Chidamide combined with a modified Bu-Cy conditioning regimen improves survival in patients with T-cell acute lymphoblastic leukemia/lymphoma undergoing allogeneic hematopoietic stem cell transplantation

• Published in: Annals of hematology Vol. 103; no. 8; pp. 3083 - 3093
• Main Authors: Cao, Xuanqi, Li, Zheng, Zhang, Yanming, Cui, Qingya, Dai, Haiping, Ma, Yunju, Li, Mengyun, Chen, Sifan, Yin, Jia, Cui, Wei, Chen, Jia, Sun, Aining, Qiu, Huiying, Chen, Suning, Zhu, Xiaming, Andersson, Borje S., Wu, Depei, Tang, Xiaowen
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2024; Springer Nature B.V
• Subjects: Adolescent; Adult; Allografts; Aminopyridines - administration & dosage; Aminopyridines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides - administration & dosage; Benzamides - therapeutic use; Busulfan - administration & dosage; Busulfan - therapeutic use; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Disease-Free Survival; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Hematology; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphoma; Male; Medicine; Medicine & Public Health; Middle Aged; Mortality; Oncology; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Retrospective Studies; Stem cell transplantation; Survival Rate; Transplantation Conditioning - methods; Transplantation, Homologous; Young Adult; Conditioning regimen; T acute lymphoblastic leukemia/Lymphoma; Histone deacetylase inhibitors; Allogeneic stem cell transplantation
• ISSN: 0939-5555; 1432-0584; 1432-0584
• DOI: 10.1007/s00277-024-05849-y

This study aimed to evaluate the efficacy and safety of chidamide (Chi) combined with a modified Busulfan-Cyclophosphamide (mBuCy) conditioning regimen for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only in the same period. The leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse-related mortality (NRM) were evaluated. Patients in the Chi group were associated with lower 2-year CIR (19.0 vs. 41.4%, P  = 0.030), better 2-year LFS (76.1 vs. 48.1%, P  = 0.014), and had no significant difference in 2-year OS (80.5 vs. 66.4%, P  = 0.088). Patients with minimal residual disease (MRD) positive before HSCT in the Chi group exhibited an advantage in 2-year LFS and a trend towards better 2-year OS (75.0 vs. 10.2%, P  = 0.048; 75.0 vs. 11.4%, P  = 0.060, respectively). Multivariable analysis showed that the chidamide intensified regimen was independently associated with better LFS (HR 0.23; 95%CI, 0.08–0.63; P  = 0.004), and showed no significant impact with OS for all patients (HR 0.34, 95%CI, 0.11–1.07; P  = 0.064). The cumulative incidence rates of grade II-IV aGVHD were similar (36.4 vs. 38.6%, P  = 0.858). 20 patients in Chi group evinced an elevation in γ-glutamyltransferase, as compared to the mBuCy group (90.9 vs. 65.9%, P  = 0.029). No transplantation-related mortality was documented within the first 100 days after transplantation. The results demonstrate that the chidamide intensified regimen may be an effective and acceptable safety option for T-ALL/LBL undergoing allo-HSCT, and further validation is needed.