Clinical features and prognostic outcomes of systemic anaplastic large cell lymphoma in a Chinese multicenter study

Clinical features and prognostic outcomes of systemic anaplastic large cell lymphoma in a Chinese multicenter 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 Research Article Clinical features and prognostic outcomes of systemic anaplastic large cell lymphoma in a Chinese multicenter study Sheng-Sheng Zhou#, Mei Zhou#, Hai-Yan Yang, Man Wang, Zhong-Qiong Wei, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7163556/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective The prevalence of systemic anaplastic large cell lymphoma (sALCL) is low and remains under-investigated. This study aimed to investigate the clinical features, treatment outcomes, and prognostic factors of sALCL. Methods A retrospective analysis of 143 sALCL patients treated at 14 centers from 2010 to 2022 was conducted. Results The median age was 44 years, with a male predominance. Most patients were diagnosed at an advanced stage, and extranodal involvement, particularly in the bone, was observed in 51.0% of cases. Most patients exhibited elevated LDH, β2-MG, CD30 positivity, and high Ki-67 expression. ALK-positivity was found in 55.9% of patients, who were significantly younger than ALK-negative patients ( p < 0.001). First-line chemotherapy achieved a complete response (CR) rate of 66.7% and an overall response rate (ORR) of 78.5%. CHOPE was more effective than CHOP. Failure to achieve complete response, age ≥ 60 years, bone marrow involvement, and elevated β2-MG were identified as independent prognostic factors for survival. Conclusion This study highlights the unique distinct clinical and molecular features of sALCL in the real world of China and suggests that ALK expression and treatment regimen significantly influence outcomes, providing new data for clinical practice. systemic anaplastic large cell lymphoma clinical characteristics prognostic analysis multi-center study Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Anaplastic large cell lymphoma (ALCL) is a highly aggressive and heterogeneous subtype of peripheral T-cell lymphoma, comprising about 2% of non-Hodgkin's lymphomas ( 1 ) . Strong expression of anaplastic lymphoma kinase (ALK) and CD30 defines ALK-positive ALCL (ALK + ALCL) ( 2 ) . ALK, located on chromosome 2p23.2-p23.1, undergoes translocation with chromosome 5, forming the NPM::ALK fusion tyrosine kinase, which activates pathways driving cancer pathogenesis. For example, CD30 in NPM::ALK -expressing cells triggers the NF-κB pathway and induces anti-apoptotic effects via p38/MAPK, promoting ALCL ( 3 , 4 ) . However, subsequent studies have revealed that ALK expression is not the sole factor driving ALCL pathogenesis. Nonetheless, ALK expression serves as a defining characteristic of this group of disorders. Consequently, in 2016, the World Health Organization classified ALCL into ALK-positive (ALK + ALCL) and ALK-negative (ALK- ALCL) subtypes ( 5 ) , each with distinct clinical features, diagnostic markers, and prognoses. Several studies have found that ALK + ALCL is more common in individuals under 50 years of age. Its typical clinical manifestations include weight loss, fever, weakness, malaise, and night sweats. Additionally, it is often associated with peripheral or abdominal lymph node enlargement, extra-nodal infiltration, and bone marrow involvement ( 6 – 8 ) . Despite the advanced stage at diagnosis and diverse symptoms, many patients achieve remission with first-line treatments like CHOP, resulting in a 5-year overall survival rate of 70–90% (8–10) . In contrast, ALK- ALCL predominantly affects individuals aged 50 years or older. These patients less frequently present with lymph node enlargement or extra-nodal infiltration, and first-line treatments such as CHOP are generally ineffective. Their prognosis is poorer compared to ALK + ALCL, with a 5-year overall survival rate of only 30–49% (8, 11–13) . Different ALCL subtypes exhibit distinct therapeutic outcomes and prognoses, making early diagnosis crucial. Molecular markers play a critical role in diagnosis and subtype classification of ALCL. Laurence et al. suggested that BCL6, CEBPB, and SERPINA1 are potential markers for ALK + ALCL, while CCR7 and CNTFR are indicative of ALK- ALCL ( 14 ) . Filippa et al. also proposed molecular markers; however, their application in clinical practice remains limited ( 7 , 15 ) . In the 5th edition of the WHO Classification of Hematolymphoid Tumours, ALCL is subdivided into systemic ALK-positive ALCL (ALK + sALCL), systemic ALK-negative ALCL (ALK- sALCL), primary cutaneous ALCL, and breast implant-associated ALCL ( 2 ) . While these subtypes share similar cytomorphologic and phenotypic features, they differ in genomic backgrounds and clinical courses ( 16 ) . The prevalence of sALCL is low and remains under-investigated. Previous studies on sALCL were mostly based on small sample sizes, with significant variability between ALK + sALCL and ALK- sALCL, necessitating further research to enhance understanding of the disease. This study retrospectively examined 143 sALCL patients across 14 research centers in China to summarize their clinical features, immunohistochemical characteristics, therapeutic efficacy, and prognosis, providing insights into its clinical diagnosis, prognostic assessment, and treatment strategies. 2. Information and methods 2.1 Case information This study collected data from 143 patients diagnosed with systemic anaplastic large-cell lymphoma (sALCL) between April 2010 and April 2022 from 14 study centers. The specific hospital names and the number of patients were shown in Table 1 . All patients were definitively diagnosed through pathological analysis, and their diagnosis conformed to the 2016 WHO classification criteria. Baseline data, retrieved from electronic medical records, included demographics (age, gender), comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, pathology and immunohistochemistry results, blood biochemistry, bone marrow aspiration, and imaging data such as CT/PET-CT, which were analyzed to determine the extent of lymph node involvement or extranodal lesions, the Ann Arbor stage, and the International Prognostic Index (IPI) for lymphoma. Based on the IPI score, patients were categorized into four risk groups: low risk (0–1), low-intermediate risk (2), intermediate-high risk (3), and high risk (4–5). Table 1 14 study centers and number of patients. Hospital Number of patients Hospital Number of patients the People's Hospital of Hainan Province 42 the Union Hospital of Fujian Medical University 16 the People's Hospital of Guangdong Province 41 the Nanfang Hospital of Nanfang Medical University 8 the Shenzhen Municipal People's Hospital 7 the First Affiliated Hospital of Kunming Medical University 7 the Shenzhen Hospital of Peking University 5 Kunhua Hospital of the First People's Hospital of Yunnan Province 5 Sun Yat-sen Memorial Hospital of Sun Yat-sen University 4 Fujian Provincial Hospital 2 the First Affiliated Hospital of Fujian Medical University 2 the Affiliated Hospital of Guangdong Medical University 2 the First Affiliated Hospital of Guangxi Medical University 1 Zhuhai People's Hospital 1 2.2 Treatment plan Among the 143 patients, 135 received first-line chemotherapy, whereas 7 were treated with alternative regimens, including radiotherapy and steroid hormone therapy. Treatment data were unavailable for one patient. Among the patients who received first-line chemotherapy, three were excluded for not meeting the group treatment criteria. The remaining 132 patients underwent the following regimens: 61 received CHOP, 49 CHOPE, 9 BV + CHP, 5 CDOP, 5 P-GemOx, and one each received BFM-90, CVP, or Hyper-CVAD. Eight patients underwent intensive autologous hematopoietic stem cell transplantation (AHSCT) following remission from first-line treatment, and six achieved remission without relapse. Second-line chemotherapy was provided to patients who did not achieve remission with first-line treatment or experienced relapse. 2.3 Evaluation of efficacy Recent efficacy was assessed based on the International Lymphoma Efficacy Evaluation Criteria ( 16 ) and classified as Complete Remission (CR), Partial Remission (PR), Stable Disease (SD), or Progressive Disease (PD). The complete response rate (CR rate) was calculated as CR / (CR + PR + SD + PD). The Overall Response Rate (ORR) was calculated as (CR + PR) / (CR + PR + SD + PD). 2.4 Survival follow-up In this study, patient survival data were primarily obtained from the electronic medical record system of the study center and through telephone follow-ups, with a cut-off date of December 2022. The primary outcomes were progression-free survival (PFS) and overall survival (OS). OS was defined as the time (in months) from the date of diagnosis to the date of death or last follow-up. PFS was defined as the time (in months) from the date of diagnosis to disease progression/recurrence, death, or last follow-up. 2.5 Statistical analysis All statistical analyses were conducted using SPSS 23.0 and R 4.4.1. The chi-square test or Fisher's exact test was applied for comparing categorical variables between groups. The Kaplan-Meier method was used to estimate median survival time and generate survival curves, while the log-rank test was applied to compare survival curves. Univariate and multivariate analyses were performed using the Cox proportional-hazards model. A p-value < 0.05 was considered statistically significant. 3. Results 3.1 Clinical information The study cohort consisted of 143 patients, including 138 newly treated cases and 5 relapsed cases. The male-to-female ratio was 2.04:1. The median age of onset was 44 years (range: 13–87). Among the 73 patients with extranodal involvement, the most commonly affected sites were the bone, lung, bone marrow, and skin. Table 2 summarizes the baseline characteristics of the 143 patients. Patients were categorized into two groups: ALK-positive and ALK-negative. The median age was 33 years (range: 13–85) in the ALK-positive group, with a mean age of 36 ± 17 years, compared to a median age of 53 years (range: 15–87) and mean age of 52 ± 16 years in the ALK-negative group. ALK-negative patients were significantly older than ALK-positive patients ( p < 0.001). But no statistically significant differences were observed between the two groups in terms of gender, comorbidities, extranodal involvement, bone marrow findings, Ann Arbor stage, ECOG score, or IPI score ( p > 0.05, Table 3 ). Table 2 Patient clinical characteristics. Clinical characteristics Number of cases Sex male 96 (67.1%) female 47 (32.9%) Age >=60 years 30 (21.0%) = 2 27 (18.9%) ECOG > = 2 27 (18.9%) Ann Arbor Ⅰ-Ⅱ stage 37 (25.9%) Ⅲ-Ⅳ stage 102 (71.3%) IPI scores low-risk group 45 (31.5%) low-intermediate-risk group 48 (33.6%) intermediate-high-risk group 37 (25.9%) high-risk group 9 (6.3%) Hemophagocytic Syndrome ALK positive negative 4 80 (55.9%) 63 (44.1%) 3.2 Blood biochemistry Among the 143 patients, lactate dehydrogenase (LDH) levels were available for 142 patients; LDH was elevated in 123 patients (86.6%), including 6 patients with LDH > 500 U/L. β2-microglobulin (β2-MG) levels were unavailable for 11 patients, but were elevated in 114 patients (86.4%). There was no statistically significant difference in the rates of elevated LDH and β2-MG between the ALK-positive and ALK-negative groups ( p > 0.05). Table 3 presents the differences in clinical characteristics and blood biochemistry between the two groups. Table 3 Clinical characteristics and blood biochemistry of ALK-positive and ALK-negative sALCL patients. clinical characteristics/blood biochemistry ALK + sALCL ALK- sALCL χ2 p Median age 33(13–85) 53(15–87) = 2 16 11 0.199 0.655 IPI = 3–5 25 21 0.289 0.591 Elevated LDH 72 51 3.138 0.076 Elevated β2-MG 66 48 2.272 0.132 Note: * indicates a statistically significant difference between the two groups. 3.3 Immunohistochemical characteristics The majority of patients (98.6%) were CD30-positive, except for 4 patients who were not tested. All cases tested for Ki-67 demonstrated high expression, with a median value of 80.0%. Most cases tested for TdT and EBER yielded negative results. The ALK-positive group exhibited significantly higher positivity rates for TIA-1 ( p = 0.018, χ 2 = 5.568) and granzyme B (p = 0.018, χ 2 = 5.622) compared to the ALK-negative group. The proportions of immunohistochemical markers in the ALK-positive and ALK-negative groups are detailed in Table 4 . Table 4 Immunohistochemical characterization table. Immunohistochemistry Group ALK-positive group ALK-negative group Total cases CD30 positive 78(56.1%) 59(42.4%) 137(98.6%) negative 1(0.7%) 1(0.7%) 2(1.4%) Ki-67 positive 69(56.1%) 54(43.9%) 123(100%) negative 0(0%) 0(0%) 0(0%) TdT positive 2(8.7%) 1(4.3%) 3(13.0%) negative 13(56.5%) 7(30.4%) 20(87.0%) TIA-1 positive 32(51.6%) 19(30.6%) 51(82.3%) negative 2(3.2%) 9(14.5%) 11(17.7%) Granzyme B positive 25(54.3%) 13(28.3%) 38(82.6%) negative 1(2.2%) 7(15.2%) 8(17.4%) EBER positive 2(2.0%) 4(4.0%) 6(5.9%) negative 54(53.5%) 41(40.6%) 95(94.1%) 3.4 Efficacy evaluation Among the 135 patients who received first-line chemotherapy, 90 patients achieved CR, 16 patients achieved PR, 7 patients were evaluated as having SD, and 22 patients were evaluated as having PD. The CR rate was 66.7%, and the ORR was 78.5%. The CR rate in the ALK-positive group was 71.0%, with an ORR of 80.3%, while the CR rate in the ALK-negative group was 61.0%, with an ORR of 76.3%. There was no statistically significant difference between the two groups. In this study, 61 patients received CHOP, with a CR rate of 54.0% and an ORR of 67.2%; 49 patients received CHOPE, with a CR rate of 81.6% and an ORR of 89.8%; and 9 patients received BV + CHP, with a CR rate of 77.7% and an ORR of 88.9%. The chi-square test results showed that the CR rate (χ2 = 9.726, p = 0.006) and ORR (χ2 = 8.474, p = 0.012) of the three chemotherapy regimens were significantly different, with a significant difference between CHOP and CHOPE, the latter being significantly superior to the former. However, there were no statistically significant differences between CHOP and BV + CHP, and between CHOPE and BV + CHP. 3.5 Prognostic analysis Of the 143 patients with sALCL, 134 patients had complete follow-up data, including 32 deaths and 102 survivors by the end of follow-up, while 9 patients were lost to follow-up, resulting in a follow-up rate of 93.7%. The median follow-up time for this study was 31 months (range: 0.1–99.2 months), and the median OS and the median PFS were not reached. In the ALK-negative group, the median OS was 71.9 months, while the median PFS was not reached. In the ALK-positive group, both the median OS and median PFS were not reached. Log-rank analysis revealed significant differences in the OS and PFS survival curves between the ALK-negative and ALK-positive groups, indicating that ALK-negativity was a risk factor for both OS and PFS ( p < = 0.001, Fig. 1 ). When analyzing only sub-youth patients (aged < = 44 years), the ALK-negative group exhibited worse prognoses than the ALK-positive group, but the difference was not statistically significant (Fig. 2 ). Cox univariate analysis identified ALK-negativity, age > = 60 years, elevated β2-MG, and failure to achieve CR with first-line treatment as risk factors for PFS. For OS, bone marrow infiltration is a risk factor rather than elevated β2-MG (Fig. 3 ). Multivariate analysis revealed that elevated β2-MG and failure to achieve CR with first-line treatment were independent poor prognostic factors for PFS, while for OS, additional independent factors included age > = 60 years and bone marrow involvement, but not elevated β2-MG (Fig. 4 ). 4. Discussion Systemic anaplastic large cell lymphoma (sALCL) is a malignant lymphoma defined by its pronounced aggressiveness and significant heterogeneity. It consists of distinctive large pleomorphic lymphoid cells with abundant cytoplasm and nuclei shaped like horseshoes. Based on ALK expression, sALCL is categorized into ALK-positive and ALK-negative subtypes, which differ in clinical symptoms, treatment responses, and prognoses, with their diagnostic markers yet to be fully established ( 7 , 8 , 17 , 18 ) . Consequently, distinguishing between the two subtypes based solely on ALK expression is challenging, and relying on ALK expression alone to evaluate therapeutic efficacy and prognosis is imprecise. Thus, further insights into the clinical characteristics, therapeutic outcomes, prognostic factors, and molecular features of sALCL are essential to optimize diagnostic and therapeutic strategies. In terms of clinical features, this study found that male patients were predominant, with a median onset age of 44 years. The majority of patients were in advanced stages (Ann Arbor stage III-IV), representing 71.3% of cases at the time of consultation. Approximately 25.2% of patients had comorbidities, with extranodal involvement observed in 51.0% at initial treatment, and > = 2 extranodal sites involved in 37.0% of cases. The most frequently involved sites were bone, lung, bone marrow, and skin. These findings are broadly consistent with prior studies on sALCL ( 18 , 19 ) . Multiple studies have demonstrated a higher prevalence of ALK + sALCL compared to ALK- sALCL ( 18 , 20 ) . Age is among the most significant distinguishing factors between the two subtypes. ALK + sALCL primarily affects younger individuals, whereas most patients with ALK- sALCL are aged 40 to 65. Our study observed a slightly higher number of patients with ALK + sALCL compared to ALK- sALCL. Furthermore, patients with ALK + sALCL were significantly younger than those with ALK- sALCL, with a statistically significant difference between the two groups ( p < 0.001), consistent with prior findings. It has been reported that ALK + ALCL patients are more likely to exhibit bone marrow involvement ( 21 ) ; however, this was not statistically significant in our study. Moreover, no statistically significant differences were observed between the two groups in terms of gender, comorbidities, incidence of extranodal involvement, Ann Arbor staging, ECOG, or IPI scores, findings that align with previous studies. Furthermore, our study revealed that β2-MG, a biochemical marker indicative of tumor burden, was more frequently elevated in the ALK + sALCL group. Although consistent with trends observed in a retrospective study of sALCL ( 22 ) , the differences in our findings were not statistically significant, warranting further investigation. Similarly, our findings regarding the proportion of elevated LDH, which showed no statistically significant differences between the groups, were consistent with previous studies. All ALCLs share common morphological, immunophenotypic, and gene expression features; however, ALCL represents a heterogeneous group of clinicopathologic entities rather than a single disease ( 23 ) . Immunohistochemical analysis plays a critical role in the accurate diagnosis of sALCL. In this study, the vast majority of patients were found to be CD30 positive with high Ki-67 expression. Additionally, most patients were positive for TIA-1 and granzyme B, while the majority were negative for TdT and EBER in tumor cells, suggesting that the development of ALCL is not associated with Epstein-Barr virus (EBV) infection. These findings are largely consistent with previous studies ( 11 , 19 , 24 ) . A comparison between the ALK + sALCL group and the ALK- sALCL group revealed significantly higher positivity rates for TIA-1 and granzyme B in the former. This finding aligns with conclusions from multiple domestic and international studies. Furthermore, cytotoxic molecules such as TIA-1 and granzyme B have been utilized as markers to differentiate ALK + sALCL from other lymphomas ( 25 ) . Anthracycline-containing multidrug regimens remain the gold standard for treating sALCL. The National Comprehensive Cancer Network (NCCN) guidelines recommend treatment regimens such as BV combined with CHP, CHOP, CHOEP, dose-adjusted EPOCH, and autologous stem cell transplantation as first-line consolidation therapies. Numerous studies, including ours, have demonstrated that CHOPE significantly improves event-free survival in ALCL patients ( 26 , 27 ) . Our study reported a CR rate of 54.0% and an ORR of 67.2% with CHOP, a CR rate of 81.6% and an ORR of 89.8% with CHOPE, and a CR rate of 77.7% and an ORR of 88.9% with BV + CHP. Among these regimens, CHOPE demonstrated significantly greater efficacy compared to CHOP. However, due to increased toxicity, CHOPE is primarily reserved for younger patients with ALK + sALCL. BV + CHP exhibited notable therapeutic effects and outperformed CHOP in our study, consistent with the ECHELON-2 study ( 28 ) ; however, the results were not statistically significant, likely due to sample size limitations. Hematopoietic stem cell transplantation is widely recommended as a first-line consolidation therapy for patients with ALK- sALCL and high-risk ALK + sALCL ( 29 ) . In our study, eight patients underwent autologous hematopoietic stem cell transplantation (AHSCT) after achieving remission with first-line therapy, and six remained relapse-free, demonstrating satisfactory outcomes. Given the relatively poor efficacy in treating ALK- sALCL, some studies have attempted intensified chemotherapy regimens or novel drug combinations with CHOP, such as hyper-CVAD, but these approaches have shown limited success ( 30 ) . Nevertheless, combining novel agents, such as ALK inhibitors and CD30 monoclonal antibodies, with CHOP regimens represents an emerging trend in ALCL treatment ( 31 ) . Thus, the integration of novel drugs with CHOP regimens is expected to become a focal point in future ALCL research. Numerous studies have investigated the prognostic factors influencing sALCL. Among these, the relationship between ALK expression and the prognosis of sALCL patients has been extensively studied, but its prognostic value remains controversial. Overall, ALK + sALCL patients are generally believed to have a better prognosis than those with ALK- sALCL. One study reported a 5-year survival rate of 70–86% for ALK + sALCL patients, compared to only 30–49% for ALK- sALCL patients ( 11 ) . Furthermore, the 5-year overall survival (OS) of treated ALK + sALCL patients was 70–90%, compared to 40–60% for ALK- sALCL patients ( 32 ) . However, it has been suggested that these differences may be attributed to variations in age of onset and staging. When controlling for factors such as age and stage, no significant prognostic differences were observed between ALK + and ALK- sALCL patients ( 8 ) . Nonetheless, a subgroup survival analysis of sALCL patients under 40 years revealed that even within this age group, the difference in OS between the two groups remained statistically significant ( 33 ) . In our study, ALK-negativity emerged as a significant risk factor for both OS and PFS across all age groups ( p < 0.001). However, in patients younger than young adults, ALK-negativity still exhibited a trend toward poorer prognosis, though the difference was not statistically significant. ALK expression also was excluded from the multivariate analysis. Additionally, failure to achieve CR with first-line therapy was identified as independent risk factor for OS and PFS. Age > = 60 years and bone marrow involvement were an independent risk factors for OS, while elevated β2-MG was an independent risk factor for PFS. Among these, bone marrow involvement as an adverse prognostic factor for OS has been confirmed in a retrospective study and several reviews ( 34 ) . This study collected data from 143 patients with sALCL through a multicenter collaboration, enabling a more representative retrospective analysis. In summary, this study represents a multicenter effort with one of the largest sample sizes in this field. Our findings indicate that sALCL predominantly affects males and is characterized by extranodal involvement, serological abnormalities, and specific immunohistochemical features. Significant differences were observed between ALK-negative and ALK-positive patients in certain clinical features. CHOP(E) remains the most widely used first-line treatment option, demonstrating favorable outcomes. Failure to achieve CR with first-line therapy was identified as an independent adverse prognostic factor for PFS and OS. Additionally, age ≥ 60 years and bone marrow involvement independently impacted OS, while elevated β2-MG independently impacted PFS. The prognostic impact of ALK expression requires further investigation, accounting for potential confounding factors. Although this study included a large sample size, most cases originated from southeastern China, and inherent limitations of retrospective analysis necessitate further prospective studies. Declarations Competing interests the authors have no competing interests. Patient consent statement The informed consent was waived considering the retrospective nature of the study. Ethics statement The study was approved by the institutional review board of First Affiliated Hospital of Guangxi Medical University (Y2025361) and each participating center, waiving the requirement for patient consent. Clinical trial number Not applicable. Funding During the course of this research, we did not receive any form of financial support. All required funding was provided by the researchers personally or by their affiliated institutions. Author Contribution R.H., J.M., S.Z. and M.Z. conceived and designed the study. S.Z., J.L., H.Y., M.W. and G.C. collected data. S.Z., M.Z, Z.W., K.C., D.Q. and Z.P. did statistical analysis and clinical interpretation. M.Z. and Z.W. drafted initial manuscript. All the authors critically reviewed the manuscript. All the authors read and approved the final report. Acknowledgement We thank all patients involved in this study at 14 medical centers. Data availability All data supporting the findings of this study are available within the paper. References A clinical evaluation of the International Lymphoma Study Group. classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997;89(11):3909–18. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720–48. 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Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010;116(18):3418–25. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin oncology: official J Am Soc Clin Oncol. 2012;30(18):2190–6. Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126(1):17–25. Wei C, Zhao DQ, Zhang Y, Wang W, Zhang W, Zhou DB. Clinical characteristics and prognostic analysis of 48 cases of primary systemic anaplastic large cell lymphoma. J Clin Hematol. 2022;35(01):52–7. Doghri R, HadjKacem LB, Houcine Y, Charfi L, Driss M, Kacem K, et al. Prognostic factors of ALK-negative anaplastic large-cell lymphoma: a single-institution experience. Ann Hematol. 2018;97(4):725–6. Additional Declarations No competing interests reported. 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7163556","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":504795027,"identity":"da9a7970-f9d5-4d31-813d-b371524ea4ad","order_by":0,"name":"Sheng-Sheng Zhou#","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Sheng-Sheng","middleName":"","lastName":"Zhou#","suffix":""},{"id":504795031,"identity":"d132eec9-8a9b-4fc2-bbd2-ad915ff86bc6","order_by":1,"name":"Mei Zhou#","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Zhou#","suffix":""},{"id":504795035,"identity":"15d2253f-d1ab-418a-85a4-ea2f4f547ac1","order_by":2,"name":"Hai-Yan Yang","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Hai-Yan","middleName":"","lastName":"Yang","suffix":""},{"id":504795038,"identity":"c520578a-99d2-49ed-a088-708630de799b","order_by":3,"name":"Man Wang","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Man","middleName":"","lastName":"Wang","suffix":""},{"id":504795040,"identity":"61fac6e0-e437-48f0-8f81-0c0d8115cd6c","order_by":4,"name":"Zhong-Qiong Wei","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Zhong-Qiong","middleName":"","lastName":"Wei","suffix":""},{"id":504795045,"identity":"7f55cea2-758a-43d3-8d34-46572472b469","order_by":5,"name":"Kai-Teng Cai","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Kai-Teng","middleName":"","lastName":"Cai","suffix":""},{"id":504795047,"identity":"b1edc156-597e-4a90-a740-01a2d94d4d0f","order_by":6,"name":"Di-Yuan Qin","email":"","orcid":"","institution":"Guangxi University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Di-Yuan","middleName":"","lastName":"Qin","suffix":""},{"id":504795049,"identity":"461158ea-65ab-48e7-a7f5-f453b0225be3","order_by":7,"name":"Jian-Di Li","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Jian-Di","middleName":"","lastName":"Li","suffix":""},{"id":504795050,"identity":"e881ad13-c333-4bc8-b37d-3a941a4b26e2","order_by":8,"name":"Gang Chen","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Gang","middleName":"","lastName":"Chen","suffix":""},{"id":504795051,"identity":"c05e5427-8ef0-495a-b090-55e80fab8cbf","order_by":9,"name":"Zhi-Gang Peng","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Zhi-Gang","middleName":"","lastName":"Peng","suffix":""},{"id":504795053,"identity":"58158fc4-eb5a-4964-90dd-590668360a83","order_by":10,"name":"Jie Ma","email":"","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Ma","suffix":""},{"id":504795054,"identity":"8472a029-9aa9-4874-b4f9-925c180b218f","order_by":11,"name":"Rong-Quan He","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYBADOTb29gOkaTHm4zmTQJqWxHkSDgbEKZWfdoD5NW/O4fQ2CYYEhh8V2whrYZydwGY5c9vh3DbpxgOMPWduE9bCLJ3AZvARpEXmQAIzYxsRWthAWhK3HU5nk0gwIE4Lj3QC8wOgLQnEa5EA2sI4c1u6YRswkA8S5Rf52QnMn3m3WcvLt7cffPCjgggtDAz83yRgzAPEqAcB5g/EqhwFo2AUjIIRCgB9Pje6H9lo5AAAAABJRU5ErkJggg==","orcid":"","institution":"First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region","correspondingAuthor":true,"prefix":"","firstName":"Rong-Quan","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2025-07-19 09:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7163556/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7163556/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89976221,"identity":"ac1efa4b-e18d-4d93-9482-d4601bab611e","added_by":"auto","created_at":"2025-08-27 06:00:38","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":161628,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of ALK expression on OS and PFS.\u003c/p\u003e\n\u003cp\u003eOS curve on the left and PFS curve on the right.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7163556/v1/16a8fa28d8c600b68af55849.jpeg"},{"id":89976224,"identity":"11ab2be8-7c08-4700-bdf9-dfaf9e230a22","added_by":"auto","created_at":"2025-08-27 06:00:38","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":146060,"visible":true,"origin":"","legend":"\u003cp\u003eEffect of ALK expression on OS and PFS in sub-youth patients.\u003c/p\u003e\n\u003cp\u003eOS curve on the left and PFS curve on the right.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7163556/v1/9a5114be160c95cfba5ec159.jpeg"},{"id":89976229,"identity":"9099ae6c-1788-49a6-9cb3-ae816834382b","added_by":"auto","created_at":"2025-08-27 06:00:38","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":80779,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of univariate analysis of PFS and OS in sALCL patients with different clinical characteristics\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7163556/v1/5feb9b7ec1eb3049f1d6030b.jpeg"},{"id":89976226,"identity":"a033c270-431b-4e1a-82a5-7f25c800753f","added_by":"auto","created_at":"2025-08-27 06:00:38","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":51047,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of multivariate analysis of PFS and OS in sALCL patients with different clinical characteristics\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7163556/v1/f5c8e2470bec4c2a39f7d381.jpeg"},{"id":92091573,"identity":"572d6af8-799a-4b07-8ff1-4931ce7575ca","added_by":"auto","created_at":"2025-09-24 13:47:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1259606,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7163556/v1/643dd340-0259-47d2-b7f2-6c4463f6b343.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical features and prognostic outcomes of systemic anaplastic large cell lymphoma in a Chinese multicenter study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAnaplastic large cell lymphoma (ALCL) is a highly aggressive and heterogeneous subtype of peripheral T-cell lymphoma, comprising about 2% of non-Hodgkin's lymphomas \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/sup\u003e. Strong expression of anaplastic lymphoma kinase (ALK) and CD30 defines ALK-positive ALCL (ALK\u0026thinsp;+\u0026thinsp;ALCL) \u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e. ALK, located on chromosome 2p23.2-p23.1, undergoes translocation with chromosome 5, forming the NPM::ALK fusion tyrosine kinase, which activates pathways driving cancer pathogenesis. For example, CD30 in \u003cem\u003eNPM::ALK\u003c/em\u003e-expressing cells triggers the NF-κB pathway and induces anti-apoptotic effects via p38/MAPK, promoting ALCL \u003csup\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/sup\u003e. However, subsequent studies have revealed that ALK expression is not the sole factor driving ALCL pathogenesis. Nonetheless, ALK expression serves as a defining characteristic of this group of disorders. Consequently, in 2016, the World Health Organization classified ALCL into ALK-positive (ALK\u0026thinsp;+\u0026thinsp;ALCL) and ALK-negative (ALK- ALCL) subtypes \u003csup\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/sup\u003e, each with distinct clinical features, diagnostic markers, and prognoses.\u003c/p\u003e\u003cp\u003eSeveral studies have found that ALK\u0026thinsp;+\u0026thinsp;ALCL is more common in individuals under 50 years of age. Its typical clinical manifestations include weight loss, fever, weakness, malaise, and night sweats. Additionally, it is often associated with peripheral or abdominal lymph node enlargement, extra-nodal infiltration, and bone marrow involvement \u003csup\u003e(\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e. Despite the advanced stage at diagnosis and diverse symptoms, many patients achieve remission with first-line treatments like CHOP, resulting in a 5-year overall survival rate of 70\u0026ndash;90% \u003csup\u003e(8\u0026ndash;10)\u003c/sup\u003e. In contrast, ALK- ALCL predominantly affects individuals aged 50 years or older. These patients less frequently present with lymph node enlargement or extra-nodal infiltration, and first-line treatments such as CHOP are generally ineffective. Their prognosis is poorer compared to ALK\u0026thinsp;+\u0026thinsp;ALCL, with a 5-year overall survival rate of only 30\u0026ndash;49% \u003csup\u003e(8, 11\u0026ndash;13)\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eDifferent ALCL subtypes exhibit distinct therapeutic outcomes and prognoses, making early diagnosis crucial. Molecular markers play a critical role in diagnosis and subtype classification of ALCL. Laurence et al. suggested that BCL6, CEBPB, and SERPINA1 are potential markers for ALK\u0026thinsp;+\u0026thinsp;ALCL, while CCR7 and CNTFR are indicative of ALK- ALCL \u003csup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/sup\u003e. Filippa et al. also proposed molecular markers; however, their application in clinical practice remains limited \u003csup\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn the 5th edition of the WHO Classification of Hematolymphoid Tumours, ALCL is subdivided into systemic ALK-positive ALCL (ALK\u0026thinsp;+\u0026thinsp;sALCL), systemic ALK-negative ALCL (ALK- sALCL), primary cutaneous ALCL, and breast implant-associated ALCL \u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e. While these subtypes share similar cytomorphologic and phenotypic features, they differ in genomic backgrounds and clinical courses \u003csup\u003e(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/sup\u003e. The prevalence of sALCL is low and remains under-investigated. Previous studies on sALCL were mostly based on small sample sizes, with significant variability between ALK\u0026thinsp;+\u0026thinsp;sALCL and ALK- sALCL, necessitating further research to enhance understanding of the disease. This study retrospectively examined 143 sALCL patients across 14 research centers in China to summarize their clinical features, immunohistochemical characteristics, therapeutic efficacy, and prognosis, providing insights into its clinical diagnosis, prognostic assessment, and treatment strategies.\u003c/p\u003e"},{"header":"2. Information and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Case information\u003c/h2\u003e\u003cp\u003eThis study collected data from 143 patients diagnosed with systemic anaplastic large-cell lymphoma (sALCL) between April 2010 and April 2022 from 14 study centers. The specific hospital names and the number of patients were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All patients were definitively diagnosed through pathological analysis, and their diagnosis conformed to the 2016 WHO classification criteria. Baseline data, retrieved from electronic medical records, included demographics (age, gender), comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, pathology and immunohistochemistry results, blood biochemistry, bone marrow aspiration, and imaging data such as CT/PET-CT, which were analyzed to determine the extent of lymph node involvement or extranodal lesions, the Ann Arbor stage, and the International Prognostic Index (IPI) for lymphoma. Based on the IPI score, patients were categorized into four risk groups: low risk (0\u0026ndash;1), low-intermediate risk (2), intermediate-high risk (3), and high risk (4\u0026ndash;5).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e14 study centers and number of patients.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHospital\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ethe People's Hospital of Hainan Province\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ethe Union Hospital of Fujian Medical University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ethe People's Hospital of Guangdong Province\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ethe Nanfang Hospital of Nanfang Medical University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ethe Shenzhen Municipal People's Hospital\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ethe First Affiliated Hospital of Kunming Medical University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ethe Shenzhen Hospital of Peking University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eKunhua Hospital of the First People's Hospital of Yunnan Province\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSun Yat-sen Memorial Hospital of Sun Yat-sen University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFujian Provincial Hospital\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ethe First Affiliated Hospital of Fujian Medical University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ethe Affiliated Hospital of Guangdong Medical University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ethe First Affiliated Hospital of Guangxi Medical University\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eZhuhai People's Hospital\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Treatment plan\u003c/h2\u003e\u003cp\u003eAmong the 143 patients, 135 received first-line chemotherapy, whereas 7 were treated with alternative regimens, including radiotherapy and steroid hormone therapy. Treatment data were unavailable for one patient. Among the patients who received first-line chemotherapy, three were excluded for not meeting the group treatment criteria. The remaining 132 patients underwent the following regimens: 61 received CHOP, 49 CHOPE, 9 BV\u0026thinsp;+\u0026thinsp;CHP, 5 CDOP, 5 P-GemOx, and one each received BFM-90, CVP, or Hyper-CVAD. Eight patients underwent intensive autologous hematopoietic stem cell transplantation (AHSCT) following remission from first-line treatment, and six achieved remission without relapse. Second-line chemotherapy was provided to patients who did not achieve remission with first-line treatment or experienced relapse.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Evaluation of efficacy\u003c/h2\u003e\u003cp\u003eRecent efficacy was assessed based on the International Lymphoma Efficacy Evaluation Criteria \u003csup\u003e(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/sup\u003e and classified as Complete Remission (CR), Partial Remission (PR), Stable Disease (SD), or Progressive Disease (PD). The complete response rate (CR rate) was calculated as CR / (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD\u0026thinsp;+\u0026thinsp;PD). The Overall Response Rate (ORR) was calculated as (CR\u0026thinsp;+\u0026thinsp;PR) / (CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD\u0026thinsp;+\u0026thinsp;PD).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Survival follow-up\u003c/h2\u003e\u003cp\u003eIn this study, patient survival data were primarily obtained from the electronic medical record system of the study center and through telephone follow-ups, with a cut-off date of December 2022. The primary outcomes were progression-free survival (PFS) and overall survival (OS). OS was defined as the time (in months) from the date of diagnosis to the date of death or last follow-up. PFS was defined as the time (in months) from the date of diagnosis to disease progression/recurrence, death, or last follow-up.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were conducted using SPSS 23.0 and R 4.4.1. The chi-square test or Fisher's exact test was applied for comparing categorical variables between groups. The Kaplan-Meier method was used to estimate median survival time and generate survival curves, while the log-rank test was applied to compare survival curves. Univariate and multivariate analyses were performed using the Cox proportional-hazards model. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Clinical information\u003c/h2\u003e\u003cp\u003eThe study cohort consisted of 143 patients, including 138 newly treated cases and 5 relapsed cases. The male-to-female ratio was 2.04:1. The median age of onset was 44 years (range: 13\u0026ndash;87). Among the 73 patients with extranodal involvement, the most commonly affected sites were the bone, lung, bone marrow, and skin. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the baseline characteristics of the 143 patients.\u003c/p\u003e\u003cp\u003ePatients were categorized into two groups: ALK-positive and ALK-negative. The median age was 33 years (range: 13\u0026ndash;85) in the ALK-positive group, with a mean age of 36\u0026thinsp;\u0026plusmn;\u0026thinsp;17 years, compared to a median age of 53 years (range: 15\u0026ndash;87) and mean age of 52\u0026thinsp;\u0026plusmn;\u0026thinsp;16 years in the ALK-negative group. ALK-negative patients were significantly older than ALK-positive patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). But no statistically significant differences were observed between the two groups in terms of gender, comorbidities, extranodal involvement, bone marrow findings, Ann Arbor stage, ECOG score, or IPI score (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient clinical characteristics.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of cases\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 (67.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47 (32.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;=60 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (21.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;60 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e113 (79.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbidities\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (25.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtranodal involvement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (51.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtranodal involvement\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (18.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (18.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnn Arbor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅠ-Ⅱ stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (25.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢ-Ⅳ stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e102 (71.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIPI scores\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003elow-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45 (31.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003elow-intermediate-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (33.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eintermediate-high-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (25.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehigh-risk group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (6.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemophagocytic Syndrome\u003c/p\u003e\u003cp\u003eALK\u003c/p\u003e\u003cp\u003epositive\u003c/p\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003cp\u003e80 (55.9%)\u003c/p\u003e\u003cp\u003e63 (44.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Blood biochemistry\u003c/h2\u003e\u003cp\u003eAmong the 143 patients, lactate dehydrogenase (LDH) levels were available for 142 patients; LDH was elevated in 123 patients (86.6%), including 6 patients with LDH\u0026thinsp;\u0026gt;\u0026thinsp;500 U/L. β2-microglobulin (β2-MG) levels were unavailable for 11 patients, but were elevated in 114 patients (86.4%). There was no statistically significant difference in the rates of elevated LDH and β2-MG between the ALK-positive and ALK-negative groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the differences in clinical characteristics and blood biochemistry between the two groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical characteristics and blood biochemistry of ALK-positive and ALK-negative sALCL patients.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eclinical characteristics/blood biochemistry\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eALK\u0026thinsp;+\u0026thinsp;sALCL\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eALK- sALCL\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian age\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33(13\u0026ndash;85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53(15\u0026ndash;87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.374\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.541\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtranodal involvement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.080\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.777\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone marrow involvement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.097\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.148\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnn Arbor Ⅲ/Ⅳ stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.909\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.199\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.655\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIPI\u0026thinsp;=\u0026thinsp;3\u0026ndash;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.289\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.591\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated LDH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eElevated β2-MG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.272\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.132\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: * indicates a statistically significant difference between the two groups.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Immunohistochemical characteristics\u003c/h2\u003e\u003cp\u003eThe majority of patients (98.6%) were CD30-positive, except for 4 patients who were not tested. All cases tested for Ki-67 demonstrated high expression, with a median value of 80.0%. Most cases tested for TdT and EBER yielded negative results. The ALK-positive group exhibited significantly higher positivity rates for TIA-1 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018, χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;5.568) and granzyme B (p\u0026thinsp;=\u0026thinsp;0.018, χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;5.622) compared to the ALK-negative group. The proportions of immunohistochemical markers in the ALK-positive and ALK-negative groups are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eImmunohistochemical characterization table.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmunohistochemistry\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eALK-positive group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eALK-negative group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTotal cases\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78(56.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59(42.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e137(98.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(0.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1(0.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2(1.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKi-67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69(56.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e54(43.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e123(100%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0(0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0(0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0(0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTdT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(8.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1(4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3(13.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(56.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(30.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20(87.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTIA-1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32(51.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19(30.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e51(82.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(3.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9(14.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11(17.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGranzyme B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25(54.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13(28.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e38(82.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(2.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(15.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(17.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEBER\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4(4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6(5.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003enegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54(53.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41(40.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95(94.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Efficacy evaluation\u003c/h2\u003e\u003cp\u003eAmong the 135 patients who received first-line chemotherapy, 90 patients achieved CR, 16 patients achieved PR, 7 patients were evaluated as having SD, and 22 patients were evaluated as having PD. The CR rate was 66.7%, and the ORR was 78.5%. The CR rate in the ALK-positive group was 71.0%, with an ORR of 80.3%, while the CR rate in the ALK-negative group was 61.0%, with an ORR of 76.3%. There was no statistically significant difference between the two groups.\u003c/p\u003e\u003cp\u003eIn this study, 61 patients received CHOP, with a CR rate of 54.0% and an ORR of 67.2%; 49 patients received CHOPE, with a CR rate of 81.6% and an ORR of 89.8%; and 9 patients received BV\u0026thinsp;+\u0026thinsp;CHP, with a CR rate of 77.7% and an ORR of 88.9%. The chi-square test results showed that the CR rate (χ2\u0026thinsp;=\u0026thinsp;9.726, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) and ORR (χ2\u0026thinsp;=\u0026thinsp;8.474, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) of the three chemotherapy regimens were significantly different, with a significant difference between CHOP and CHOPE, the latter being significantly superior to the former. However, there were no statistically significant differences between CHOP and BV\u0026thinsp;+\u0026thinsp;CHP, and between CHOPE and BV\u0026thinsp;+\u0026thinsp;CHP.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Prognostic analysis\u003c/h2\u003e\u003cp\u003eOf the 143 patients with sALCL, 134 patients had complete follow-up data, including 32 deaths and 102 survivors by the end of follow-up, while 9 patients were lost to follow-up, resulting in a follow-up rate of 93.7%. The median follow-up time for this study was 31 months (range: 0.1\u0026ndash;99.2 months), and the median OS and the median PFS were not reached. In the ALK-negative group, the median OS was 71.9 months, while the median PFS was not reached. In the ALK-positive group, both the median OS and median PFS were not reached.\u003c/p\u003e\u003cp\u003eLog-rank analysis revealed significant differences in the OS and PFS survival curves between the ALK-negative and ALK-positive groups, indicating that ALK-negativity was a risk factor for both OS and PFS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). When analyzing only sub-youth patients (aged\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;44 years), the ALK-negative group exhibited worse prognoses than the ALK-positive group, but the difference was not statistically significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCox univariate analysis identified ALK-negativity, age\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;60 years, elevated β2-MG, and failure to achieve CR with first-line treatment as risk factors for PFS. For OS, bone marrow infiltration is a risk factor rather than elevated β2-MG (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Multivariate analysis revealed that elevated β2-MG and failure to achieve CR with first-line treatment were independent poor prognostic factors for PFS, while for OS, additional independent factors included age\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;60 years and bone marrow involvement, but not elevated β2-MG (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eSystemic anaplastic large cell lymphoma (sALCL) is a malignant lymphoma defined by its pronounced aggressiveness and significant heterogeneity. It consists of distinctive large pleomorphic lymphoid cells with abundant cytoplasm and nuclei shaped like horseshoes. Based on ALK expression, sALCL is categorized into ALK-positive and ALK-negative subtypes, which differ in clinical symptoms, treatment responses, and prognoses, with their diagnostic markers yet to be fully established \u003csup\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/sup\u003e. Consequently, distinguishing between the two subtypes based solely on ALK expression is challenging, and relying on ALK expression alone to evaluate therapeutic efficacy and prognosis is imprecise. Thus, further insights into the clinical characteristics, therapeutic outcomes, prognostic factors, and molecular features of sALCL are essential to optimize diagnostic and therapeutic strategies.\u003c/p\u003e\u003cp\u003eIn terms of clinical features, this study found that male patients were predominant, with a median onset age of 44 years. The majority of patients were in advanced stages (Ann Arbor stage III-IV), representing 71.3% of cases at the time of consultation. Approximately 25.2% of patients had comorbidities, with extranodal involvement observed in 51.0% at initial treatment, and \u0026gt;\u0026thinsp;=\u0026thinsp;2 extranodal sites involved in 37.0% of cases. The most frequently involved sites were bone, lung, bone marrow, and skin. These findings are broadly consistent with prior studies on sALCL \u003csup\u003e(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/sup\u003e. Multiple studies have demonstrated a higher prevalence of ALK\u0026thinsp;+\u0026thinsp;sALCL compared to ALK- sALCL \u003csup\u003e(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/sup\u003e. Age is among the most significant distinguishing factors between the two subtypes. ALK\u0026thinsp;+\u0026thinsp;sALCL primarily affects younger individuals, whereas most patients with ALK- sALCL are aged 40 to 65. Our study observed a slightly higher number of patients with ALK\u0026thinsp;+\u0026thinsp;sALCL compared to ALK- sALCL. Furthermore, patients with ALK\u0026thinsp;+\u0026thinsp;sALCL were significantly younger than those with ALK- sALCL, with a statistically significant difference between the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), consistent with prior findings.\u003c/p\u003e\u003cp\u003eIt has been reported that ALK\u0026thinsp;+\u0026thinsp;ALCL patients are more likely to exhibit bone marrow involvement \u003csup\u003e(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/sup\u003e; however, this was not statistically significant in our study. Moreover, no statistically significant differences were observed between the two groups in terms of gender, comorbidities, incidence of extranodal involvement, Ann Arbor staging, ECOG, or IPI scores, findings that align with previous studies. Furthermore, our study revealed that β2-MG, a biochemical marker indicative of tumor burden, was more frequently elevated in the ALK\u0026thinsp;+\u0026thinsp;sALCL group. Although consistent with trends observed in a retrospective study of sALCL \u003csup\u003e(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/sup\u003e, the differences in our findings were not statistically significant, warranting further investigation. Similarly, our findings regarding the proportion of elevated LDH, which showed no statistically significant differences between the groups, were consistent with previous studies.\u003c/p\u003e\u003cp\u003eAll ALCLs share common morphological, immunophenotypic, and gene expression features; however, ALCL represents a heterogeneous group of clinicopathologic entities rather than a single disease \u003csup\u003e(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/sup\u003e. Immunohistochemical analysis plays a critical role in the accurate diagnosis of sALCL. In this study, the vast majority of patients were found to be CD30 positive with high Ki-67 expression. Additionally, most patients were positive for TIA-1 and granzyme B, while the majority were negative for TdT and EBER in tumor cells, suggesting that the development of ALCL is not associated with Epstein-Barr virus (EBV) infection. These findings are largely consistent with previous studies \u003csup\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/sup\u003e. A comparison between the ALK\u0026thinsp;+\u0026thinsp;sALCL group and the ALK- sALCL group revealed significantly higher positivity rates for TIA-1 and granzyme B in the former. This finding aligns with conclusions from multiple domestic and international studies. Furthermore, cytotoxic molecules such as TIA-1 and granzyme B have been utilized as markers to differentiate ALK\u0026thinsp;+\u0026thinsp;sALCL from other lymphomas \u003csup\u003e(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAnthracycline-containing multidrug regimens remain the gold standard for treating sALCL. The National Comprehensive Cancer Network (NCCN) guidelines recommend treatment regimens such as BV combined with CHP, CHOP, CHOEP, dose-adjusted EPOCH, and autologous stem cell transplantation as first-line consolidation therapies. Numerous studies, including ours, have demonstrated that CHOPE significantly improves event-free survival in ALCL patients \u003csup\u003e(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/sup\u003e. Our study reported a CR rate of 54.0% and an ORR of 67.2% with CHOP, a CR rate of 81.6% and an ORR of 89.8% with CHOPE, and a CR rate of 77.7% and an ORR of 88.9% with BV\u0026thinsp;+\u0026thinsp;CHP. Among these regimens, CHOPE demonstrated significantly greater efficacy compared to CHOP. However, due to increased toxicity, CHOPE is primarily reserved for younger patients with ALK\u0026thinsp;+\u0026thinsp;sALCL. BV\u0026thinsp;+\u0026thinsp;CHP exhibited notable therapeutic effects and outperformed CHOP in our study, consistent with the ECHELON-2 study \u003csup\u003e(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/sup\u003e; however, the results were not statistically significant, likely due to sample size limitations. Hematopoietic stem cell transplantation is widely recommended as a first-line consolidation therapy for patients with ALK- sALCL and high-risk ALK\u0026thinsp;+\u0026thinsp;sALCL \u003csup\u003e(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/sup\u003e. In our study, eight patients underwent autologous hematopoietic stem cell transplantation (AHSCT) after achieving remission with first-line therapy, and six remained relapse-free, demonstrating satisfactory outcomes. Given the relatively poor efficacy in treating ALK- sALCL, some studies have attempted intensified chemotherapy regimens or novel drug combinations with CHOP, such as hyper-CVAD, but these approaches have shown limited success \u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e. Nevertheless, combining novel agents, such as ALK inhibitors and CD30 monoclonal antibodies, with CHOP regimens represents an emerging trend in ALCL treatment \u003csup\u003e(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/sup\u003e. Thus, the integration of novel drugs with CHOP regimens is expected to become a focal point in future ALCL research.\u003c/p\u003e\u003cp\u003eNumerous studies have investigated the prognostic factors influencing sALCL. Among these, the relationship between ALK expression and the prognosis of sALCL patients has been extensively studied, but its prognostic value remains controversial. Overall, ALK\u0026thinsp;+\u0026thinsp;sALCL patients are generally believed to have a better prognosis than those with ALK- sALCL. One study reported a 5-year survival rate of 70\u0026ndash;86% for ALK\u0026thinsp;+\u0026thinsp;sALCL patients, compared to only 30\u0026ndash;49% for ALK- sALCL patients \u003csup\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/sup\u003e. Furthermore, the 5-year overall survival (OS) of treated ALK\u0026thinsp;+\u0026thinsp;sALCL patients was 70\u0026ndash;90%, compared to 40\u0026ndash;60% for ALK- sALCL patients \u003csup\u003e(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/sup\u003e. However, it has been suggested that these differences may be attributed to variations in age of onset and staging. When controlling for factors such as age and stage, no significant prognostic differences were observed between ALK\u0026thinsp;+\u0026thinsp;and ALK- sALCL patients \u003csup\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/sup\u003e. Nonetheless, a subgroup survival analysis of sALCL patients under 40 years revealed that even within this age group, the difference in OS between the two groups remained statistically significant \u003csup\u003e(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/sup\u003e. In our study, ALK-negativity emerged as a significant risk factor for both OS and PFS across all age groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, in patients younger than young adults, ALK-negativity still exhibited a trend toward poorer prognosis, though the difference was not statistically significant. ALK expression also was excluded from the multivariate analysis. Additionally, failure to achieve CR with first-line therapy was identified as independent risk factor for OS and PFS. Age\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;60 years and bone marrow involvement were an independent risk factors for OS, while elevated β2-MG was an independent risk factor for PFS. Among these, bone marrow involvement as an adverse prognostic factor for OS has been confirmed in a retrospective study and several reviews \u003csup\u003e(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis study collected data from 143 patients with sALCL through a multicenter collaboration, enabling a more representative retrospective analysis. In summary, this study represents a multicenter effort with one of the largest sample sizes in this field. Our findings indicate that sALCL predominantly affects males and is characterized by extranodal involvement, serological abnormalities, and specific immunohistochemical features. Significant differences were observed between ALK-negative and ALK-positive patients in certain clinical features. CHOP(E) remains the most widely used first-line treatment option, demonstrating favorable outcomes. Failure to achieve CR with first-line therapy was identified as an independent adverse prognostic factor for PFS and OS. Additionally, age\u0026thinsp;\u0026ge;\u0026thinsp;60 years and bone marrow involvement independently impacted OS, while elevated β2-MG independently impacted PFS. The prognostic impact of ALK expression requires further investigation, accounting for potential confounding factors. Although this study included a large sample size, most cases originated from southeastern China, and inherent limitations of retrospective analysis necessitate further prospective studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003ethe authors have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003ePatient consent statement\u003c/h2\u003e\u003cp\u003e The informed consent was waived considering the retrospective nature of the study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003cp\u003e The study was approved by the institutional review board of First Affiliated Hospital of Guangxi Medical University (Y2025361) and each participating center, waiving the requirement for patient consent.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eDuring the course of this research, we did not receive any form of financial support. All required funding was provided by the researchers personally or by their affiliated institutions.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eR.H., J.M., S.Z. and M.Z. conceived and designed the study. S.Z., J.L., H.Y., M.W. and G.C. collected data. S.Z., M.Z, Z.W., K.C., D.Q. and Z.P. did statistical analysis and clinical interpretation. M.Z. and Z.W. drafted initial manuscript. All the authors critically reviewed the manuscript. All the authors read and approved the final report.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank all patients involved in this study at 14 medical centers.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e\u003cp\u003eAll data supporting the findings of this study are available within the paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eA clinical evaluation of the International Lymphoma Study Group. classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997;89(11):3909\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. 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J Clin oncology: official J Am Soc Clin Oncol. 2012;30(18):2190\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126(1):17\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWei C, Zhao DQ, Zhang Y, Wang W, Zhang W, Zhou DB. Clinical characteristics and prognostic analysis of 48 cases of primary systemic anaplastic large cell lymphoma. J Clin Hematol. 2022;35(01):52\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDoghri R, HadjKacem LB, Houcine Y, Charfi L, Driss M, Kacem K, et al. Prognostic factors of ALK-negative anaplastic large-cell lymphoma: a single-institution experience. Ann Hematol. 2018;97(4):725\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"systemic anaplastic large cell lymphoma, clinical characteristics, prognostic analysis, multi-center study","lastPublishedDoi":"10.21203/rs.3.rs-7163556/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7163556/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThe prevalence of systemic anaplastic large cell lymphoma (sALCL) is low and remains under-investigated. This study aimed to investigate the clinical features, treatment outcomes, and prognostic factors of sALCL.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective analysis of 143 sALCL patients treated at 14 centers from 2010 to 2022 was conducted.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe median age was 44 years, with a male predominance. Most patients were diagnosed at an advanced stage, and extranodal involvement, particularly in the bone, was observed in 51.0% of cases. Most patients exhibited elevated LDH, β2-MG, CD30 positivity, and high Ki-67 expression. ALK-positivity was found in 55.9% of patients, who were significantly younger than ALK-negative patients (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). First-line chemotherapy achieved a complete response (CR) rate of 66.7% and an overall response rate (ORR) of 78.5%. CHOPE was more effective than CHOP. Failure to achieve complete response, age\u0026thinsp;\u0026ge;\u0026thinsp;60 years, bone marrow involvement, and elevated β2-MG were identified as independent prognostic factors for survival.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis study highlights the unique distinct clinical and molecular features of sALCL in the real world of China and suggests that ALK expression and treatment regimen significantly influence outcomes, providing new data for clinical practice.\u003c/p\u003e","manuscriptTitle":"Clinical features and prognostic outcomes of systemic anaplastic large cell lymphoma in a Chinese multicenter study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 06:00:33","doi":"10.21203/rs.3.rs-7163556/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":"3471d135-db3c-408e-a4ae-f41e7d74008b","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-24T13:39:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-27 06:00:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7163556","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7163556","identity":"rs-7163556","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}