Clinical characteristics and prognosis analysis of 13 cases of newly diagnosed plasmablastic lymphoma

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Methods The clinical data of 13 newly diagnosed PBL patients admitted to Chongqing University Cancer Hospital from January 2013 to June 2024 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier survival curve and Log-rank test. Univariate and multivariate Cox regression model analyses were used for analyzing prognostic factors. Results ①The number of male and female cases was 10:3. The median age was 52.15 (26-78) years old. Six cases (46.1%) had extranodal organ involvement as the initial symptom, including 3 cases (23.1%) of oral and maxillofacial region. There were 7 cases (53.9%) in Ann-Arbor stage Ⅰ~Ⅱ and 6 cases (46.1%) in stage Ⅳ. Six cases (46.1%) had B symptoms. Two cases (15.3%) had an IPI score ≥3. Nine cases (69.2%) had elevated peripheral blood EB-DNA detection. One case had bone marrow invasion (7.7%), and one case had central nervous system invasion. ②All patients expressed CD38, CD138, and MUM-1. B-cell markers such as PAX-5 and Bcl-6 were occasionally seen. Six cases (46.2%) had positive EBER detection. ③All 13 patients received chemotherapy, and 3 cases received combined radiotherapy. The median follow-up was 48.31 (16-141) months. The median OS was 33.08 (11-79) months, and the median PFS was 25.62 (2-79) months. ④Seven cases received the EPOCH regimen, 6 cases received the CHOP or CHOP-like regimen. Five cases received new drugs in the first-line treatment (3 cases combined with bortezomib, 1 case combined with lenalidomide, and 1 case combined with a PD-1 inhibitor). Three cases received combined local radiotherapy. After first-line treatment, 5 cases had a CR evaluation, 6 cases had a PR evaluation, 1 case had SD, and 1 case had NA. ⑤The best efficacy evaluation: 5 cases had CR, 7 cases had PR, and 1 case had NA. The combination of new drugs and autologous stem cell transplantation (ASCT) in the first-line treatment had obvious benefits, but the use of new drugs such as Lenalidomide and Selinexor in the third-line and above had poor effects. ⑥Kaplan-Meier analysis showed that the overall survival of PBL was significantly related to IPI score 3-5, B symptoms, and male gender (P<0.05). According to univariate COX regression analysis, for newly diagnosed PBL, anemia (≤120g/L) and IPI score 3-5 were factors for poor prognosis of PFS. IPI score 3-5 was a factor for poor prognosis of OS. Combined HIV infection had no significant impact on prognosis. Conclusions For PBL treated through standardized treatment, the impact of HIV infection on prognosis can be overcome. At initial diagnosis, anemia (≤120g/L) and IPI score 3-5 are factors for poor prognosis of PFS in PBL. IPI score 3-5 is a factor for poor prognosis of OS. The first-line treatment choice of combining new drugs (Bortezomib, Lenalidomide, PD-1 inhibitor) and ASCT is expected to improve the prognosis of PBL. analysis plasmablastic lymphoma Figures Figure 1 Background Plasmablastic lymphoma (PBL) is a malignant tumor derived from plasma cells. It has characteristics such as low incidence, high malignancy, easy drug resistance, poor prognosis, and high recurrence rate [ 1 ] . Currently, there is no standard treatment regimen for PBL. Centers mainly use medium to high-intensity chemotherapy [ 2 ] . The NCCN guidelines [ 3 ] recommend regimens with higher intensity than CHOP. Commonly used regimens refer to HIV-related lymphomas [ 4 ] , including the EPOCH regimen, hyper-CVAD-MA regimen, CODOX-M/IVAC regimen, etc., but the effects are not satisfactory. Now, the clinical characteristics, treatment, and outcomes of 13 PBL patients diagnosed and treated in our center are summarized as follows, and a literature review is conducted to provide reference for clinicians. Method Data of clinicians 13 newly diagnosed PBL patients confirmed in Chongqing University Cancer Hospital from January 2013 to June 2024 were taken as the research objects. The clinical and follow-up data of the patients were retrospectively analyzed, including demographic data, epidemiological data, clinical characteristics, international prognostic index, staging, serum HIV antibody detection, serum EBV-DNA detection, diagnosis and treatment process (chemotherapy regimen and chemotherapy cycle, radiotherapy, stem cell transplantation, treatment-related complications), efficacy, and follow-up time. Diagnosis The pathological diagnosis of PBL all met the 2024 WHO classification standard for lymphohematopoietic system. It was first diagnosed by the pathologists in our hospital or confirmed after pathological consultation. The diagnosis of AIDS met the AIDS diagnosis and treatment guidelines issued by the Chinese Medical Association in 2011. Positive HIV-1 antibody was confirmed by the AIDS diagnosis laboratory of Chongqing and various municipal centers for disease control and prevention using the unified national confirmation method - immunoblotting. Efficacy Evaluation and Survival Definition The judgment criteria for efficacy evaluation of enhanced CT are based on the revised standards of Cheson in 2014 [5] . The efficacy evaluation criteria for PET-CT are based on the revised standards of Cheson in 2007 [6] , including complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). The overall survival (OS) period is defined as the time from diagnosis to death or the last follow-up. The progression-free survival (PFS) period is defined as the time from diagnosis to disease progression or the last follow-up. Results Clinical Characteristics (Table 1) Among the 13 PBL patients, 7 were HIV-positive, all male, with a median age of 50 (26-66) years old; 6 were HIV-negative, with 3 males and 3 females, and a median age of 53.5 (32-78) years old. In the HIV-positive group, 2 cases had extranodal invasion (gingiva and oropharynx respectively), and in the HIV-negative group, 4 cases had extranodal involvement (1 case of oral cavity, 1 case of testis, 1 case of bone marrow and central nervous system, and 1 case of bone and kidney). There were 4 cases with B symptoms (4/13, 66.7%). Ann-Arbor staging: stage I (2/13, 15.4%), stage II (5/13, 38.5%), stage III (0), stage IV (6/13, 46.2%). IPI score: 0-1 points (8/13, 61.5%), ≥2 points (5/13, 38.5%). Laboratory tests: anemia (HB≤120 g/L) in 4 cases (4/13, 66.7%), elevated LDH (≥250 U/L) in 8 cases (8/13, 61.5%), elevated beta-2 microglobulin (≥5.5 g/L) in 11 cases (11/13, 84.6%), and elevated peripheral blood EBV-DNA in 9 cases (9/13, 69.2%). Histopathological and Immunohistochemical Characteristics (Table 2):Pathological specimens were all stained with HE and analyzed by immunohistochemical staining. They were all diffusely growing large cells. The immunophenotype mainly expressed plasma cell markers such as CD38 (10/13, 76.9%), CD138 (6/13, 46.2%), and MUM-1 was positive. B-cell markers CD20, CD10, PAX-5, and BCL6 were rare. There were 4 cases with positive expression of BCL2. The median Ki67 was 80% (30-90%), and EBER was positive in 6 cases (6/13, 46.2%). Treatment and Outcome All 13 patients received chemotherapy. In the HIV-negative group of 6 cases: first-line regimens: CHOP/CHOPE regimen (cyclophosphamide, epirubicin, vindesine, prednisone, etoposide) in 3 cases (3/6, 50.0%), CAP regimen (cyclophosphamide, epirubicin, prednisone) combined with bortezomib in 1 case (1/6, 16.7%); EPOCH regimen (etoposide, dexamethasone, cyclophosphamide, epirubicin, vindesine) in 1 case (1/6, 16.7%), EPOCH regimen combined with bortezomib in 1 case (1/6, 16.7%). Efficacy evaluation: 2 cases of CR (2/6, 33.3%), 2 cases of PR (2/6, 33.3%), 1 case of PD (1/6, 16.7%). Case 5 was abandoned due to advanced age and intolerance, and the evaluation was NA (1/6, 16.7%). Patients based on the EPOCH regimen all achieved PR or CR. Among patients based on the CHOP regimen, 2 cases (2/3, 66.7%) achieved PR and 1 case had PD. There were 2 cases (2/6, 33.3%) who received combined radiotherapy (ratiotherapy, RT) in the first-line chemotherapy. Patient 1 received the CHOP combined with lenalidomide regimen and ASCT as second-line treatment , and the efficacy evaluation was PR. However, the disease progressed quickly. After the third-line treatment with bortezomib combined with GDP (gemcitabine, dexamethasone, nedaplatin) and XPO1 inhibitor, the disease deteriorated again and the patient died. Patient 6 changed to the MTX regimen combined with autologous hematopoietic stem cell transplantation, and continuous PR was achieved. Currently, the patient is still alive. In the HIV-positive group of 7 cases: 4 cases received the EPOCH regimen in the first line, 1 case received the EPOCH regimen combined with PD-1 inhibitor, 1 case received the CHOP regimen combined with lenalidomide, and 1 case received the CAP regimen combined with bortezomib. After first-line treatment, the efficacy evaluation was: 3 cases of CR and 4 cases of PR. Among the 2 cases of CR patients, they received autologous hematopoietic stem cell transplantation and achieved a continuous CR state. Patient 8 achieved PR after first-line treatment but gave up treatment due to personal reasons. After half a year, the disease progressed and the patient died. The rest of the patients are all alive. Second-line regimen: Patient 7 received local radiotherapy and maintained PR; Patient 12 was changed to the EPOCH regimen combined with autologous hematopoietic stem cell transplantation, and the efficacy changed from PR to CR. Patient 9 was maintained with bortezomib, and currently the efficacy is continuously CR. Among the 13 patients, 4 cases (4/13, 57.1%) received prophylactic intrathecal injection. In 1 case (Patient 6), abnormal cells were found in the cerebrospinal fluid, and considering tumor, after intravenous treatment with HD-MTX, the cerebrospinal fluid turned negative, and regular maintenance treatment with PD-1 inhibitor was given. After standardized treatment, 4 cases relapsed. Among them, 3 cases received second-line regimen treatment (including autologous hematopoietic stem cell transplantation) again and achieved CR/PR. Five patients died (4 cases were HIV-negative and 1 case was HIV-positive. One case was intolerant due to advanced age (78 years old), one case gave up treatment due to personal reasons, and 4 cases died due to disease progression). Currently, there are a total of 8 surviving patients (2 HIV-positive cases and 6 HIV-negative cases), and 4 cases have the best efficacy of CR. However, the use of new drugs such as lenalidomide and selinexor in the third-line treatment and above has poor effects. In terms of adverse reactions: mostly grade III or below neurotoxicity and hematological toxicity. One case had incomplete intestinal obstruction, and one case had grade IV thrombocytopenia. After symptomatic and supportive treatment, they recovered, and the overall tolerance was acceptable. The overall median follow-up was 48.31 (16-141) months, the median OS time was 33.08 (11-79) months, and the median PFS time was 25.62 (2-79) months. Prognostic Analysis (Fig 1 and Table 3): Survival curve analysis (Fig 1) shows that IPI score 3-5, B symptoms, and gender have significant differences in the survival time of PBL (P<0.05), and HIV has no significant impact on prognosis. Univariate COX regression analysis (Table 3) shows that for newly diagnosed PBL, anemia (≤120g/L) and IPI score 3-5 are factors for poor prognosis of PFS, and IPI score 3-5 is a factor for poor prognosis of OS. Multivariate COX regression analysis shows that there are no statistically significant indicators Discussion Primary breast lymphoma (PBL) was first reported by Delecluse et al. [7] in 1997 . Qunaj et al. [8] analyzed a total of 481 PBL patients registered in the National Cancer Database of the United States from 2010 to 2013. The patient population accounts for 2% of all HIV-related lymphomas. The mechanism of occurrence may be related to viral infection [9] [10] . In 2024, Ramirez-Gamero et al. [1] found that the population prone to PBL is adult men, with a median age of onset of 55 years. The median age of onset of PBL in HIV-positive patients is 42 years, and most of them are immunodeficient people. In this study, male patients were the majority (10/13, 76.9%), the median age of onset was 52.15 (26-78) years, and the median age of onset in the HIV-positive group was 50 (26-66) years. The median age of 13 cases was consistent with previous reports, and the age of the HIV-positive group was older. Ciaccio et al. [11] reported that negative EBV, bone marrow invasion, and poor physical condition are poor prognostic factors for OS in PBL patients, while HIV infection is not related to OS. In this study, through univariate and multivariate regression analysis, factors for poor prognosis of PFS include anemia (≤120g/L) with an HR of 2.682 and a 95% CI of (1.063-6.764), and HR for relapsed/refractory PBL is 0.305, and the 95% CI is (0.101-0.920). This study also reached the conclusion that HIV is not related to prognosis, suggesting that the existing treatment regimens can overcome the adverse effect of HIV on the overall prognosis. Survival curve analysis shows that IPI scores of 3-5, B symptoms, and male gender have significant differences in the survival time of PBL (P<0.05). Univariate COX regression analysis shows that for newly diagnosed PBL, anemia (≤120g/L) and IPI scores of 3-5 are factors for poor prognosis of PFS. IPI scores of 3-5 are factors for poor prognosis of OS. In general, IPI scores of 3-5 are poor prognostic factors for PBL and have obvious impacts on survival, PFS, and OS. The pathogenesis of PBL is unknown. Castillo et al. [12] found that the positive rate of EBER in HIV-negative PBL patients is lower than that in HIV-positive PBL patients (50% vs. 75%). Therefore, it is speculated that the pathogenesis of PBL may be related to EBV infection. In this study, there were 9 cases (9/13, 69.2%) of elevated EBV-DNA in the peripheral blood of PBL patients. Pathological HE staining showed diffuse proliferation of large tumor cells. The immunophenotype expressed plasma cell markers such as CD38, CD138, and Mum-1, while B cell markers CD20, CD10, PAX-5, and BCL-6 were rare. T cell marker CD3 was all negative. The median Ki-67 was 80% (30-90%), and EBER was positive (6/13, 46.2%). There is no standard treatment regimen for PBL. Traditional regimens used by various centers [4] include: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens, EPOCH (etoposide, vincristine, cyclophosphamide, doxorubicin, prednisone), hyper-CVAD-MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone, and high-dose methotrexate and cytarabine), CODOX-M/IVAC (cyclophosphamide, adriamycin, vincristine, methotrexate/isofosfamide, cytarabine, etoposide), etc. New regimens include: combination with bortezomib [13] , lenalidomide [14] , thalidomide [15] , PD-1 inhibitor [16] , ASCT [17] , CAR-T, etc. In this study, 13 patients all received standardized chemotherapy. Among them, 7 patients received the EPOCH regimen, 6 patients received CHOP or CHOP-like regimens, 5 patients received new drugs in the first line (3 cases combined with bortezomib, 1 case combined with lenalidomide, and 1 case combined with PD-1), and 3 cases combined with local radiotherapy. Except for 1 case who gave up treatment due to intolerance to toxic and side effects at an advanced age, and 1 case who refused to continue treatment due to personal reasons. After first-line treatment, 3 of the 11 patients had a response evaluation of CR, 6 cases had PR, 1 case had SD, and 1 case had PD. One case received a second-line regimen combined with autologous hematopoietic stem cell transplantation, and the efficacy reached CR from PR, but the disease relapsed quickly and the patient died. One case achieved PR after successively receiving the GDP regimen, DICE regimen, and DHAP regimen. One case achieved PR after receiving the MTX regimen combined with autologous hematopoietic stem cell transplantation. The best efficacy evaluation: 5 cases of CR, 6 cases of PR, 1 case of SD, and 1 case of NA. A total of 5 patients died, 2 died due to giving up treatment, and 3 died due to disease progression. According to relevant literature statistics [18] [19] [20] , the median overall survival of PBL patients is 15 months, and the 3-year OS rate is 25%. Castillo JJ et al. [21] reported that the median OS of HIV-positive and negative PBL patients is 3 months and 4 months, respectively. In this study, the median OS time of PBL is 33.08 (11-79) months, which is significantly longer than previous reports, and there is no significant difference between the HIV-positive group and the negative group. This suggests that PBL first-line treatment combined with new drugs including bortezomib, lenalidomide, PD-1 inhibitor, RT, ASCT, etc. can effectively prolong survival. Conclusions In conclusion, the data in this paper show that PBL is highly invasive, extranodal involvement is common, and it is prone to recurrence. A high IPI score is a poor prognostic indicator for PBL. After standardized anti-tumor treatment, the overall survival rate is significantly improved compared with previous reports, and it can overcome the adverse effect of HIV on prognosis. The treatment regimen is based on traditional regimens such as CHOP or EPOCH, combined with new drugs such as bortezomib, lenalidomide, or PD-1 inhibitor, combined with ASCT, which may improve the overall survival rate. However, this study is a retrospective analysis, and the number of cases is limited. Further multi-center, prospective studies are needed for further exploration. Declarations Funding This study was funded by Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX1150), Fundamental Research Funds for the Central Universities (2022CDJYGRH-001) and Chongqing Professional Talents Plan (cstc2022ycjh-bgzxm0048). AUTHOR CONTRIBUTIONS J.P.L.,,Y.L. were responsible for the conception and design of the study. D.H.H.,, Y.X,, Q.Y.L.,, Y.Y.N, were responsible for participant recruitment. Q.Q., Y.X., J.Y.L., were responsible for participant follow-up and clinical data acquisition. J.L.,Z.L.Y., C.L.H., L.X.X., T.T.L., were responsible for Sample testing and data acquisition. B.L.G., were responsible for manuscript writing and revision. All authors read and approved the final manuscript. DECLARATION OF COMPETING INTEREST The authors declare that they have no competing interests. AVAILABILITY OF DATA AND MATERIALS Data are available from the corresponding author on reasonable request. ETHICS APPROVAL AND CONSENT TO PARTICIPATE This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the local research ethics committee of the Chongqing University Cancer Hospital. The requirement for informed consent was waived by the Institutional Review Board because of the study’s retrospective nature. References Ramirez-Gamero A, Martínez-Cordero H, Beltrán BE, et al. 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Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma[J]. Leuk Lymphoma, 2010,51（11）:2047-2053. doi: 10.3109/10428194.2010.516040 . Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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09:53:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5917684/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5917684/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":76193465,"identity":"227138e9-2ccc-4346-8529-b929edca15ab","added_by":"auto","created_at":"2025-02-13 09:58:42","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":149941,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelation analysis of overall survival and IPI, extranodal invasion, and age by Kaplan-Meier method\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5917684/v1/cddef76dfa6a896962451ab5.jpeg"},{"id":76413360,"identity":"6f8b3a55-4a7a-4988-97d0-91edf976b009","added_by":"auto","created_at":"2025-02-17 02:01:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":674726,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5917684/v1/b3e453b9-8f4f-49b5-a050-99e9fa7cbca3.pdf"},{"id":76193460,"identity":"b3000cc7-eaf8-4f18-bd8d-4662978ed33b","added_by":"auto","created_at":"2025-02-13 09:58:42","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":55530,"visible":true,"origin":"","legend":"","description":"","filename":"Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-5917684/v1/3739a582f218606e28210d84.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical characteristics and prognosis analysis of 13 cases of newly diagnosed plasmablastic lymphoma","fulltext":[{"header":"Background","content":"\u003cp\u003ePlasmablastic lymphoma (PBL) is a malignant tumor derived from plasma cells. It has characteristics such as low incidence, high malignancy, easy drug resistance, poor prognosis, and high recurrence rate \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Currently, there is no standard treatment regimen for PBL. Centers mainly use medium to high-intensity chemotherapy \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The NCCN guidelines \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003erecommend regimens with higher intensity than CHOP. Commonly used regimens refer to HIV-related lymphomas \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, including the EPOCH regimen, hyper-CVAD-MA regimen, CODOX-M/IVAC regimen, etc., but the effects are not satisfactory. Now, the clinical characteristics, treatment, and outcomes of 13 PBL patients diagnosed and treated in our center are summarized as follows, and a literature review is conducted to provide reference for clinicians.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e\u003cstrong\u003eData of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eclinicians\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e13 newly diagnosed PBL patients confirmed in Chongqing University Cancer Hospital from January 2013 to June 2024 were taken as the research objects. The clinical and follow-up data of the patients were retrospectively analyzed, including demographic data, epidemiological data, clinical characteristics, international prognostic index, staging, serum HIV antibody detection, serum EBV-DNA detection, diagnosis and treatment process (chemotherapy regimen and chemotherapy cycle, radiotherapy, stem cell transplantation, treatment-related complications), efficacy, and follow-up time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e The pathological diagnosis of PBL all met the 2024 WHO classification standard for lymphohematopoietic system. It was first diagnosed by the pathologists in our hospital or confirmed after pathological consultation. The diagnosis of AIDS met the AIDS diagnosis and treatment guidelines issued by the Chinese Medical Association in 2011. Positive HIV-1 antibody was confirmed by the AIDS diagnosis laboratory of Chongqing and various municipal centers for disease control and prevention using the unified national confirmation method - immunoblotting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEfficacy Evaluation and Survival Definition\u003c/strong\u003e The judgment criteria for efficacy evaluation of enhanced CT are based on the revised standards of Cheson in 2014\u0026nbsp;\u003csup\u003e[5]\u003c/sup\u003e. The efficacy evaluation criteria for PET-CT are based on the revised standards of Cheson in 2007\u0026nbsp;\u003csup\u003e[6]\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e including complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). The overall survival (OS) period is defined as the time from diagnosis to death or the last follow-up. The progression-free survival (PFS) period is defined as the time from diagnosis to disease progression or the last follow-up.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical Characteristics\u003c/strong\u003e (Table 1) Among the 13 PBL patients, 7 were HIV-positive, all male, with a median age of 50 (26-66) years old; 6 were HIV-negative, with 3 males and 3 females, and a median age of 53.5 (32-78) years old. In the HIV-positive group, 2 cases had extranodal invasion (gingiva and oropharynx respectively), and in the HIV-negative group, 4 cases had extranodal involvement (1 case of oral cavity, 1 case of testis, 1 case of bone marrow and central nervous system, and 1 case of bone and kidney). There were 4 cases with B symptoms (4/13, 66.7%). Ann-Arbor staging: stage I (2/13, 15.4%), stage II (5/13, 38.5%), stage III (0), stage IV (6/13, 46.2%). IPI score: 0-1 points (8/13, 61.5%), \u0026ge;2 points (5/13, 38.5%). Laboratory tests: anemia (HB\u0026le;120 g/L) in 4 cases (4/13, 66.7%), elevated LDH (\u0026ge;250 U/L) in 8 cases (8/13, 61.5%), elevated beta-2 microglobulin (\u0026ge;5.5 g/L) in 11 cases (11/13, 84.6%), and elevated peripheral blood EBV-DNA in 9 cases (9/13, 69.2%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological and Immunohistochemical Characteristics\u003c/strong\u003e (Table 2):Pathological specimens were all stained with HE and analyzed by immunohistochemical staining. They were all diffusely growing large cells. The immunophenotype mainly expressed plasma cell markers such as CD38 (10/13, 76.9%), CD138 (6/13, 46.2%), and MUM-1 was positive. B-cell markers CD20, CD10, PAX-5, and BCL6 were rare. There were 4 cases with positive expression of BCL2. The median Ki67 was 80% (30-90%), and EBER was positive in 6 cases (6/13, 46.2%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment and Outcome\u003c/strong\u003e All 13 patients received chemotherapy. In the HIV-negative group of 6 cases: first-line regimens: CHOP/CHOPE regimen (cyclophosphamide, epirubicin, vindesine, prednisone, etoposide) in 3 cases (3/6, 50.0%), CAP regimen (cyclophosphamide, epirubicin, prednisone) combined with bortezomib in 1 case (1/6, 16.7%); EPOCH regimen (etoposide, dexamethasone, cyclophosphamide, epirubicin, vindesine) in 1 case (1/6, 16.7%), EPOCH regimen combined with bortezomib in 1 case (1/6, 16.7%). Efficacy evaluation: 2 cases of CR (2/6, 33.3%), 2 cases of PR (2/6, 33.3%), 1 case of PD (1/6, 16.7%). Case 5 was abandoned due to advanced age and intolerance, and the evaluation was NA (1/6, 16.7%). Patients based on the EPOCH regimen all achieved PR or CR. Among patients based on the CHOP regimen, 2 cases (2/3, 66.7%) achieved PR and 1 case had PD. There were 2 cases (2/6, 33.3%) who received combined radiotherapy (ratiotherapy, RT) in the first-line chemotherapy. Patient 1 received the CHOP combined with lenalidomide regimen and ASCT as second-line treatment , and the efficacy evaluation was PR. However, the disease progressed quickly. After the third-line treatment with bortezomib combined with GDP (gemcitabine, dexamethasone, nedaplatin) and XPO1 inhibitor, the disease deteriorated again and the patient died. Patient 6 changed to the MTX regimen combined with autologous hematopoietic stem cell transplantation, and continuous PR was achieved. Currently, the patient is still alive. In the HIV-positive group of 7 cases: 4 cases received the EPOCH regimen in the first line, 1 case received the EPOCH regimen combined with PD-1 inhibitor, 1 case received the CHOP regimen combined with lenalidomide, and 1 case received the CAP regimen combined with bortezomib. After first-line treatment, the efficacy evaluation was: 3 cases of CR and 4 cases of PR. Among the 2 cases of CR patients, they received autologous hematopoietic stem cell transplantation and achieved a continuous CR state. Patient 8 achieved PR after first-line treatment but gave up treatment due to personal reasons. After half a year, the disease progressed and the patient died. The rest of the patients are all alive. Second-line regimen: Patient 7 received local radiotherapy and maintained PR; Patient 12 was changed to the EPOCH regimen combined with autologous hematopoietic stem cell transplantation, and the efficacy changed from PR to CR. Patient 9 was maintained with bortezomib, and currently the efficacy is continuously CR. Among the 13 patients, 4 cases (4/13, 57.1%) received prophylactic intrathecal injection. In 1 case (Patient 6), abnormal cells were found in the cerebrospinal fluid, and considering tumor, after intravenous treatment with HD-MTX, the cerebrospinal fluid turned negative, and regular maintenance treatment with PD-1 inhibitor was given. After standardized treatment, 4 cases relapsed. Among them, 3 cases received second-line regimen treatment (including autologous hematopoietic stem cell transplantation) again and achieved CR/PR. Five patients died (4 cases were HIV-negative and 1 case was HIV-positive. One case was intolerant due to advanced age (78 years old), one case gave up treatment due to personal reasons, and 4 cases died due to disease progression). Currently, there are a total of 8 surviving patients (2 HIV-positive cases and 6 HIV-negative cases), and 4 cases have the best efficacy of CR. However, the use of new drugs such as lenalidomide and selinexor in the third-line treatment and above has poor effects. In terms of adverse reactions: mostly grade III or below neurotoxicity and hematological toxicity. One case had incomplete intestinal obstruction, and one case had grade IV thrombocytopenia. After symptomatic and supportive treatment, they recovered, and the overall tolerance was acceptable. The overall median follow-up was 48.31 (16-141) months, the median OS time was 33.08 (11-79) months, and the median PFS time was 25.62 (2-79) months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrognostic Analysis\u003c/strong\u003e (Fig 1 and Table 3): Survival curve analysis (Fig 1) shows that IPI score 3-5, B symptoms, and gender have significant differences in the survival time of PBL (P\u0026lt;0.05), and HIV has no significant impact on prognosis. Univariate COX regression analysis (Table 3) shows that for newly diagnosed PBL, anemia (\u0026le;120g/L) and IPI score 3-5 are factors for poor prognosis of PFS, and IPI score 3-5 is a factor for poor prognosis of OS. Multivariate COX regression analysis shows that there are no statistically significant indicators\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary breast lymphoma (PBL) was first reported by Delecluse et al. \u003csup\u003e[7]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003ein 1997 . Qunaj et al. \u003csup\u003e[8]\u003c/sup\u003e analyzed a total of 481 PBL patients registered in the National Cancer Database of the United States from 2010 to 2013. The patient population accounts for 2% of all HIV-related lymphomas. The mechanism of occurrence may be related to viral infection \u003csup\u003e[9]\u003c/sup\u003e\u003csup\u003e[10]\u003c/sup\u003e. In 2024, Ramirez-Gamero et al. \u003csup\u003e[1]\u003c/sup\u003e found that the population prone to PBL is adult men, with a median age of onset of 55 years. The median age of onset of PBL in HIV-positive patients is 42 years, and most of them are immunodeficient people. In this study, male patients were the majority (10/13, 76.9%), the median age of onset was 52.15 (26-78) years, and the median age of onset in the HIV-positive group was 50 (26-66) years. The median age of 13 cases was consistent with previous reports, and the age of the HIV-positive group was older.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCiaccio et al. \u003csup\u003e[11]\u003c/sup\u003e reported that negative EBV, bone marrow invasion, and poor physical condition are poor prognostic factors for OS in PBL patients, while HIV infection is not related to OS. In this study, through univariate and multivariate regression analysis, factors for poor prognosis of PFS include anemia (\u0026le;120g/L) with an HR of 2.682 and a 95% CI of (1.063-6.764), and HR for relapsed/refractory PBL is 0.305, and the 95% CI is (0.101-0.920). This study also reached the conclusion that HIV is not related to prognosis, suggesting that the existing treatment regimens can overcome the adverse effect of HIV on the overall prognosis. Survival curve analysis shows that IPI scores of 3-5, B symptoms, and male gender have significant differences in the survival time of PBL (P\u0026lt;0.05). Univariate COX regression analysis shows that for newly diagnosed PBL, anemia (\u0026le;120g/L) and IPI scores of 3-5 are factors for poor prognosis of PFS. IPI scores of 3-5 are factors for poor prognosis of OS. In general, IPI scores of 3-5 are poor prognostic factors for PBL and have obvious impacts on survival, PFS, and OS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe pathogenesis of PBL is unknown. Castillo et al. [12] found that the positive rate of EBER in HIV-negative PBL patients is lower than that in HIV-positive PBL patients (50% vs. 75%). Therefore, it is speculated that the pathogenesis of PBL may be related to EBV infection. In this study, there were 9 cases (9/13, 69.2%) of elevated EBV-DNA in the peripheral blood of PBL patients. Pathological HE staining showed diffuse proliferation of large tumor cells. The immunophenotype expressed plasma cell markers such as CD38, CD138, and Mum-1, while B cell markers CD20, CD10, PAX-5, and BCL-6 were rare. T cell marker CD3 was all negative. The median Ki-67 was 80% (30-90%), and EBER was positive (6/13, 46.2%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere is no standard treatment regimen for PBL. Traditional regimens used by various centers \u003csup\u003e[4]\u003c/sup\u003e include: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens, EPOCH (etoposide, vincristine, cyclophosphamide, doxorubicin, prednisone), hyper-CVAD-MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone, and high-dose methotrexate and cytarabine), CODOX-M/IVAC (cyclophosphamide, adriamycin, vincristine, methotrexate/isofosfamide, cytarabine, etoposide), etc. New regimens include: combination with bortezomib \u003csup\u003e[13]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, lenalidomide \u003csup\u003e[14]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, thalidomide \u003csup\u003e[15]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, PD-1 inhibitor \u0026nbsp;\u003csup\u003e[16]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, ASCT \u003csup\u003e[17]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e, CAR-T, etc. In this study, 13 patients all received standardized chemotherapy. Among them, 7 patients received the EPOCH regimen, 6 patients received CHOP or CHOP-like regimens, 5 patients received new drugs in the first line (3 cases combined with bortezomib, 1 case combined with lenalidomide, and 1 case combined with PD-1), and 3 cases combined with local radiotherapy. Except for 1 case who gave up treatment due to intolerance to toxic and side effects at an advanced age, and 1 case who refused to continue treatment due to personal reasons. After first-line treatment, 3 of the 11 patients had a response evaluation of CR, 6 cases had PR, 1 case had SD, and 1 case had PD. One case received a second-line regimen combined with autologous hematopoietic stem cell transplantation, and the efficacy reached CR from PR, but the disease relapsed quickly and the patient died. One case achieved PR after successively receiving the GDP regimen, DICE regimen, and DHAP regimen. One case achieved PR after receiving the MTX regimen combined with autologous hematopoietic stem cell transplantation. The best efficacy evaluation: 5 cases of CR, 6 cases of PR, 1 case of SD, and 1 case of NA. A total of 5 patients died, 2 died due to giving up treatment, and 3 died due to disease progression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to relevant literature statistics \u003csup\u003e[18]\u003c/sup\u003e\u003csup\u003e[19]\u003c/sup\u003e\u003csup\u003e[20]\u003c/sup\u003e, the median overall survival of PBL patients is 15 months, and the 3-year OS rate is 25%. Castillo JJ et al. \u003csup\u003e[21]\u003c/sup\u003e reported that the median OS of HIV-positive and negative PBL patients is 3 months and 4 months, respectively. In this study, the median OS time of PBL is 33.08 (11-79) months, which is significantly longer than previous reports, and there is no significant difference between the HIV-positive group and the negative group. This suggests that PBL first-line treatment combined with new drugs including bortezomib, lenalidomide, PD-1 inhibitor, RT, ASCT, etc. can effectively prolong survival.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, the data in this paper show that PBL is highly invasive, extranodal involvement is common, and it is prone to recurrence. A high IPI score is a poor prognostic indicator for PBL. After standardized anti-tumor treatment, the overall survival rate is significantly improved compared with previous reports, and it can overcome the adverse effect of HIV on prognosis. The treatment regimen is based on traditional regimens such as CHOP or EPOCH, combined with new drugs such as bortezomib, lenalidomide, or PD-1 inhibitor, combined with ASCT, which may improve the overall survival rate. However, this study is a retrospective analysis, and the number of cases is limited. Further multi-center, prospective studies are needed for further exploration.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX1150), Fundamental Research Funds for the Central Universities (2022CDJYGRH-001) and Chongqing Professional Talents Plan (cstc2022ycjh-bgzxm0048).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.P.L.,,Y.L. were responsible for the conception and design of the study. D.H.H.,, Y.X,, Q.Y.L.,, Y.Y.N, were responsible for participant recruitment. Q.Q., Y.X., J.Y.L., were responsible for participant follow-up and clinical data acquisition. J.L.,Z.L.Y., C.L.H., L.X.X., T.T.L., were responsible for Sample testing and data acquisition. B.L.G., were responsible for manuscript writing and revision. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDECLARATION OF COMPETING INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAVAILABILITY OF DATA AND MATERIALS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL AND CONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the local research ethics committee of the Chongqing University Cancer Hospital.\u003c/p\u003e\n\u003cp\u003eThe requirement for informed consent was waived by the Institutional Review Board because of the study\u0026rsquo;s retrospective nature.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n\u003cli\u003eRamirez-Gamero A, Mart\u0026iacute;nez-Cordero H, Beltr\u0026aacute;n BE, et al. Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management. Am J Hematol. 2024 Aug;99(8):1586-1594. doi: 10.1002/ajh.27376. Epub 2024 May 20. PMID: 38767403.\u003c/li\u003e\n\u003cli\u003eCastillo JJ, Winer ES, Stachurski D, et al. Prognostic factors in chemotherapy-treated patients with HIV-associated Plasmablastic lymphoma. Oncologist. 2010;15(3):293-9. doi: 10.1634/theoncologist.2009-0304. Epub 2010 Feb 18. PMID: 20167839; PMCID: PMC3227958.\u003c/li\u003e\n\u003cli\u003eNCCN guidelines version 1.2024. HIV-related B-cell lymphomas.Accessed February 20, 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. Blood. 2024 Jan 11;143(2):152-165. doi: 10.1182/blood.2023021348. PMID: 37832030.\u003c/li\u003e\n\u003cli\u003eCheson BD , Fisher RI , Barrington SF ,et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification[J]. J Clin Oncol, 2014,32(27):3059-3068. DOI: 10.1200/JCO.2013.54.8800\u0026ensp;.\u003c/li\u003e\n\u003cli\u003eCheson BD , Pfistner B , Juweid ME ,et al. Revised response criteria for malignant lymphoma[J]. J Clin Oncol, 2007,25(5):579-586. DOI: 10.1200/JCO.2006.09.2403\u0026ensp;.\u003c/li\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. Blood. 1997 Feb 15;89(4):1413-20. PMID: 9028965.\u003c/li\u003e\n\u003cli\u003eQunaj L, Castillo JJ, Olszewski AJ, et al. Survival of patients with CD20-negative variants of large B-cell lymphoma: an analysis of the National Cancer Data Base. Leuk Lymphoma. 2018 Jun;59(6):1375-1383. doi: 10.1080/10428194.2017.1387912. Epub 2017 Oct 11. PMID: 29019447.\u003c/li\u003e\n\u003cli\u003eRafaniello Raviele P, Pruneri G, et al. Plasmablastic lymphoma: a review. Oral Dis. 2009 Jan;15(1):38-45. doi: 10.1111/j.1601-0825.2008.01493.x. Epub 2008 Oct 7. PMID: 18939960.\u003c/li\u003e\n\u003cli\u003eCarbone A, Gloghini A, Larocca LM, et al. Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. Blood. 2001 Feb 1;97(3):744-51. doi: 10.1182/blood.v97.3.744. PMID: 11157493.\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. Blood. 2024 Jan 11;143(2):152-165. doi: 10.1182/blood.2023021348. PMID: 37832030.\u003c/li\u003e\n\u003cli\u003eCastillo JJ, Bibas M, Miranda RN, et al. The biology and treatment of plasmablastic lymphoma. Blood. 2015 Apr 9;125(15):2323-30. doi: 10.1182/blood-2014-10-567479. Epub 2015 Jan 30. PMID: 25636338.\u003c/li\u003e\n\u003cli\u003eGuerrero-Garcia TA , Mogollon RJ , Castillo JJ . Bortezomib in plasmablastic lymphoma: A glimpse of hope for a hard-to-treat disease[J]. Leuk Res, 2017,62:12-16. doi: 10.1016/j.leukres.2017.09.020\u0026ensp;.\u003c/li\u003e\n\u003cli\u003eAndo K , Imaizumi Y , Kobayashi Y ,et al. Bortezomib- and Lenalidomide-Based Treatment of Refractory Plasmablastic Lymphoma[J]. Oncol Res Treat, 2020,43（3）:112-116. doi: 10.1159/000504608\u0026ensp;.\u003c/li\u003e\n\u003cli\u003eBroccoli A , Nanni L , Stefoni V ,et al. A patient with plasmablastic lymphoma achieving long-term complete remission after thalidomide-dexamethasone induction and double autologous stem cell transplantation: a case report[J]. BMC Cancer, 2018,18（1）:645. doi: 10.1186/s12885-018-4561-9\u003c/li\u003e\n\u003cli\u003eDamlaj M , Alzayed M , Alahmari B ,et al. Therapeutic Potential of Checkpoint Inhibitors in Refractory Plasmablastic Lymphoma[J]. Clin Lymphoma Myeloma Leuk, 2019,19（10）:e559-e563. doi: 10.1016/j.clml.2019.06.008\u0026ensp;.\u003c/li\u003e\n\u003cli\u003eBroccoli A , Nanni L , Stefoni V ,et al. A patient with plasmablastic lymphoma achieving long-term complete remission after thalidomide-dexamethasone induction and double autologous stem cell transplantation: a case report[J]. BMC Cancer, 2018,18（1）:645. doi: 10.1186/s12885-018-4561-9\u0026ensp;.\u003c/li\u003e\n\u003cli\u003eCastillo J, Pantanowitz L, Dezube BJ, et al. HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases. Am J Hematol. 2008 Oct;83(10):804-9. doi: 10.1002/ajh.21250. PMID: 18756521.\u003c/li\u003e\n\u003cli\u003eFedele PL, Gregory GP, Gilbertson M, et al. Infusional dose-adjusted epoch plus bortezomib for the treatment of plasmablastic lymphoma. Ann Hematol. 2016 Mar;95(4):667-8. doi: 10.1007/s00277-016-2601-6. Epub 2016 Jan 23. PMID: 26801792.\u003c/li\u003e\n\u003cli\u003eBibas M, Grisetti S, Alba L, et al. Patient with HIV-associated plasmablastic lymphoma responding to bortezomib alone and in combination with dexamethasone, gemcitabine, oxaliplatin, cytarabine, and pegfilgrastim chemotherapy and lenalidomide alone. J Clin Oncol. 2010 Dec 1;28(34):e704-8. doi: 10.1200/JCO.2010.30.0038. Epub 2010 Sep 7. PMID: 20823416.\u003c/li\u003e\n\u003cli\u003eCastillo JJ , Winer ES , Stachurski D ,et al. Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma[J]. Leuk Lymphoma, 2010,51（11）:2047-2053. doi: 10.3109/10428194.2010.516040\u0026ensp;.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"analysis, plasmablastic lymphoma","lastPublishedDoi":"10.21203/rs.3.rs-5917684/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5917684/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e To explore the clinical characteristics, treatment, and prognosis of patients with newly diagnosed plasmablastic lymphoma (PBL).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e The clinical data of 13 newly diagnosed PBL patients admitted to Chongqing University Cancer Hospital from January 2013 to June 2024 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier survival curve and Log-rank test. Univariate and multivariate Cox regression model analyses were used for analyzing prognostic factors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e ①The number of male and female cases was 10:3. The median age was 52.15 (26-78) years old. Six cases (46.1%) had extranodal organ involvement as the initial symptom, including 3 cases (23.1%) of oral and maxillofacial region. There were 7 cases (53.9%) in Ann-Arbor stage Ⅰ~Ⅱ and 6 cases (46.1%) in stage Ⅳ. Six cases (46.1%) had B symptoms. Two cases (15.3%) had an IPI score ≥3. Nine cases (69.2%) had elevated peripheral blood EB-DNA detection. One case had bone marrow invasion (7.7%), and one case had central nervous system invasion. ②All patients expressed CD38, CD138, and MUM-1. B-cell markers such as PAX-5 and Bcl-6 were occasionally seen. Six cases (46.2%) had positive EBER detection. ③All 13 patients received chemotherapy, and 3 cases received combined radiotherapy. The median follow-up was 48.31 (16-141) months. The median OS was 33.08 (11-79) months, and the median PFS was 25.62 (2-79) months. ④Seven cases received the EPOCH regimen, 6 cases received the CHOP or CHOP-like regimen. Five cases received new drugs in the first-line treatment (3 cases combined with bortezomib, 1 case combined with lenalidomide, and 1 case combined with a PD-1 inhibitor). Three cases received combined local radiotherapy. After first-line treatment, 5 cases had a CR evaluation, 6 cases had a PR evaluation, 1 case had SD, and 1 case had NA. ⑤The best efficacy evaluation: 5 cases had CR, 7 cases had PR, and 1 case had NA. The combination of new drugs and autologous stem cell transplantation (ASCT) in the first-line treatment had obvious benefits, but the use of new drugs such as Lenalidomide and Selinexor in the third-line and above had poor effects. ⑥Kaplan-Meier analysis showed that the overall survival of PBL was significantly related to IPI score 3-5, B symptoms, and male gender (P\u0026lt;0.05). According to univariate COX regression analysis, for newly diagnosed PBL, anemia (≤120g/L) and IPI score 3-5 were factors for poor prognosis of PFS. IPI score 3-5 was a factor for poor prognosis of OS. Combined HIV infection had no significant impact on prognosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e For PBL treated through standardized treatment, the impact of HIV infection on prognosis can be overcome. At initial diagnosis, anemia (≤120g/L) and IPI score 3-5 are factors for poor prognosis of PFS in PBL. IPI score 3-5 is a factor for poor prognosis of OS. The first-line treatment choice of combining new drugs (Bortezomib, Lenalidomide, PD-1 inhibitor) and ASCT is expected to improve the prognosis of PBL.\u003c/p\u003e","manuscriptTitle":"Clinical characteristics and prognosis analysis of 13 cases of newly diagnosed plasmablastic lymphoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-13 09:58:37","doi":"10.21203/rs.3.rs-5917684/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"01fa39b5-a1de-4cba-80c9-aa63ce66c107","owner":[],"postedDate":"February 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-19T07:38:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-13 09:58:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5917684","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5917684","identity":"rs-5917684","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}