Chidamide-BEAM Conditioning plus Autologous Stem Cell Transplantation for T-cell Lymphoma: A Single-Arm, Single-Center, Phase 2 Trial

Chidamide-BEAM Conditioning plus Autologous Stem Cell Transplantation for T-cell Lymphoma: A Single-Arm, Single-Center, Phase 2 Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Chidamide-BEAM Conditioning plus Autologous Stem Cell Transplantation for T-cell Lymphoma: A Single-Arm, Single-Center, Phase 2 Trial Meng-Meng Ji, yige shen, Si-Yuan Chen, Rong-Ji Mu, Hui-Ying Li, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9258298/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 7 You are reading this latest preprint version Abstract This clinical trial (NCT05367856) evaluated the Chi-BEAM conditioning regimen followed by frontline autologous stem cell transplantation (ASCT) and chidamide maintenance in T-cell lymphoma (TCL). This study screened and enrolled 23 TCL patients between June 15, 2022, and June 15, 2023. Eligible participants were aged 18–65 years, had histological diagnosis of TCL (excluding ALK-positive anaplastic large cell lymphoma with International Prognostic Index [IPI] score 0–1), and achieved complete remission (CR) or partial remission (PR) after first-line chemotherapy. All enrolled patients received Chi-BEAM followed by ASCT and chidamide maintenance for 2 years, initiated after hematopoietic recovery. The primary endpoint was 2-year progression-free survival (PFS) rate. Secondary endpoints were 2-year overall survival (OS) rate, CR rate, time to hematopoietic reconstruction, and transplantation-related adverse events. At analysis, all 23 patients were alive. Median follow-up was 24.6 months (range, 18.2–38.7 months). The 2-year PFS and OS rates were 95.7% (95% CI, 72.9%-99.4%) and 100.0% (95% CI, 100.0%-100.0%), respectively. Grade 3–4 non-hematological adverse events included infection (13.0%), hepatic toxicity (8.7%), vomiting (4.3%), and mucositis (4.3%). The Chi-BEAM regimen with frontline ASCT followed by chidamide maintenance represents a potentially effective and well-tolerated treatment strategy for TCL, showing promising survival outcomes and a manageable safety profile. Biological sciences/Cancer/Cancer therapy/Targeted therapies Biological sciences/Cancer/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/T-cell lymphoma Figures Figure 1 Figure 2 Introduction T-cell lymphoma (TCL) represents a rare and heterogeneous subset of non-Hodgkin’s lymphomas (NHL), accounting for approximately 5–10% of NHL cases in Western countries and 15–20% in Asia [ 1 ]. There are many pathological types of TCL, including nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI), peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), and anaplastic large-cell lymphoma (ALCL) [ 2 ]. The intrinsic diversity and rarity of TCL complicates the diagnostic process, necessitating a comprehensive judgment according to multiple examination results, such as pathological examination, immunohistochemistry, gene rearrangement, and imaging examination [ 3 ]. The current treatment efficacy of TCL is unsatisfactory due to the lack of targeted treatment strategies [ 4 ]. First-line TCL treatment is still mainly as the CHOP regimen, following the treatment framework for B-cell NHL, with poor clinical outcomes [ 2 ]. Recent advances in molecular pathogenesis and genomic profiling have stimulated the discovery and clinical application of molecular biomarkers in TCL subtypes, enabling personalized care for TCL patients [ 5 ]. Epigenetic modifiers, including histone deacetylation (HDAC) inhibitors and hypomethylating agents, in the relapsed setting and in combination with chemotherapy in the front-line setting, have been demonstrated to improve the clinical efficacy of TCL treatment [ 6 ]. HDAC inhibitors activate the acetylation of histones, change the chromatin structure, modulate the accessibility of transcription factors to their target, promote the expression of tumor-suppressor genes, and induce anti-tumor activity [ 7 , 8 ]. Chidamide is a selective inhibitor of HDAC1, 2, 3, and 10 and could improve treatment efficacy in relapsed/refractory TCL [ 9 ]. Autologous stem cell transplantation (ASCT) is a therapeutic strategy for TCL patients in the first remission. The 2-year progression-free survival (PFS) rate with CHOP-based induction followed by ASCT was 52.9% in a prospective study [ 10 ]. Despite progress in molecular subtyping and therapeutic effect [ 11 ], prognosis of TCL patients requires further improvement in the era of ASCT [ 12 ]. Since BEAM (carmustine, etoposide, cytarabine, and melphalan) is the standard conditioning regimen for ASCT [ 13 ], optimizing the pretreatment plan and maintenance approach is crucial for enhancing the efficacy of TCL management. Given the therapeutic effect of chidamide in TCL [ 9 ], adding chidamide to the ASCT pretreatment and maintenance regimen may improve clinical efficacy. Therefore, this study was conducted to evaluate the effect and safety of the chidamide-BEAM (Chi-BEAM) regimen followed by front-line ASCT and chidamide maintenance in TCL patients. Subjects and Methods Study Design and Participants This single-arm, single-center, phase 2 trial (NCT05367856) was conducted at Ruijin Hospital in China, from June 15, 2022, and June 15, 2023. Eligible patients were aged 18–65 years and histologically diagnosed as TCL, excluding IPI 0–1 ALK+ anaplastic lymphoma, with complete remission (CR) or partial remission (PR) after first-line chemotherapy. Furthermore, eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, no serious organic lesions in the main organs, and met the requirements of the following laboratory examination indicators (conducted within 7 days before treatment): 1. white blood cell count ≥ 3.0 × 10 9 /L, absolute neutrophil count ≥ 1.5 × 10 9 /L, hemoglobin ≥ 90g/L, platelets ≥ 75 × 10 9 /L; 2. total bilirubin ≤ 1.5 × the upper limit of normal (ULN); 3. aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5× the ULN; and 4. normal creatinine clearance rate. Furthermore, eligible patients had no prior history of malignancy, no heart dysfunction, and a life expectancy of at least 3 months. Participants were required to provide written informed consent before the study. Patients were excluded if they had previous bone marrow transplantation; other malignant tumors within the past five years; or uncontrollable cardiocerebrovascular, coagulative, autoimmune, or serious infectious disease. Those who were HBsAg, HCV, or HIV positive were also excluded. HBV and HCV serological positivity were allowed; however, DNA/RNA testing was required to be negative. Those with a left ventricular ejection fraction (LVEF) of 50% or less, mental illness, or who were suspected to be unable to fully comply with the study protocol were also excluded, as were pregnant or lactating women and patients with an uncontrollable medical condition that researchers believed would affect their participation in the study. Treatment response was assessed according to standardized criteria for non-Hodgkin lymphoma. This study was conducted according to the principles of the Declaration of Helsinki. The final version of the protocol was reviewed and approved by an independent ethics committee. All patients gave written informed consent. This study is registered with ClinicalTrials.gov (NCT05367856) and is closed to new participants. Procedures All patients received Chi-BEAM followed by ASCT. The regimens comprised 30 mg chidamide administered orally on D-7, D-4, D-1, and D + 3, 300 mg/m 2 carmustine administered intravenously on D-7, 100 mg/m 2 etoposide administered intravenously every 12 hours on D-6-D-3, 200 mg/m 2 /d cytarabine administered intravenously every 12 hours on D-6-D-3, and 140 mg/m 2 melphalan administered intravenously on D-2. The day of stem cell reinfusion was designated D0. Granulocyte-colony stimulating factor was administered if the absolute neutrophil count was less than 0.5 × 10 9 cells/L after hematopoietic stem cell transfusion. Platelet transfusions were permitted at the discretion of the investigator when the platelet count was less than 20 × 10 9 cells/L. Supportive medications and other blood product transfusions were provided according to local protocols. Outcomes The primary endpoint was 2-year PFS rate, defined as the proportion of patients who were alive and free from disease progression at 2 years after randomization. The secondary endpoints included 2-year overall survival (OS) rate (the proportion of patients who were alive at 2 years after randomization), CR rate (the percentage of participants with complete response was determined using the 2014 Lugano criteria), the time of hematopoietic reconstruction, and transplantation-related adverse events. The first day of neutrophil counts ≥ 0.5 × 10 9 /L for 3 consecutive days was the time of successful implantation of granulocytes. The first day of platelet counts ≥ 20.0 × 10 9 /L for 7 consecutive days without platelet infusion was considered the successful megakaryocyte implantation time. Statistical Analysis As reported previously [ 10 ], the 2-year PFS rate for TCL patients was conservatively set at 52.9%. Chi-BEAM pretreatment was expected to increase the 2-year PFS rate to 81% after ASCT. To achieve 90% power at a one-sided 0.025 significance, we required an overall sample size of 23 patients, assuming a dropout rate of 8%, according to PASS software calculations. The study duration was determined to be 3 years, with patients’ accrual occurring within the first 2 years. PFS was defined as the time from the date of transplantation to the date of disease progression, relapse, or death from any cause, whichever occurred first. OS was defined as the time from the date of transplantation to the date of death from any cause. Patients who were lost to follow-up or who had not experienced an event by the end of the study period were censored at the time of their last known follow-up. Survival curves were estimated using the Kaplan-Meier method, and comparisons between groups were performed with the log-rank test. All statistical analyses were performed using IBM SPSS Statistics, Version 26.0, and a two-sided p-value < 0.05 was considered statistically significant. Results Participant Characteristics Between June 15, 2022, and June 15, 2023, a total of 26 patients were screened for eligibility, of whom 2 withdrew consent and 1 experienced mobilization failure. Consequently, 23 patients were enrolled and proceeded to transplantation. A flow chart of the study is shown in Fig. 1 . The intention-to-treat population (ITTP) of 23 patients included: PTCL-NOS (n = 6; 26.1%), ALK-negative ALCL (n = 6; 26.1%), and nTFHL-AI (n = 11; 47.8%); 56.5% of the patients were men, and the median age was 49 years (range, 22 to 65 years). Regarding disease characteristics, 95.7% of the patients presented with advanced stage disease, 87.0% with elevated serum lactate dehydrogenase, and 47.8% with B symptoms. The baseline clinical and pathological characteristics are summarized in Table 1. Survival At the time of analysis, all 23 enrolled patients were alive. The median follow-up of surviving patients was 24.6 months (range, 18.2 to 38.7 months). In the ITTP, the 2-year PFS and OS rates were 95.7% (95% CI, 72.9–99.4) and 100.0% (95% CI, 100.0-100.0), respectively (Fig. 2 A-B). When analyzed by pathological subtyping, the 2-year PFS rates were 100% in ALCL, 100% in PTCL-NOS, and 88.9% in nTFHL-AI, with a 2-year OS of 100% across all these subtypes (Fig. 2 C-D). Remission rates At 3 months post-transplantation, 17 (73.9%) patients had achieved CR and 5 (21.7%) had achieved PR. Subsequently, one patient (4.3%) experienced relapse or disease progression within the initial two-year period, or more precisely, at 4.4 months post-transplantation. Clonality analysis conducted at the time of relapse confirmed the same malignant clone as identified at initial diagnosis. This case, characterized by high-risk mutations in TET2 , RHOA , and IDH2 and classified as the T1 subtype [ 11 ], likely contributed to the poor response to transplantation. No transplant-related mortality was reported until the last follow-up. Hematopoietic reconstitution The median time for neutrophil engraftment was 10 days, and for megakaryocytic engraftment was 16 days. The post-transplant period was characterized by significant cytopenias, with a high incidence of febrile agranulocytosis (82.6%, 19/23), which had a median duration of 4 days; the median duration of severe (Grade 4) agranulocytosis and athrombocytopenia was 8 and 10 days, respectively. Supportive care requirements were notable for platelet transfusions (median 4 units), while red blood cell transfusions were minimal (median 0.5 units), consistent with the low incidence of severe anemia (13%, 3/23, Table 2). Transplantation-related Adverse Events Grades 3 to 4 hematologic toxicities were seen in 100% of patients, whereas grades 3 to 4 non-hematologic toxicities were recorded in 4 patients (17.4%), with infectious complications as the most frequent adverse event (n = 3; 13.0%), followed by hepatic (n = 2; 8.7%), vomiting (n = 1; 4.3%), and mucositis (n = 1; 4.3%). No patients died due to adverse events (Table 3). Discussion ASCT is an important consolidation strategy for TCL in first remission and has been shown to enhance therapeutic efficacy [ 12 ]. The recommendation for ASCT is based on the findings of several prospective and retrospective studies. The largest prospective study, Nordic Lymphoma Group (NLG)-T-01, revealed that dose-dense induction followed by ASCT is well tolerated and results in better outcomes for transplantation-eligible patients with PTCL (Table 4) [ 10 ]. Similarly, a multi-center retrospective analysis by the GELTAMO/FIL group reported significantly improved 5-year PFS and OS in patients undergoing upfront ASCT compared with those who did not, reinforcing the role of ASCT as consolidation therapy in PTCL (Table 5) [ 14 ]. Therefore, ASCT is consolidated as a standard of care for TCL in the first remission. The BEAM regimen remains the most widely used conditioning regimen before ASCT in TCL patients. However, optimizing this conditioning strategy is essential to further enhance treatment efficacy, particularly given the substantial proportion of patients who still experience disease relapse post-ASCT [ 10 , 14 ]. Chidamide, an orally available HDAC inhibitor selectively targeting HDAC1, 2, 3, and 10, has been approved in China both as monotherapy and in combination regimens for TCL [ 15 – 18 ]. Preclinical and clinical studies have shown that chidamide exerts anti-tumor effects through multiple mechanisms, including inhibition of cell proliferation, induction of G0/G1 cell cycle arrest [ 19 ], promotion of apoptosis [ 20 ], and sensitization to chemotherapy [ 21 ] across various hematologic malignancies. For instance, chidamide can enhance the cytotoxicity of cytarabine in CD34 + acute myeloid leukemia cells by suppressing proliferation, increasing apoptosis, and reinforcing cell cycle arrest in vitro [ 22 ]. Clinically, combinations such as chidamide with etoposide, prednisone, and thalidomide have improved PFS and OS in previously untreated nTFHL-AI patients [ 23 ]. These findings provide a strong rationale for integrating chidamide with chemotherapeutic agents. Given the established efficacy of chidamide in TCL, its incorporation into the ASCT conditioning regimen represents a rational approach to improve transplant outcomes. The exploration of novel chidamide-containing conditioning regimens has yielded promising outcomes in patients undergoing ASCT. For high-risk, relapsed/refractory lymphoma, the Chi-CGB regimen achieved PFS of 80.6% and OS of 86.1% [ 24 ]. Similarly, the Chi-BEAC regimen demonstrated comparable efficacy, with 2-year PFS and OS as 81.1% and 86.1% OS, respectively [ 25 ]. However, no study to date has systematically optimized the classic BEAM backbone with chidamide. Our findings directly address this unmet need. In our cohort of 23 transplantation-eligible TCL patients, the Chi-BEAM regimen yielded outstanding outcomes: at a median follow-up of 24.6 months, the 2-year PFS and OS were 95.7% and 100.0%, respectively. Notably, this promising efficacy was consistently observed across key pathological subtypes, including ALCL, PTCL-NOS, and nTFHL-AI. When compared with historical data using standard BEAM (Table 4), the Chi-BEAM regimen appears to confer a substantial survival advantage, providing the first clinical evidence that addition of chidamide into the established BEAM backbone is not only feasible but also lead to superior transplant outcomes. Our study has limitations. The single-arm design and small sample size prevent definitive conclusions regarding the magnitude of benefit attributable to chidamide, taking account that TCL is a rare entity of NHL. Potential toxicities from combining chidamide with intensive chemotherapy require further monitoring, and longer follow-up is needed to assess long-term survival and late relapse. In conclusion, the Chi-BEAM regimen represents a promising and rationally designed conditioning strategy that demonstrates remarkable efficacy and a manageable safety profile. It is worthy of rigorous clinical evaluation in larger, randomized controlled trials involving transplantation-eligible TCL patients. Declarations Acknowledgments The authors thank the patients and their families, as well as the participating study teams, for making this study possible. This work was partially supported by research funding from the National Key R&D Program of China (2022YFC2502600 and 2023YFC3605704), the National Natural Science Foundation of China (82470173, 82200201, 82130004, 82170178 and 82070204), the Chang Jiang Scholars Program, Shanghai Lymphoma Clinical Cohort of Shanghai Hospital Development Center (SHDC2025CCS008), the Multicenter Hematology-Oncology Program Evaluation System (M-HOPES), the Shanghai Sailing Program (23YF1423700), Collaborative Innovation Center of Systems Biomedicine, Hainan Provincial Natural Science Foundation (2026-387), Hainan Provincial Joint Project for Health and Health Technology Innovation (2026-71), Medical Engineering Cross Project of Shanghai Jiaotong University. Author contributions MMJ conceived, designed, directed and supervised the study and wrote the manuscript. YGS wrote the protocol, collected and analyzed clinical data, and wrote the manuscript. SYC, and HYL collected and analyzed clinical data. RJM was responsible for the statistical review. LW, SC, PPX, ZZ, LDZ, HJZ, MCC, YHH, DF, YJ H, WT recruited patients. Declaration of interests All authors declare that they have no competing interests. Data sharing All sequencing data (including Whole Exome Sequencing) have been deposited in the GSA-Human database and can be accessed through the following link: https://bigd.big.ac.cn/gsa-human/browse/HRA004246. It is available by contacting the lead contact, Meng-Meng Ji ( [email protected] ), upon request. References Mulvey E, Ruan J. Biomarker-driven management strategies for peripheral T cell lymphoma. J Hematol Oncol. 2020;13:59. Shea L, Mehta-Shah N. Peripheral T-cell lymphoma: are all patients high risk? Blood. 2024;144:2604–12. Marchi E, O'Connor OA. The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management. CA Cancer J Clin. 2020;70:47–70. Ma H, Marchi E, O'Connor OA. The peripheral T-cell lymphomas: an unusual path to cure. Lancet Haematol. 2020;7:e765-e71. Huang Z, Fu Y, Yang H, Zhou Y, Shi M, Li Q, et al. Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application. Mol Cancer. 2024;23:36. Luan Y, Li X, Luan Y, Luo J, Dong Q, Ye S, et al. Therapeutic challenges in peripheral T-cell lymphoma. Mol Cancer. 2024;23:2. Wang P, Wang Z, Liu J. Role of HDACs in normal and malignant hematopoiesis. Mol Cancer. 2020;19:5. Shi MQ, Xu Y, Fu X, Pan DS, Lu XP, Xiao Y, et al. Advances in targeting histone deacetylase for treatment of solid tumors. J Hematol Oncol. 2024;17:37. Izykowska K, Rassek K, Korsak D, Przybylski GK. Novel targeted therapies of T cell lymphomas. J Hematol Oncol. 2020;13:176. d'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30:3093–9. Huang YH, Qiu YR, Zhang QL, Cai MC, Yu H, Zhang JM, et al. Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes. Cell Rep Med. 2024;5:101416. Brink M, Meeuwes FO, van der Poel MWM, Kersten MJ, Wondergem M, Mutsaers P, et al. Impact of etoposide and ASCT on survival among patients aged < 65 years with stage II to IV PTCL: a population-based cohort study. Blood. 2022;140:1009–19. Du J, Yu D, Han X, Zhu L, Huang Z. Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4:e219807. Garcia-Sancho AM, Bellei M, Lopez-Parra M, Gritti G, Cortes M, Novelli S, et al. Autologous stem-cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: a multicenter GELTAMO/FIL study. Haematologica. 2022;107:2675–84. Shi Y, Jia B, Xu W, Li W, Liu T, Liu P, et al. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol. 2017;10:69. Pang Z, Wang Y, Liu Z, Zhang S, Wei C, Xu Z, et al. Linperlisib Plus Chidamide in Relapsed or Refractory Cutaneous T-Cell Lymphoma: A Nonrandomized Clinical Trial. JAMA Dermatol. 2025;161:923–30. Atallah-Yunes SA, Wang Y. Dual epigenetic therapy plus chemotherapy in peripheral T cell lymphoma with T follicular helper phenotype. Med. 2024;5:1335–7. Ding K, Liu H, Yang H, Zhu H, Ma J, Peng H, et al. A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma. Med. 2024;5:1393 – 401 e2. Gu S, Hou Y, Dovat K, Dovat S, Song C, Ge Z. Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia. Exp Hematol Oncol. 2023;12:23. Wang H, Liu YC, Zhu CY, Yan F, Wang MZ, Chen XS, et al. Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway. J Exp Clin Cancer Res. 2020;39:278. Zhao H, Jiang Y, Lin F, Zhong M, Tan J, Zhou Y, et al. Chidamide and apatinib are therapeutically synergistic in acute myeloid leukemia stem and progenitor cells. Exp Hematol Oncol. 2022;11:29. Li Y, Wang Y, Zhou Y, Li J, Chen K, Zhang L, et al. Cooperative effect of chidamide and chemotherapeutic drugs induce apoptosis by DNA damage accumulation and repair defects in acute myeloid leukemia stem and progenitor cells. Clin Epigenetics. 2017;9:83. Wang Y, Zhang M, Song W, Cai Q, Zhang L, Sun X, et al. Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T-cell lymphoma in a Chinese population: A multicenter phase II trial. Am J Hematol. 2022;97:623–9. Ji J, Liu Z, Kuang P, Dong T, Chen X, Li J, et al. A new conditioning regimen with chidamide, cladribine, gemcitabine and busulfan significantly improve the outcome of high-risk or relapsed/refractory non-Hodgkin's lymphomas. Int J Cancer. 2021;149:2075–82. Xia Y, Wang L, Ding K, Wu J, Yin H, Hu M, et al. Chidamide-BEAC plus autologous stem cell transplantation in high-risk non-Hodgkin lymphoma: a phase II clinical trial. Chin Med J (Engl). 2023;136:1491–3. Tables Tables are available in the Supplementary Files section. Additional Declarations The authors have declared there is NO conflict of interest to disclose. Supplementary Files ChidamideTables.xlsx Tables StudyProtocol.docx Study Protocol Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 24 Apr, 2026 Review # 1 received at journal 17 Apr, 2026 Reviewer # 1 agreed at journal 30 Mar, 2026 Reviewers invited by journal 30 Mar, 2026 Submission checks completed at journal 30 Mar, 2026 Editor assigned by journal 29 Mar, 2026 First submitted to journal 29 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hui-Juan","middleName":"","lastName":"Zhong","suffix":""},{"id":614826563,"identity":"696594b3-62b6-4118-bc2d-d67dc0c3dcc7","order_by":11,"name":"Ming-Ci Cai","email":"","orcid":"","institution":"Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ming-Ci","middleName":"","lastName":"Cai","suffix":""},{"id":614826564,"identity":"d3317750-f85c-4026-a13c-bfe205c20eaf","order_by":12,"name":"Yao-Hui Huang","email":"","orcid":"","institution":"Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yao-Hui","middleName":"","lastName":"Huang","suffix":""},{"id":614826565,"identity":"906a32c9-8a22-4771-bb6d-45b660f21373","order_by":13,"name":"Di Fu","email":"","orcid":"","institution":"Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Di","middleName":"","lastName":"Fu","suffix":""},{"id":614826566,"identity":"d00c4cd0-ded3-41b7-b178-1a50c5e03d15","order_by":14,"name":"Yu-Jia Huo","email":"","orcid":"","institution":"Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yu-Jia","middleName":"","lastName":"Huo","suffix":""},{"id":614826567,"identity":"a75a74da-6ce7-474d-a43c-46891a259163","order_by":15,"name":"Wei Tang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2026-03-29 11:15:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9258298/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9258298/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106401782,"identity":"efe7fb2e-7853-49f7-882c-f71553044a06","added_by":"auto","created_at":"2026-04-08 09:09:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":999553,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flowchart\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9258298/v1/7e97a879ba128d6cae9e7386.png"},{"id":105985056,"identity":"44409c79-c705-4d88-a261-c9ddff90ea2c","added_by":"auto","created_at":"2026-04-02 07:20:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5511498,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProgression-free survival and overall survival of enrolled patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProgression-free survival (A) and overall survival (B) of enrolled patients. Progression-free survival (C) and overall survival (D) in T-cell lymphoma patients with different subtypes.\u003c/p\u003e\n\u003cp\u003eAbbreviations: nTFHL-AI, nodal T-follicular helper cell lymphoma, angioimmunoblastic-type; PTCL-NOS, peripheral T-cell lymphoma-not otherwise specified; ALCL, anaplastic large-cell lymphoma.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9258298/v1/f2f7c36204174ba5d4c4575d.png"},{"id":106405502,"identity":"90bc5650-e914-42f0-8c0c-1b099c3216b5","added_by":"auto","created_at":"2026-04-08 09:26:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5715379,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9258298/v1/e7559305-4fa6-4cc9-abfb-054614e51daa.pdf"},{"id":106093345,"identity":"2252c69e-eaf5-44c6-b9d1-28802ea32c0b","added_by":"auto","created_at":"2026-04-03 11:36:55","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16760,"visible":true,"origin":"","legend":"Tables","description":"","filename":"ChidamideTables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-9258298/v1/2208377c2297ae71556fa447.xlsx"},{"id":105985057,"identity":"03934bb4-d78b-4616-80d7-5de38fd6424b","added_by":"auto","created_at":"2026-04-02 07:20:09","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":103763,"visible":true,"origin":"","legend":"Study Protocol","description":"","filename":"StudyProtocol.docx","url":"https://assets-eu.researchsquare.com/files/rs-9258298/v1/6aac46e3866aae4a0ee03fe6.docx"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Chidamide-BEAM Conditioning plus Autologous Stem Cell Transplantation for T-cell Lymphoma: A Single-Arm, Single-Center, Phase 2 Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eT-cell lymphoma (TCL) represents a rare and heterogeneous subset of non-Hodgkin\u0026rsquo;s lymphomas (NHL), accounting for approximately 5\u0026ndash;10% of NHL cases in Western countries and 15\u0026ndash;20% in Asia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. There are many pathological types of TCL, including nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI), peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), and anaplastic large-cell lymphoma (ALCL) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The intrinsic diversity and rarity of TCL complicates the diagnostic process, necessitating a comprehensive judgment according to multiple examination results, such as pathological examination, immunohistochemistry, gene rearrangement, and imaging examination [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe current treatment efficacy of TCL is unsatisfactory due to the lack of targeted treatment strategies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. First-line TCL treatment is still mainly as the CHOP regimen, following the treatment framework for B-cell NHL, with poor clinical outcomes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Recent advances in molecular pathogenesis and genomic profiling have stimulated the discovery and clinical application of molecular biomarkers in TCL subtypes, enabling personalized care for TCL patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Epigenetic modifiers, including histone deacetylation (HDAC) inhibitors and hypomethylating agents, in the relapsed setting and in combination with chemotherapy in the front-line setting, have been demonstrated to improve the clinical efficacy of TCL treatment [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. HDAC inhibitors activate the acetylation of histones, change the chromatin structure, modulate the accessibility of transcription factors to their target, promote the expression of tumor-suppressor genes, and induce anti-tumor activity [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Chidamide is a selective inhibitor of HDAC1, 2, 3, and 10 and could improve treatment efficacy in relapsed/refractory TCL [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAutologous stem cell transplantation (ASCT) is a therapeutic strategy for TCL patients in the first remission. The 2-year progression-free survival (PFS) rate with CHOP-based induction followed by ASCT was 52.9% in a prospective study [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Despite progress in molecular subtyping and therapeutic effect [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], prognosis of TCL patients requires further improvement in the era of ASCT [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Since BEAM (carmustine, etoposide, cytarabine, and melphalan) is the standard conditioning regimen for ASCT [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], optimizing the pretreatment plan and maintenance approach is crucial for enhancing the efficacy of TCL management. Given the therapeutic effect of chidamide in TCL [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], adding chidamide to the ASCT pretreatment and maintenance regimen may improve clinical efficacy. Therefore, this study was conducted to evaluate the effect and safety of the chidamide-BEAM (Chi-BEAM) regimen followed by front-line ASCT and chidamide maintenance in TCL patients.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e \u003cp\u003eThis single-arm, single-center, phase 2 trial (NCT05367856) was conducted at Ruijin Hospital in China, from June 15, 2022, and June 15, 2023. Eligible patients were aged 18\u0026ndash;65 years and histologically diagnosed as TCL, excluding IPI 0\u0026ndash;1 ALK+ anaplastic lymphoma, with complete remission (CR) or partial remission (PR) after first-line chemotherapy. Furthermore, eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, no serious organic lesions in the main organs, and met the requirements of the following laboratory examination indicators (conducted within 7 days before treatment): 1. white blood cell count\u0026thinsp;\u0026ge;\u0026thinsp;3.0 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, absolute neutrophil count\u0026thinsp;\u0026ge;\u0026thinsp;1.5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, hemoglobin\u0026thinsp;\u0026ge;\u0026thinsp;90g/L, platelets\u0026thinsp;\u0026ge;\u0026thinsp;75 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L; 2. total bilirubin\u0026thinsp;\u0026le;\u0026thinsp;1.5 \u0026times; the upper limit of normal (ULN); 3. aspartate transaminase (AST) and alanine transaminase (ALT)\u0026thinsp;\u0026le;\u0026thinsp;2.5\u0026times; the ULN; and 4. normal creatinine clearance rate. Furthermore, eligible patients had no prior history of malignancy, no heart dysfunction, and a life expectancy of at least 3 months. Participants were required to provide written informed consent before the study.\u003c/p\u003e \u003cp\u003ePatients were excluded if they had previous bone marrow transplantation; other malignant tumors within the past five years; or uncontrollable cardiocerebrovascular, coagulative, autoimmune, or serious infectious disease. Those who were HBsAg, HCV, or HIV positive were also excluded. HBV and HCV serological positivity were allowed; however, DNA/RNA testing was required to be negative. Those with a left ventricular ejection fraction (LVEF) of 50% or less, mental illness, or who were suspected to be unable to fully comply with the study protocol were also excluded, as were pregnant or lactating women and patients with an uncontrollable medical condition that researchers believed would affect their participation in the study. Treatment response was assessed according to standardized criteria for non-Hodgkin lymphoma.\u003c/p\u003e \u003cp\u003e This study was conducted according to the principles of the Declaration of Helsinki. The final version of the protocol was reviewed and approved by an independent ethics committee. All patients gave written informed consent. This study is registered with ClinicalTrials.gov (NCT05367856) and is closed to new participants.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eAll patients received Chi-BEAM followed by ASCT. The regimens comprised 30 mg chidamide administered orally on D-7, D-4, D-1, and D\u0026thinsp;+\u0026thinsp;3, 300 mg/m\u003csup\u003e2\u003c/sup\u003e carmustine administered intravenously on D-7, 100 mg/m\u003csup\u003e2\u003c/sup\u003e etoposide administered intravenously every 12 hours on D-6-D-3, 200 mg/m\u003csup\u003e2\u003c/sup\u003e/d cytarabine administered intravenously every 12 hours on D-6-D-3, and 140 mg/m\u003csup\u003e2\u003c/sup\u003e melphalan administered intravenously on D-2. The day of stem cell reinfusion was designated D0. Granulocyte-colony stimulating factor was administered if the absolute neutrophil count was less than 0.5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e cells/L after hematopoietic stem cell transfusion. Platelet transfusions were permitted at the discretion of the investigator when the platelet count was less than 20 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e cells/L. Supportive medications and other blood product transfusions were provided according to local protocols.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was 2-year PFS rate, defined as the proportion of patients who were alive and free from disease progression at 2 years after randomization. The secondary endpoints included 2-year overall survival (OS) rate (the proportion of patients who were alive at 2 years after randomization), CR rate (the percentage of participants with complete response was determined using the 2014 Lugano criteria), the time of hematopoietic reconstruction, and transplantation-related adverse events. The first day of neutrophil counts\u0026thinsp;\u0026ge;\u0026thinsp;0.5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L for 3 consecutive days was the time of successful implantation of granulocytes. The first day of platelet counts\u0026thinsp;\u0026ge;\u0026thinsp;20.0 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L for 7 consecutive days without platelet infusion was considered the successful megakaryocyte implantation time.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAs reported previously [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], the 2-year PFS rate for TCL patients was conservatively set at 52.9%. Chi-BEAM pretreatment was expected to increase the 2-year PFS rate to 81% after ASCT. To achieve 90% power at a one-sided 0.025 significance, we required an overall sample size of 23 patients, assuming a dropout rate of 8%, according to PASS software calculations. The study duration was determined to be 3 years, with patients\u0026rsquo; accrual occurring within the first 2 years. PFS was defined as the time from the date of transplantation to the date of disease progression, relapse, or death from any cause, whichever occurred first. OS was defined as the time from the date of transplantation to the date of death from any cause. Patients who were lost to follow-up or who had not experienced an event by the end of the study period were censored at the time of their last known follow-up. Survival curves were estimated using the Kaplan-Meier method, and comparisons between groups were performed with the log-rank test. All statistical analyses were performed using IBM SPSS Statistics, Version 26.0, and a two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eParticipant Characteristics\u003c/h2\u003e \u003cp\u003eBetween June 15, 2022, and June 15, 2023, a total of 26 patients were screened for eligibility, of whom 2 withdrew consent and 1 experienced mobilization failure. Consequently, 23 patients were enrolled and proceeded to transplantation. A flow chart of the study is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The intention-to-treat population (ITTP) of 23 patients included: PTCL-NOS (n\u0026thinsp;=\u0026thinsp;6; 26.1%), ALK-negative ALCL (n\u0026thinsp;=\u0026thinsp;6; 26.1%), and nTFHL-AI (n\u0026thinsp;=\u0026thinsp;11; 47.8%); 56.5% of the patients were men, and the median age was 49 years (range, 22 to 65 years). Regarding disease characteristics, 95.7% of the patients presented with advanced stage disease, 87.0% with elevated serum lactate dehydrogenase, and 47.8% with B symptoms. The baseline clinical and pathological characteristics are summarized in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurvival\u003c/h3\u003e\n\u003cp\u003eAt the time of analysis, all 23 enrolled patients were alive. The median follow-up of surviving patients was 24.6 months (range, 18.2 to 38.7 months). In the ITTP, the 2-year PFS and OS rates were 95.7% (95% CI, 72.9\u0026ndash;99.4) and 100.0% (95% CI, 100.0-100.0), respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-B). When analyzed by pathological subtyping, the 2-year PFS rates were 100% in ALCL, 100% in PTCL-NOS, and 88.9% in nTFHL-AI, with a 2-year OS of 100% across all these subtypes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC-D).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eRemission rates\u003c/h3\u003e\n\u003cp\u003eAt 3 months post-transplantation, 17 (73.9%) patients had achieved CR and 5 (21.7%) had achieved PR. Subsequently, one patient (4.3%) experienced relapse or disease progression within the initial two-year period, or more precisely, at 4.4 months post-transplantation. Clonality analysis conducted at the time of relapse confirmed the same malignant clone as identified at initial diagnosis. This case, characterized by high-risk mutations in \u003cem\u003eTET2\u003c/em\u003e, \u003cem\u003eRHOA\u003c/em\u003e, and \u003cem\u003eIDH2\u003c/em\u003e and classified as the T1 subtype [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], likely contributed to the poor response to transplantation. No transplant-related mortality was reported until the last follow-up.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eHematopoietic reconstitution\u003c/h2\u003e \u003cp\u003eThe median time for neutrophil engraftment was 10 days, and for megakaryocytic engraftment was 16 days. The post-transplant period was characterized by significant cytopenias, with a high incidence of febrile agranulocytosis (82.6%, 19/23), which had a median duration of 4 days; the median duration of severe (Grade 4) agranulocytosis and athrombocytopenia was 8 and 10 days, respectively. Supportive care requirements were notable for platelet transfusions (median 4 units), while red blood cell transfusions were minimal (median 0.5 units), consistent with the low incidence of severe anemia (13%, 3/23, Table\u0026nbsp;2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eTransplantation-related Adverse Events\u003c/h2\u003e \u003cp\u003eGrades 3 to 4 hematologic toxicities were seen in 100% of patients, whereas grades 3 to 4 non-hematologic toxicities were recorded in 4 patients (17.4%), with infectious complications as the most frequent adverse event (n\u0026thinsp;=\u0026thinsp;3; 13.0%), followed by hepatic (n\u0026thinsp;=\u0026thinsp;2; 8.7%), vomiting (n\u0026thinsp;=\u0026thinsp;1; 4.3%), and mucositis (n\u0026thinsp;=\u0026thinsp;1; 4.3%). No patients died due to adverse events (Table\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eASCT is an important consolidation strategy for TCL in first remission and has been shown to enhance therapeutic efficacy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The recommendation for ASCT is based on the findings of several prospective and retrospective studies. The largest prospective study, Nordic Lymphoma Group (NLG)-T-01, revealed that dose-dense induction followed by ASCT is well tolerated and results in better outcomes for transplantation-eligible patients with PTCL (Table\u0026nbsp;4) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Similarly, a multi-center retrospective analysis by the GELTAMO/FIL group reported significantly improved 5-year PFS and OS in patients undergoing upfront ASCT compared with those who did not, reinforcing the role of ASCT as consolidation therapy in PTCL (Table\u0026nbsp;5) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Therefore, ASCT is consolidated as a standard of care for TCL in the first remission. The BEAM regimen remains the most widely used conditioning regimen before ASCT in TCL patients. However, optimizing this conditioning strategy is essential to further enhance treatment efficacy, particularly given the substantial proportion of patients who still experience disease relapse post-ASCT [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChidamide, an orally available HDAC inhibitor selectively targeting HDAC1, 2, 3, and 10, has been approved in China both as monotherapy and in combination regimens for TCL [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Preclinical and clinical studies have shown that chidamide exerts anti-tumor effects through multiple mechanisms, including inhibition of cell proliferation, induction of G0/G1 cell cycle arrest [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], promotion of apoptosis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and sensitization to chemotherapy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] across various hematologic malignancies. For instance, chidamide can enhance the cytotoxicity of cytarabine in CD34\u0026thinsp;+\u0026thinsp;acute myeloid leukemia cells by suppressing proliferation, increasing apoptosis, and reinforcing cell cycle arrest in vitro [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Clinically, combinations such as chidamide with etoposide, prednisone, and thalidomide have improved PFS and OS in previously untreated nTFHL-AI patients [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. These findings provide a strong rationale for integrating chidamide with chemotherapeutic agents.\u003c/p\u003e \u003cp\u003eGiven the established efficacy of chidamide in TCL, its incorporation into the ASCT conditioning regimen represents a rational approach to improve transplant outcomes. The exploration of novel chidamide-containing conditioning regimens has yielded promising outcomes in patients undergoing ASCT. For high-risk, relapsed/refractory lymphoma, the Chi-CGB regimen achieved PFS of 80.6% and OS of 86.1% [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Similarly, the Chi-BEAC regimen demonstrated comparable efficacy, with 2-year PFS and OS as 81.1% and 86.1% OS, respectively [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. However, no study to date has systematically optimized the classic BEAM backbone with chidamide. Our findings directly address this unmet need. In our cohort of 23 transplantation-eligible TCL patients, the Chi-BEAM regimen yielded outstanding outcomes: at a median follow-up of 24.6 months, the 2-year PFS and OS were 95.7% and 100.0%, respectively. Notably, this promising efficacy was consistently observed across key pathological subtypes, including ALCL, PTCL-NOS, and nTFHL-AI. When compared with historical data using standard BEAM (Table\u0026nbsp;4), the Chi-BEAM regimen appears to confer a substantial survival advantage, providing the first clinical evidence that addition of chidamide into the established BEAM backbone is not only feasible but also lead to superior transplant outcomes.\u003c/p\u003e \u003cp\u003eOur study has limitations. The single-arm design and small sample size prevent definitive conclusions regarding the magnitude of benefit attributable to chidamide, taking account that TCL is a rare entity of NHL. Potential toxicities from combining chidamide with intensive chemotherapy require further monitoring, and longer follow-up is needed to assess long-term survival and late relapse.\u003c/p\u003e \u003cp\u003eIn conclusion, the Chi-BEAM regimen represents a promising and rationally designed conditioning strategy that demonstrates remarkable efficacy and a manageable safety profile. It is worthy of rigorous clinical evaluation in larger, randomized controlled trials involving transplantation-eligible TCL patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patients and their families, as well as the participating study teams, for making this study possible. This work was partially supported by research funding from the National Key R\u0026amp;D Program of China (2022YFC2502600 and 2023YFC3605704), the National Natural Science Foundation of China (82470173, 82200201, 82130004, 82170178 and 82070204), the Chang Jiang Scholars Program, Shanghai Lymphoma Clinical Cohort of Shanghai Hospital Development Center (SHDC2025CCS008), the Multicenter Hematology-Oncology Program Evaluation System (M-HOPES), the Shanghai Sailing Program (23YF1423700), Collaborative Innovation Center of Systems Biomedicine, Hainan Provincial Natural Science Foundation (2026-387), Hainan Provincial Joint Project for Health and Health Technology Innovation (2026-71), Medical Engineering Cross Project of Shanghai Jiaotong University.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMMJ conceived, designed, directed and supervised the study and wrote the manuscript. YGS wrote the protocol, collected and analyzed clinical data, and wrote the manuscript. SYC, and HYL collected and analyzed clinical data. RJM was responsible for the statistical review. LW, SC, PPX, ZZ, LDZ, HJZ, MCC, YHH, DF, YJ H, WT recruited patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eDeclaration of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eData sharing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll sequencing data (including Whole Exome Sequencing) have been deposited in the GSA-Human database and can be accessed through the following link: https://bigd.big.ac.cn/gsa-human/browse/HRA004246. It is available by contacting the lead contact, Meng-Meng Ji ([email protected]), upon request.\u003cstrong\u003e\u003cbr clear=\"all\"\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMulvey E, Ruan J. Biomarker-driven management strategies for peripheral T cell lymphoma. J Hematol Oncol. 2020;13:59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShea L, Mehta-Shah N. Peripheral T-cell lymphoma: are all patients high risk? Blood. 2024;144:2604\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchi E, O'Connor OA. The rapidly changing landscape in mature T-cell lymphoma (MTCL) biology and management. CA Cancer J Clin. 2020;70:47\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa H, Marchi E, O'Connor OA. The peripheral T-cell lymphomas: an unusual path to cure. Lancet Haematol. 2020;7:e765-e71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang Z, Fu Y, Yang H, Zhou Y, Shi M, Li Q, et al. Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application. Mol Cancer. 2024;23:36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuan Y, Li X, Luan Y, Luo J, Dong Q, Ye S, et al. Therapeutic challenges in peripheral T-cell lymphoma. Mol Cancer. 2024;23:2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang P, Wang Z, Liu J. Role of HDACs in normal and malignant hematopoiesis. Mol Cancer. 2020;19:5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi MQ, Xu Y, Fu X, Pan DS, Lu XP, Xiao Y, et al. Advances in targeting histone deacetylase for treatment of solid tumors. J Hematol Oncol. 2024;17:37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIzykowska K, Rassek K, Korsak D, Przybylski GK. Novel targeted therapies of T cell lymphomas. J Hematol Oncol. 2020;13:176.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ed'Amore F, Relander T, Lauritzsen GF, Jantunen E, Hagberg H, Anderson H, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30:3093\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang YH, Qiu YR, Zhang QL, Cai MC, Yu H, Zhang JM, et al. Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes. Cell Rep Med. 2024;5:101416.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrink M, Meeuwes FO, van der Poel MWM, Kersten MJ, Wondergem M, Mutsaers P, et al. Impact of etoposide and ASCT on survival among patients aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years with stage II to IV PTCL: a population-based cohort study. Blood. 2022;140:1009\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu J, Yu D, Han X, Zhu L, Huang Z. Comparison of Allogeneic Stem Cell Transplant and Autologous Stem Cell Transplant in Refractory or Relapsed Peripheral T-Cell Lymphoma: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4:e219807.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia-Sancho AM, Bellei M, Lopez-Parra M, Gritti G, Cortes M, Novelli S, et al. Autologous stem-cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: a multicenter GELTAMO/FIL study. Haematologica. 2022;107:2675\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Y, Jia B, Xu W, Li W, Liu T, Liu P, et al. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol. 2017;10:69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePang Z, Wang Y, Liu Z, Zhang S, Wei C, Xu Z, et al. Linperlisib Plus Chidamide in Relapsed or Refractory Cutaneous T-Cell Lymphoma: A Nonrandomized Clinical Trial. JAMA Dermatol. 2025;161:923\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAtallah-Yunes SA, Wang Y. Dual epigenetic therapy plus chemotherapy in peripheral T cell lymphoma with T follicular helper phenotype. Med. 2024;5:1335\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing K, Liu H, Yang H, Zhu H, Ma J, Peng H, et al. A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma. Med. 2024;5:1393\u0026thinsp;\u0026ndash;\u0026thinsp;401 e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu S, Hou Y, Dovat K, Dovat S, Song C, Ge Z. Synergistic effect of HDAC inhibitor Chidamide with Cladribine on cell cycle arrest and apoptosis by targeting HDAC2/c-Myc/RCC1 axis in acute myeloid leukemia. Exp Hematol Oncol. 2023;12:23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Liu YC, Zhu CY, Yan F, Wang MZ, Chen XS, et al. Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway. J Exp Clin Cancer Res. 2020;39:278.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao H, Jiang Y, Lin F, Zhong M, Tan J, Zhou Y, et al. Chidamide and apatinib are therapeutically synergistic in acute myeloid leukemia stem and progenitor cells. Exp Hematol Oncol. 2022;11:29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Wang Y, Zhou Y, Li J, Chen K, Zhang L, et al. Cooperative effect of chidamide and chemotherapeutic drugs induce apoptosis by DNA damage accumulation and repair defects in acute myeloid leukemia stem and progenitor cells. Clin Epigenetics. 2017;9:83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Zhang M, Song W, Cai Q, Zhang L, Sun X, et al. Chidamide plus prednisone, etoposide, and thalidomide for untreated angioimmunoblastic T-cell lymphoma in a Chinese population: A multicenter phase II trial. Am J Hematol. 2022;97:623\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJi J, Liu Z, Kuang P, Dong T, Chen X, Li J, et al. A new conditioning regimen with chidamide, cladribine, gemcitabine and busulfan significantly improve the outcome of high-risk or relapsed/refractory non-Hodgkin's lymphomas. Int J Cancer. 2021;149:2075\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXia Y, Wang L, Ding K, Wu J, Yin H, Hu M, et al. Chidamide-BEAC plus autologous stem cell transplantation in high-risk non-Hodgkin lymphoma: a phase II clinical trial. Chin Med J (Engl). 2023;136:1491\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9258298/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9258298/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis clinical trial (NCT05367856) evaluated the Chi-BEAM conditioning regimen followed by frontline autologous stem cell transplantation (ASCT) and chidamide maintenance in T-cell lymphoma (TCL). This study screened and enrolled 23 TCL patients between June 15, 2022, and June 15, 2023. Eligible participants were aged 18\u0026ndash;65 years, had histological diagnosis of TCL (excluding ALK-positive anaplastic large cell lymphoma with International Prognostic Index [IPI] score 0\u0026ndash;1), and achieved complete remission (CR) or partial remission (PR) after first-line chemotherapy. All enrolled patients received Chi-BEAM followed by ASCT and chidamide maintenance for 2 years, initiated after hematopoietic recovery. The primary endpoint was 2-year progression-free survival (PFS) rate. Secondary endpoints were 2-year overall survival (OS) rate, CR rate, time to hematopoietic reconstruction, and transplantation-related adverse events. At analysis, all 23 patients were alive. Median follow-up was 24.6 months (range, 18.2\u0026ndash;38.7 months). The 2-year PFS and OS rates were 95.7% (95% CI, 72.9%-99.4%) and 100.0% (95% CI, 100.0%-100.0%), respectively. Grade 3\u0026ndash;4 non-hematological adverse events included infection (13.0%), hepatic toxicity (8.7%), vomiting (4.3%), and mucositis (4.3%). The Chi-BEAM regimen with frontline ASCT followed by chidamide maintenance represents a potentially effective and well-tolerated treatment strategy for TCL, showing promising survival outcomes and a manageable safety profile.\u003c/p\u003e","manuscriptTitle":"Chidamide-BEAM Conditioning plus Autologous Stem Cell Transplantation for T-cell Lymphoma: A Single-Arm, Single-Center, Phase 2 Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:20:05","doi":"10.21203/rs.3.rs-9258298/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2026-04-24T13:25:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-04-17T10:11:57+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-03-30T19:37:51+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-03-30T19:28:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-30T15:03:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-29T11:13:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bone Marrow Transplantation","date":"2026-03-29T11:13:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0772c77f-aedb-4230-a5a2-a891c4930c30","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":65421081,"name":"Biological sciences/Cancer/Cancer therapy/Targeted therapies"},{"id":65421082,"name":"Biological sciences/Cancer/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/T-cell lymphoma"}],"tags":[],"updatedAt":"2026-04-24T13:30:52+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:20:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9258298","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9258298","identity":"rs-9258298","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}