inhibitors failed to show frontline benefit in a recent multicenter study,\u003csup\u003e12\u003c/sup\u003e consistent with the findings in our cohort. Nevertheless, our study was not powered to definitively address the merit of biological agents classically used for plasma cell malignancies, such as bortezomib, daratumumab, and lenalidomide, in the management of PBL. However, the improved OS despite a similar PFS after 1L therapy in our US cohort could indicate a role for these agents in PBL. Prospective and ideally randomized clinical trials will be necessary to address this question. At present, a prospective randomized clinical trial in the US explores the combination of daratumumab with EPOCH,\u003csup\u003e26\u003c/sup\u003e while another study sponsored by the Fondazione Italiana Linfomi studies the combination of daratumumab, bortezomib, and dexamethasone for relapsed/refractory (r/r) PBL.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhile there is no superior chemotherapeutic regimen in the 1L setting, RT and ASCT consolidation in our study were associated with improvements in OS, albeit with the inherent bias that to receive these treatments most patients would have needed first to achieve a complete response to initial therapy. However, as only 8% of the entire cohort underwent consolidative ASCT in first remission, the benefit of ASCT should be interpreted with caution and considered on a case-by-case basis in select, high-risk patients.\u003c/p\u003e\u003cp\u003eIn contrast, the use of CNS prophylaxis was not associated with OS and had no apparent effect on the risk of CNS recurrence, although the numbers were too small for firm conclusions. This is in line with recent observations in DLBCL that indicate a lack of benefit of CNS prophylaxis irrespective of modality.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Thus, the decision to use CNS prophylaxis in PBL should be highly individualized.\u003c/p\u003e\u003cp\u003eSeveral small studies have investigated the management of r/r PBL with chemotherapeutic regimens such as ICE, with or without agents like daratumumab and lenalidomide.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e We gathered data on 105 patients who underwent treatment in the r/r setting, and a comparison of survival outcomes using various 2L regimens, as well as the impact of use of biologic agents in the 2L setting will be addressed in future analyses. Further, while CAR T-cell therapy has revolutionized the treatment landscape of both DLBCL and multiple myeloma, its use in PBL has been limited. To our knowledge, there are only three published cases using CAR T-cell therapy in r/r PBL. One achieved a complete metabolic response, followed by disease progression at 5 months post-CD19-directed CAR T-cell infusion.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e Two additional patients achieved complete remissions in response to BCMA-directed CAR T-cell products, with CR documented at 6 and 14 months post-infusion, respectively.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e Herein, we report four patients treated with CAR T-cell therapy (CD19-directed, n\u0026thinsp;=\u0026thinsp;3; unknown target, n\u0026thinsp;=\u0026thinsp;1) with disappointing outcomes. It is unclear if the expression of CD19 and/or BCMA played a role in treatment choice. More data is needed regarding the safety, efficacy, and optimal target antigen of CAR T-cell therapies in the management of r/r PBL.\u003c/p\u003e\u003cp\u003eThere are several limitations to this study. Namely, given the retrospective nature of data collection, there was considerable variation in data availability between participating institutions. While some clinicopathologic variables were missing, we addressed missing data bias by using multiple imputation for multivariable analyses. Further, no centralized pathologic review was done to confirm a diagnosis of PBL in each patient; however, all participating institutions were major academic centers with experienced hematopathology departments.\u003c/p\u003e\u003cp\u003eDespite the limitations of our study, it has several strengths, including our large sample size and granular, patient-level data. This allowed us to control for possible confounders by using propensity score adjustment and therefore significantly reduce bias. Further, this study expands the existing literature on this rare entity, augments findings of a recently published cohort from Australia, the UK, Canada, and Singapore, and at the same time contrasts them with our contemporary US cohort.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe prognosis of PBL has significantly improved over recent decades, particularly for HIV-PBL. While no optimal treatment has been established, more intense cytotoxic regimens may not confer a significant survival benefit. Although biological agents commonly used for plasma cell dyscrasias have been suggested to be of benefit based on small case series, their frontline use was not associated with improved outcomes in our study, and their role in PBL remains to be defined. This can only be done definitively in well-designed, prospective, and randomized clinical trials. Better understanding of the pathogenesis that underlies PBL based on oncogenic events and interactions with the host immune environment may also lead to more rationally targeted therapies and further improved outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors have no competing interests related to this work.\u003c/p\u003e\n\u003ch2\u003eAuthor Contributions\u003c/h2\u003e\n\u003cp\u003eMH and SKB conceived the study. MH collected, analyzed, and interpreted the data, and drafted, reviewed, and edited the manuscript. SKB coordinated enrollment from participating institutions, analyzed and interpreted the data, and reviewed and edited the manuscript. BLE led statistical design of the study, analyzed and interpreted the data, and reviewed and edited the manuscript. ZF and AN assisted in study design and reviewed and edited the manuscript. VC and EC assisted with IRB approval and coordination of data use agreements between the host site and participating institutions. RES, SST, GJL, JEA, RP, SA, JS, TV, RB, ARG, JJC, EH, CD, IAN, NMS, NNTD, JSS, AER, NK, AD, VS, PGR, AA, GS, AV, CM, AJO, GS, EA, SD, JMR, GM, TF, MP, DMA, WB, CG, VB, and MH collected data, reviewed, and edited the manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eWe acknowledge the contributions of all individuals at participating centers involved in study design and completion. Further, we acknowledge the patients from whom data was abstracted. This study was supported by AIDS Malignancy Consortium (AMC) Grant UM1CA121947 and Fox Chase Cancer Center NCI Grant P30CA006927. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eDe-identified patient data is available upon request from the corresponding author and/or senior author, via email.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDelecluse HJ, Anagnostopoulos I, Dallenbach F, et al. Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. \u003cem\u003eBlood\u003c/em\u003e. 1997;89(4):1413\u0026ndash;1420.\u003c/li\u003e\n\u003cli\u003eMorscio J, Dierickx D, Nijs J, et al. Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases. \u003cem\u003eAm J Surg Pathol\u003c/em\u003e. 2014;38(7): 875-886.\u003c/li\u003e\n\u003cli\u003eCastillo JJ, Bibas M, Miranda RN. The biology and treatment of plasmablastic lymphoma. \u003cem\u003eBlood\u003c/em\u003e. 2015;125(15):2323-2330.\u003c/li\u003e\n\u003cli\u003eVega F, Chang CC, Medeiros LJ, et al. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. \u003cem\u003eModern Pathology\u003c/em\u003e. 2005;18(6):806-815.\u003c/li\u003e\n\u003cli\u003eHansen AR, Vardell VA, Fitzgerald LA. Epidemiologic Characteristics, Treatment Patterns, and Survival Analysis of Plasmablastic Lymphoma in the United States: A SEER and NCDB Analysis. \u003cem\u003eClinical Lymphoma Myeloma and Leukemia\u003c/em\u003e. 2024;24(4):e152-160.\u003c/li\u003e\n\u003cli\u003eTchernonog E, Faurie P, Coppo P, et al. Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group.\u003cem\u003e Annals of Oncology\u003c/em\u003e. 2017;28(4):843-848.\u003c/li\u003e\n\u003cli\u003eCastillo JJ, Guerrero‐Garcia T, Baldini F, et al. Bortezomib plus EPOCH is effective as frontline treatment in patients with plasmablastic lymphoma. \u003cem\u003eBritish journal of haematology.\u003c/em\u003e 2019;184(4):679-682.\u003c/li\u003e\n\u003cli\u003eCastillo JJ, Winer ES, Stachurski D, et al. Prognostic factors in chemotherapy-treated patients with HIV-associated plasmablastic lymphoma. \u003cem\u003eThe Oncologist\u003c/em\u003e. 2010;15(3):293-299.\u003c/li\u003e\n\u003cli\u003eNoy A, Barta, SK, Kwon D, et al.Daratumumab with Dose-Adjusted EPOCH Is Feasible in Newly Diagnosed Plasmablastic Lymphoma: AIDS Malignancy Consortium 105. \u003cem\u003eBlood. \u003c/em\u003e2024;144(Supplement 1):870.\u003c/li\u003e\n\u003cli\u003eRyu, YK, Ricker, EC, Soderquist CR, et al. Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma. \u003cem\u003eJ. Clin. Med\u003c/em\u003e. 2022(11): 4928.\u003c/li\u003e\n\u003cli\u003eNCCN guidelines version 3.2024. HIV-related B-cell lymphomas. Accessed October 17, 2024. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf\u003c/li\u003e\n\u003cli\u003eDi Ciaccio PR, Polizzotto MN, Cwynarski K, et al. The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma. \u003cem\u003eBlood\u003c/em\u003e. 2024;143(2):152-165.\u003c/li\u003e\n\u003cli\u003eCastillo JJ, Furman M, Beltr\u0026aacute;n BE, et al. Human immunodeficiency virus‐associated plasmablastic lymphoma: poor prognosis in the era of highly active antiretroviral therapy. \u003cem\u003eCancer\u003c/em\u003e. 2012;118(21):5270-5277.\u003c/li\u003e\n\u003cli\u003eSwerdlow SH, Campo E, Harris NL, et al. \u003cem\u003eWHO Classification of Tumours of Haematopoietic and Lymphoid tissues. \u003c/em\u003eIARC; 2017.\u003c/li\u003e\n\u003cli\u003eMcCaffrey DF, Ridgeway G, Morral AR. Propensity score estimation with boosted regression for evaluating causal effects in observational studies. \u003cem\u003ePsychological Methods. \u003c/em\u003e2004; 9(4):403\u0026ndash;425.\u003c/li\u003e\n\u003cli\u003eRidgeway G, McCaffrey D, Morral A, et al. Toolkit for Weighting and Analysis of Nonequivalent Groups: A Tutorial for the Twang Package. \u003c/li\u003e\n\u003cli\u003eRaghunathan TE, Lepkowski JM, Van Hoewyk J, et al. A Multivariate Technique for Multiply Imputing Missing Values Using a Sequence of Regression Models. \u003cem\u003eSurvey methodology\u003c/em\u003e. 2001;27(1):85-95.\u003c/li\u003e\n\u003cli\u003eInternational Non-Hodgkin\u0026apos;s Lymphoma Prognostic Factors Project, \u0026quot;A Predictive Model for Aggressive Non-Hodgkin\u0026apos;s Lymphoma.\u0026quot; New England Journal of Medicine, vol. 329, no. 14, 1993, pp. 987-994.\u003c/li\u003e\n\u003cli\u003eJessa R, Chien N, Villa D, et al. Clinicopathological characteristics and long-term outcomes of plasmablastic lymphoma in British Columbia. Br J Haematol. 2022;199: 230-238.\u003c/li\u003e\n\u003cli\u003eWitte HM, Hertel N, Merz H, et al. Clinicopathological characteristics and MYC status determine treatment outcome in plasmablastic lymphoma: a multicenter study of 76 consecutive patients. Blood Cancer J. 2020;10: 63.\u003c/li\u003e\n\u003cli\u003eThomas N, Dreval K, Gerhard DS, et al. Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma. \u003cem\u003eBlood. \u003c/em\u003e2023;141(8): 904\u0026ndash;916.\u003c/li\u003e\n\u003cli\u003eRadkiewicz C, Bruchfeld JB, Weibull CE, et al. Sex differences in lymphoma incidence and mortality by subtype: A population-based study. Am J Hematol. 2023;98(1):23-30.\u003c/li\u003e\n\u003cli\u003ePfreundschuh M. Age and sex in non-Hodgkin lymphoma therapy: it\u0026apos;s not all created equal, or is it?. American Society of Clinical Oncology Educational Book. 2017;37:505-11.\u003c/li\u003e\n\u003cli\u003eBarta SK, Xue X, Wang D, et al. Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients. Blood. 2013;122(19):3251-62.\u003c/li\u003e\n\u003cli\u003eTchernonog E, Faurie P, Coppo P, et al. Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group. Annals of Oncology. 2017;28(4):843-848.\u003c/li\u003e\n\u003cli\u003eA Multicenter, Open-Label Feasibility Study of Daratumumab With Dose-Adjusted EPOCH in Newly Diagnosed Plasmablastic Lymphoma With or Without HIV. \u003c/li\u003e\n\u003cli\u003eStudy to Evaluate Combined Treatment of Daratumumab, Bortezomib and Dexamethasone in PBL Patients\u003c/li\u003e\n\u003cli\u003eKlanova M, Sehn LH, Bence-Bruckler I, et al. Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL. \u003cem\u003eBlood\u003c/em\u003e. 2019;133(9):919-926.\u003c/li\u003e\n\u003cli\u003eVictor Manuel Orellana-Noia VM, Reed DR, McCook AA, et al. Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions. \u003cem\u003eBlood. \u003c/em\u003e2022;139(3):413\u0026ndash;423.\u003c/li\u003e\n\u003cli\u003eDittus C, Miller JA, Wehbie R, Castillo JJ. Daratumumab with ifosfamide, carboplatin and etoposide for the treatment of relapsed plasmablastic lymphoma. Br J Haematol. 2022;198: e32-e34.\u003c/li\u003e\n\u003cli\u003eCheng L, Song Q, Liu M, et al. Case report: successful management of a refractory plasmablastic lymphoma patient with tislelizumab and lenalidomide. Front Immunol. 2021; 12:702593.\u003c/li\u003e\n\u003cli\u003eMarrero WD, Cruz-Chacon A, Castillo C, Cabanillas F. Successful use of bortezomib-lenalidomide combination as treatment for a patient with plasmablastic lymphoma. Clin Lymphoma Myeloma Leuk. 2018; 18: e275-e277.\u003c/li\u003e\n\u003cli\u003eAndo K, Imaizumi Y, Kobayashi Y, et al. Bortezomib- and Lenalidomide-Based Treatment of Refractory Plasmablastic Lymphoma. Oncol Res Treat. 2020;43(3):112-116.\u003c/li\u003e\n\u003cli\u003eRaychaudhuri R, Qualtieri J, and Garfall AL. Axicabtagene ciloleucel for CD19+ plasmablastic lymphoma. Am J Hematol. 2020;95:E28-E30.\u003c/li\u003e\n\u003cli\u003eRaghunandan S, Pauly M, Blum WG, et al. BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma. J Immunother Cancer. 2023;11(5):e006684.\u003c/li\u003e\n\u003cli\u003eFeng S, Xiong Y, Liu W, et al. BCMA CAR-T induces complete and durable remission in plasmablastic lymphoma synchronous transformation of chronic lymphocytic leukemia: Case report and literature review. Crit Rev Oncol Hematol. 2025;205:104551.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cu\u003eTable 1. Patient Characteristics, Clinical Presentation, and Treatment Patterns by Immune Status Cohort\u003c/u\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 344 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIV-PBL\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 164 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTLD-PBL\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 19 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOIS-PBL\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 36 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC-PBL\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 125 (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep-value*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis (y)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003cp\u003e\u0026lt; 60\u003c/p\u003e\n \u003cp\u003e\u0026ge; 60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e53 (19-91)\u003c/p\u003e\n \u003cp\u003e212 (62)\u003c/p\u003e\n \u003cp\u003e132 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46 (19-76)\u003c/p\u003e\n \u003cp\u003e150 (91)\u003c/p\u003e\n \u003cp\u003e14 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e55 (23-75)\u003c/p\u003e\n \u003cp\u003e11 (58)\u003c/p\u003e\n \u003cp\u003e8 (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67 (21-88)\u003c/p\u003e\n \u003cp\u003e10 (28)\u003c/p\u003e\n \u003cp\u003e26 (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e68 (20-91)\u003c/p\u003e\n \u003cp\u003e41 (33)\u003c/p\u003e\n \u003cp\u003e84 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e270 (78)\u003c/p\u003e\n \u003cp\u003e74 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e141 (86)\u003c/p\u003e\n \u003cp\u003e23 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (68)\u003cbr\u003e\u0026nbsp;6 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (61)\u003cbr\u003e\u0026nbsp;14 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e94 (75)\u003c/p\u003e\n \u003cp\u003e31 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYear of diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e2005-2009\u003c/p\u003e\n \u003cp\u003e2010-2014\u003c/p\u003e\n \u003cp\u003e2015-2019\u003c/p\u003e\n \u003cp\u003e2020-2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29 (8)\u003c/p\u003e\n \u003cp\u003e75 (22)\u003c/p\u003e\n \u003cp\u003e158 (46)\u003c/p\u003e\n \u003cp\u003e82 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (14)\u003c/p\u003e\n \u003cp\u003e40 (24)\u003c/p\u003e\n \u003cp\u003e75 (46)\u003c/p\u003e\n \u003cp\u003e26 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e6 (32)\u003c/p\u003e\n \u003cp\u003e7 (36)\u003c/p\u003e\n \u003cp\u003e6 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003cp\u003e5 (14)\u003c/p\u003e\n \u003cp\u003e15 (42)\u003cbr\u003e\u0026nbsp;14 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (3)\u003c/p\u003e\n \u003cp\u003e24 (19)\u003cbr\u003e\u0026nbsp;61 (49)\u003c/p\u003e\n \u003cp\u003e36 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003cp\u003eBlack / African American\u003c/p\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e230 (67)\u003c/p\u003e\n \u003cp\u003e59 (17)\u003c/p\u003e\n \u003cp\u003e34 (10)\u003c/p\u003e\n \u003cp\u003e21 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e90 (55)\u003c/p\u003e\n \u003cp\u003e44 (27)\u003c/p\u003e\n \u003cp\u003e23 (14)\u003c/p\u003e\n \u003cp\u003e7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (85)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (77)\u003c/p\u003e\n \u003cp\u003e5 (14)\u003c/p\u003e\n \u003cp\u003e1 (3)\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e96 (77)\u003c/p\u003e\n \u003cp\u003e9 (7)\u003c/p\u003e\n \u003cp\u003e9 (7)\u003c/p\u003e\n \u003cp\u003e11 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHispanic/Latino\u003c/p\u003e\n \u003cp\u003eNon-Hispanic/Latino\u003c/p\u003e\n \u003cp\u003eOther/Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e114 (33)\u003c/p\u003e\n \u003cp\u003e206 (60)\u003c/p\u003e\n \u003cp\u003e24 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62 (38)\u003c/p\u003e\n \u003cp\u003e94 (57)\u003c/p\u003e\n \u003cp\u003e8 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e16 (84)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (36)\u003c/p\u003e\n \u003cp\u003e19 (53)\u003c/p\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37 (30)\u003c/p\u003e\n \u003cp\u003e77 (62)\u003c/p\u003e\n \u003cp\u003e11 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eECOG Performance Status\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026le; 1\u003c/p\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e227 (66)\u003c/p\u003e\n \u003cp\u003e74 (22)\u003c/p\u003e\n \u003cp\u003e43 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e104 (64)\u003c/p\u003e\n \u003cp\u003e35 (21)\u003c/p\u003e\n \u003cp\u003e25 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (68)\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e4 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (69)\u003c/p\u003e\n \u003cp\u003e9 (25)\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e85 (68)\u003c/p\u003e\n \u003cp\u003e28 (22)\u003c/p\u003e\n \u003cp\u003e12 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.773\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnn Arbor Stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52 (15)\u003c/p\u003e\n \u003cp\u003e33 (10)\u003c/p\u003e\n \u003cp\u003e22 (6)\u003c/p\u003e\n \u003cp\u003e227 (66)\u003c/p\u003e\n \u003cp\u003e10 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (9)\u003c/p\u003e\n \u003cp\u003e18 (11)\u003c/p\u003e\n \u003cp\u003e13 (8)\u003c/p\u003e\n \u003cp\u003e114 (70)\u003c/p\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (21)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e13 (68)\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (16)\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003cp\u003e24 (67)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (22)\u003c/p\u003e\n \u003cp\u003e13 (10)\u003c/p\u003e\n \u003cp\u003e5 (4)\u003c/p\u003e\n \u003cp\u003e76 (61)\u003c/p\u003e\n \u003cp\u003e4 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNodal Disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e215 (63)\u003c/p\u003e\n \u003cp\u003e112 (33)\u003c/p\u003e\n \u003cp\u003e17 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e112 (68)\u003c/p\u003e\n \u003cp\u003e44 (27)\u003c/p\u003e\n \u003cp\u003e8 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (42)\u003c/p\u003e\n \u003cp\u003e11 (58)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (64)\u003c/p\u003e\n \u003cp\u003e13 (36)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e72 (58)\u003c/p\u003e\n \u003cp\u003e44 (35)\u003c/p\u003e\n \u003cp\u003e9 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.046\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtranodal Disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e316 (92)\u003c/p\u003e\n \u003cp\u003e24 (7)\u003c/p\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e149 (91)\u003c/p\u003e\n \u003cp\u003e12 (7)\u003c/p\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (89)\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (92)\u003c/p\u003e\n \u003cp\u003e3 (8)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e117 (94)\u003c/p\u003e\n \u003cp\u003e7 (5)\u003c/p\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDH Elevation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026gt;1x ULN\u003c/p\u003e\n \u003cp\u003eNot Elevated\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e177 (51)\u003c/p\u003e\n \u003cp\u003e124 (36)\u003c/p\u003e\n \u003cp\u003e43 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e100 (61)\u003c/p\u003e\n \u003cp\u003e48 (29)\u003c/p\u003e\n \u003cp\u003e16 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (37)\u003c/p\u003e\n \u003cp\u003e7 (37)\u003c/p\u003e\n \u003cp\u003e5 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (58)\u003c/p\u003e\n \u003cp\u003e13 (36)\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e49 (39)\u003c/p\u003e\n \u003cp\u003e56 (45)\u003c/p\u003e\n \u003cp\u003e20 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIPI at diagnosis, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e2.51 (1.32)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e2.50 (1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e2.38 (1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e2.88 (1.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e2.42 (1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.423\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMYC\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eRearrangement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45 (13)\u003c/p\u003e\n \u003cp\u003e33 (10)\u003c/p\u003e\n \u003cp\u003e266 (77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (16)\u003c/p\u003e\n \u003cp\u003e9 (5)\u003c/p\u003e\n \u003cp\u003e129 (79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e15 (78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (19)\u003c/p\u003e\n \u003cp\u003e6 (17)\u003c/p\u003e\n \u003cp\u003e23 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (8)\u003c/p\u003e\n \u003cp\u003e16 (13)\u003c/p\u003e\n \u003cp\u003e99 (79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.045\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCNS Involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (3)\u003c/p\u003e\n \u003cp\u003e329 (96)\u003c/p\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (4)\u003c/p\u003e\n \u003cp\u003e155 (95)\u003c/p\u003e\n \u003cp\u003e3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e19 (100)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e36 (100)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (4)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;119 (95)\u003c/p\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.529\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHead/Neck Involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e94 (27)\u003c/p\u003e\n \u003cp\u003e246 (72)\u003c/p\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e53 (32)\u003c/p\u003e\n \u003cp\u003e108 (66)\u003c/p\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e17 (89)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (8)\u003c/p\u003e\n \u003cp\u003e33 (92)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36 (29)\u003c/p\u003e\n \u003cp\u003e88 (70)\u003c/p\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEBV+ by LMP or EBER\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e194 (56)\u003c/p\u003e\n \u003cp\u003e112 (33)\u003c/p\u003e\n \u003cp\u003e38 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (15)\u003c/p\u003e\n \u003cp\u003e118 (72)\u003c/p\u003e\n \u003cp\u003e21 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (26)\u003c/p\u003e\n \u003cp\u003e13 (68)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (64)\u003c/p\u003e\n \u003cp\u003e13 (36)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59 (47)\u003c/p\u003e\n \u003cp\u003e50 (40)\u003c/p\u003e\n \u003cp\u003e16 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemo Regimen in 1L**\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCHOP/CHOP-like\u003c/p\u003e\n \u003cp\u003eEPOCH\u003c/p\u003e\n \u003cp\u003eHyper-CVAD or CODOX-M/IVAC\u003c/p\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44 (14)\u003c/p\u003e\n \u003cp\u003e220 (64)\u003c/p\u003e\n \u003cp\u003e26 (8)\u003c/p\u003e\n \u003cp\u003e19 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (10)\u003c/p\u003e\n \u003cp\u003e110 (67)\u003c/p\u003e\n \u003cp\u003e17 (10)\u003c/p\u003e\n \u003cp\u003e9 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003cp\u003e15 (79)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003cp\u003e1 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (28)\u003c/p\u003e\n \u003cp\u003e19 (53)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (13)\u003c/p\u003e\n \u003cp\u003e76 (61)\u003c/p\u003e\n \u003cp\u003e8 (6)\u003c/p\u003e\n \u003cp\u003e7 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdditional Agents Used in 1L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eProteasome Inhibitor\u003c/p\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003cp\u003eDaratumumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e105 (31)\u003c/p\u003e\n \u003cp\u003e60 (17)\u003c/p\u003e\n \u003cp\u003e12 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47 (29)\u003c/p\u003e\n \u003cp\u003e31 (19)\u003c/p\u003e\n \u003cp\u003e7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (26)\u003c/p\u003e\n \u003cp\u003e4 (21)\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (22)\u003c/p\u003e\n \u003cp\u003e11 (31)\u003c/p\u003e\n \u003cp\u003e2 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45 (36)\u003c/p\u003e\n \u003cp\u003e14 (11)\u003c/p\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.028\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCNS PPx in 1L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIT MTX and/or AraC\u003c/p\u003e\n \u003cp\u003eHD MTX\u003c/p\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e90 (26)\u003c/p\u003e\n \u003cp\u003e23 (7)\u003c/p\u003e\n \u003cp\u003e179 (52)\u003c/p\u003e\n \u003cp\u003e52 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 (30)\u003c/p\u003e\n \u003cp\u003e16 (10)\u003c/p\u003e\n \u003cp\u003e74 (45)\u003c/p\u003e\n \u003cp\u003e24 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e11 (58)\u003c/p\u003e\n \u003cp\u003e6 (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (14)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e25 (69)\u003c/p\u003e\n \u003cp\u003e6 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (26)\u003c/p\u003e\n \u003cp\u003e7 (6)\u003c/p\u003e\n \u003cp\u003e69 (55)\u003c/p\u003e\n \u003cp\u003e16 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConsolidative RT in 1L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003cbr\u003e\u0026nbsp;No\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e63 (18)\u003c/p\u003e\n \u003cp\u003e270 (78)\u003c/p\u003e\n \u003cp\u003e11 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (13)\u003c/p\u003e\n \u003cp\u003e142 (86)\u003c/p\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (16)\u003c/p\u003e\n \u003cp\u003e14 (74)\u003c/p\u003e\n \u003cp\u003e2 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (17)\u003c/p\u003e\n \u003cp\u003e30 (83)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (26)\u003c/p\u003e\n \u003cp\u003e84 (68)\u003c/p\u003e\n \u003cp\u003e8 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 27.0408%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConsolidative ASCT in 1L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (8)\u003c/p\u003e\n \u003cp\u003e307 (89)\u003c/p\u003e\n \u003cp\u003e10 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.1173%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (8)\u003c/p\u003e\n \u003cp\u003e150 (91)\u003c/p\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.8622%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e17 (89)\u003c/p\u003e\n \u003cp\u003e2 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.5%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (11)\u003c/p\u003e\n \u003cp\u003e32 (89)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.6276%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (8)\u003c/p\u003e\n \u003cp\u003e108 (86)\u003c/p\u003e\n \u003cp\u003e7 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.9898%;\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;*Bolded p-values are statistically significant. P-values do not account for missing data rows. SD = Standard deviation. **More detailed description in Supplemental Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eTable 2. Survival Analysis using multiply imputed data\u003c/u\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRisk Factor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable Analysis, OS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 291px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCox Regression (Multiple Imputation), OS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cu\u003eCohort (vs HIV-PBL)\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003ePTLD-PBL\u003c/p\u003e\n \u003cp\u003eIC-PBL\u003c/p\u003e\n \u003cp\u003eOIS-PBL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.51\u003c/p\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003cp\u003e1.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.82-2.78\u003c/p\u003e\n \u003cp\u003e0.83-1.64\u003c/p\u003e\n \u003cp\u003e0.99-2.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.187\u003c/p\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.91\u003c/p\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.92-3.99\u003c/p\u003e\n \u003cp\u003e0.47-1.37\u003c/p\u003e\n \u003cp\u003e0.49-1.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003cp\u003e0.418\u003c/p\u003e\n \u003cp\u003e0.832\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.01-1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.00-1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eFemale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.08-2.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.84-1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.263\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cu\u003eYear of diagnosis (vs 2005-2009)\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003e2010-2014\u003c/p\u003e\n \u003cp\u003e2015-2019\u003c/p\u003e\n \u003cp\u003e2020-2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.49\u003c/p\u003e\n \u003cp\u003e1.88\u003c/p\u003e\n \u003cp\u003e1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.79-2.81\u003c/p\u003e\n \u003cp\u003e1.02-3.46\u003c/p\u003e\n \u003cp\u003e0.83-3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.220\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003cp\u003e1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.50-2.4\u003c/p\u003e\n \u003cp\u003e0.79-3.41\u003c/p\u003e\n \u003cp\u003e0.67-3.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.817\u003c/p\u003e\n \u003cp\u003e0.180\u003c/p\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cu\u003eRace (vs White)\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eBlack/African American\u003c/p\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.58\u003c/p\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.09-2.30\u003c/p\u003e\n \u003cp\u003e0.24-1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.43\u003c/p\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.91-2.23\u003c/p\u003e\n \u003cp\u003e0.28-1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003cp\u003e0.253\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cu\u003eEthnicity (vs Hispanic/Latino)\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eNon-Hispanic/Latino\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.96-1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.72-1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.717\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eECOG 2+ (vs \u0026lt;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e2.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.82-3.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.14-3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eStage III/IV (vs I/II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.64-3.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.02-3.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.043\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eExtranodal disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.16-2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.84-1.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eLDH elevation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e3.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e2.12-4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e2.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.65-4.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eIPI (per one point increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.25-1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.84-1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cem\u003eMYC\u0026nbsp;\u003c/em\u003erearrangement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.27-6.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.26-6.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.761\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eEBV+ by either LMP1 or EBER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.42-0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.46-1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cu\u003e1L Regimen (vs CHOP)\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eEPOCH\u003c/p\u003e\n \u003cp\u003eHigh-Intensity\u003c/p\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.49-1.21\u003c/p\u003e\n \u003cp\u003e0.52-1.97\u003c/p\u003e\n \u003cp\u003e0.64-2.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003cp\u003e0.983\u003c/p\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003cp\u003e1.36\u003c/p\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.39-1.07\u003c/p\u003e\n \u003cp\u003e0.62-3.01\u003c/p\u003e\n \u003cp\u003e0.43-1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003cp\u003e0.444\u003c/p\u003e\n \u003cp\u003e0.742\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003ePI in 1L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.76-1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e0.766\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.68-1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.950\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003e\u003cu\u003eCNS PPx (vs none)\u003c/u\u003e\u003c/p\u003e\n \u003cp\u003eIT MTX/AraC\u003c/p\u003e\n \u003cp\u003eHD IV MTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.52-1.10\u003c/p\u003e\n \u003cp\u003e0.50-1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.51-1.28\u003c/p\u003e\n \u003cp\u003e0.34-1.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.363\u003c/p\u003e\n \u003cp\u003e0.295\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 242px;\"\u003e\n \u003cp\u003eConsolidative RT in 1L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.38-0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.57-1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 97px;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Bolded p-values are statistically significant\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"blood-cancer-journal","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bcj","sideBox":"Learn more about [Blood Cancer Journal](http://www.nature.com/bcj/)","snPcode":"41408","submissionUrl":"https://mts-bcj.nature.com/cgi-bin/main.plex","title":"Blood Cancer Journal","twitterHandle":"@bloodcancerjnl","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7607922/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7607922/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePlasmablastic lymphoma (PBL) is a rare, aggressive AIDS-related lymphoma observed in patients with immunosuppressed states as well as in immunocompetent individuals. We sought to determine survival outcomes, prognostic factors, and optimal treatment regimens in a large, contemporary cohort of patients with PBL in the United States. We performed a multicenter, retrospective cohort study, including 344 patients diagnosed with PBL between 2005 and 2022. Patients were stratified into cohorts according to underlying immune status. Survival outcomes were calculated using Kaplan-Meier statistics, with cohort-specific survival outcomes adjusted using propensity score-based weighting. Factors associated with outcomes were assessed via multivariable models using multiple imputation. The median age at diagnosis was 53 years, most patients were male (n\u0026thinsp;=\u0026thinsp;270), and many had HIV (n\u0026thinsp;=\u0026thinsp;164). The median OS was 5.0 years, with a median PFS of 1.4 years. Patients living with HIV had the best outcomes, whereas patients with prior organ transplantation had the worst outcomes. Use of higher intensity chemotherapy regimens and use of a proteasome inhibitor in the frontline setting did not show survival benefit. While there was no clear optimal treatment approach in the frontline setting, the median OS of 5.0 years is dramatically improved compared with historical controls.\u003c/p\u003e","manuscriptTitle":"Prognosis and Treatment of Plasmablastic Lymphoma in the United States: A Multicenter Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-30 12:22:54","doi":"10.21203/rs.3.rs-7607922/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-10-14T15:12:57+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-13T07:08:07+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-09-26T11:45:53+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-09-19T06:50:23+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-09-19T04:19:48+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-09-18T21:05:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T14:47:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-16T14:47:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Blood Cancer Journal","date":"2025-09-13T14:18:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"blood-cancer-journal","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bcj","sideBox":"Learn more about [Blood Cancer Journal](http://www.nature.com/bcj/)","snPcode":"41408","submissionUrl":"https://mts-bcj.nature.com/cgi-bin/main.plex","title":"Blood Cancer Journal","twitterHandle":"@bloodcancerjnl","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3ffea211-24be-41fc-b9cd-e7a84ba5d288","owner":[],"postedDate":"September 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":54971133,"name":"Health sciences/Diseases/Haematological diseases/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/B-cell lymphoma"},{"id":54971134,"name":"Biological sciences/Cancer/Haematological cancer/Lymphoma"}],"tags":[],"updatedAt":"2026-03-28T07:09:16+00:00","versionOfRecord":{"articleIdentity":"rs-7607922","link":"https://doi.org/10.1038/s41408-026-01457-3","journal":{"identity":"blood-cancer-journal","isVorOnly":false,"title":"Blood Cancer Journal"},"publishedOn":"2026-03-23 04:00:00","publishedOnDateReadable":"March 23rd, 2026"},"versionCreatedAt":"2025-09-30 12:22:54","video":"","vorDoi":"10.1038/s41408-026-01457-3","vorDoiUrl":"https://doi.org/10.1038/s41408-026-01457-3","workflowStages":[]},"version":"v1","identity":"rs-7607922","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7607922","identity":"rs-7607922","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}