TBI+rATG为基础的联合预处理方案单倍体造血干细胞移植治疗化疗耐药进展期外周T细胞淋巴瘤11例

Efficacy and safety of TBI+rATG-based conditioning regimen for haploidentical allogeneic hematopoietic stem cell transplantation in 11 cases of chemotherapy-resistant advanced peripheral T-cell lymphoma

目的评估以全身放射治疗(TBI)+兔抗人胸腺细胞免疫球蛋白(rATG)为基础预处理方案的单倍体造血干细胞移植(haplo-HSCT)治疗化疗耐药进展期外周T细胞淋巴瘤(PTCL)的疗效与安全性。方法纳入2019年9月至2022年12月在上海力泉医院和上海闸新中西医结合医院血液科接受TBI+rATG为基础预处理方案haplo-HSCT的11例化疗耐药进展期PTCL患者,对其临床资料进行回顾性分析。结果①11例患者中男6例,女5例,中位年龄40(22~58)岁;外周T细胞淋巴瘤(非特指型)6例,血管免疫母细胞性T细胞淋巴瘤3例,蕈样真菌病(大细胞转化)1例,T大颗粒淋巴细胞白血病1例;Lugano分期均为Ⅲ、Ⅳ期;8例患者有B症状;移植前中位化疗线程数为4(2~10)线,移植前疾病状态均为疾病进展(PD)。诊断至移植的中位时间为17(6~36)个月。②预处理方案:TBI总量10 Gy;rATG 2.5 mg·kg^(-1)·d^(-1)、-5 d~-2 d;依托泊苷15 mg·kg^(-1)·d^(-1),-5 d、-4 d,环磷酰胺50 mg·kg^(-1)·d^(-1),-3 d、-2 d。原发病中枢神经系统侵犯的患者,将依托泊苷和环磷酰胺替换为塞替派(5 mg·kg^(-1)·d^(-1),-5 d、-4 d)并加用阿糖胞苷(2.0 g/m2每日2次,-3 d、-2 d)。③所有患者均成功植入,中位中性粒细胞植入时间为14.5(11~16)d,中位血小板植入时间为13(8~18)d。1例患者发生Ⅰ~Ⅱ度急性移植物抗宿主病(GVHD),1例患者发生Ⅲ/Ⅳ度急性GVHD,8例存活患者中4例发生慢性GVHD。④移植后有9例患者获得完全缓解(CR)。⑤所有患者预处理后发生造血抑制,3例出现腹泻,4例发生黏膜炎,3例转氨酶/胆红素升高,7例发生感染,经过治疗均得到缓解。⑥移植后1年非复发死亡率(NRM)为(22.5±14.0)%,累积复发率(CIR)为(20.2±12.7)%,总生存(OS)率为(72.7±13.4)%,无病生存(DFS)率为(63.6±14.5)%。结论 TBI+rATG为基础预处理haplo-HSCT是化疗耐药进展期PTCL有效且安全的治疗方法。

Objective To evaluate the clinical outcomes and safety of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)using a conditioning regimen based on total body irradiation(TBI)and rabbit anti-human thymocyte globulin(rATG)in the management of chemotherapy-resistant advanced peripheral T-cell lymphoma(PTCL).Methods Clinical data of 11 patients with chemotherapy-resistant advanced PTCL who underwent haplo-HSCT with a TBI+rATG-based conditioning regimen at the Department of Hematology,Shanghai Liquan Hospital and Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital,from September 2019 to December 2022 were retrospectively analyzed.Results①Among the 11 patients(six males and five females),with a median age of 40 years(range:22-58 years),there were six cases of PTCL,not otherwise specified(PTCL-NOS),three cases of angioimmunoblastic T-cell lymphoma(AITL),one case of large-cell transformation of mycosis fungoides(MF-LCT),and one case of T-cell large granular lymphocytic leukemia(T-LGLL).According to the Lugano staging system,all patients were in stageⅢorⅣ,and eight patients had B symptoms.Before transplantation,the median number of prior lines of chemotherapy was 4(range:2-10),and all patients had progressive disease(PD).The median time from diagnosis to transplantation was 17 months(range:6-36 months).②The conditioning regimen consisted of a TBI dose of 10 Gy,administered at 2 Gy on day-8 and 4 Gy from day-7 to day-6,rATG was administered at a daily dose of 2.5 mg/kg from day-5 to day-2.Etoposide(VP-16)was given at a dose of 15 mg/kg/d from day-5 to day-4,while cyclophosphamide(CTX)was administered at a dose of 50 mg/kg/d from day-3 to day-2.In patients with central nervous system involvement,etoposide and cyclophosphamide were replaced with thiotepa(TT)at a dose of 5 mg/kg/d from day-5 to day-4.Additionally,cytarabine(Ara-C)was added at a dose of 2.0 g/m^(2) twice a day from day-3 to day-2 into the conditioning.③Successful engraftment was achieved in all patients,with a median time to neutrophil engraftment of 14.5 d(range:11-16 d)and a median time to platelet engraftment of 13 days(range:8-18 days).Acute graft-versus-host disease(aGVHD)occurred in one patient(gradeⅠ-Ⅱ),and another patient experienced gradeⅢ-ⅣaGVHD.Among the eight survivors,four developed chronic GVHD(cGVHD).④Post-transplantation,nine patients achieved complete response(CR).⑤Hematopoietic suppression occurred in all patients after conditioning,with three experiencing diarrhea,four developing mucositis,three exhibiting elevated transaminase/bilirubin levels,and seven developing infectious complications.These non-hematologic adverse events were effectively managed.⑥At one year post-transplantation,the non-relapse mortality(NRM)was(22.5±14.0)%,the cumulative incidence of relapse(CIR)was(20.2±12.7)%,and overall survival(OS)rate was(72.7±13.4)%,and disease-free survival(DFS)rate was(63.6±14.5)%.Conclusion TBI+rATG-based conditioning regimen for haplo-HSCT is an effective and safe treatment approach for patients with chemotherapy-resistant advanced PTCL.