造血干细胞移植治疗慢性髓系白血病的疗效分析

背景与目的：慢性髓系白血病(chronic myelogenous leukemia,CML)是一种常见的恶性血液疾病,造血干细胞移植(hematopoietic stem cells transplantation,HSCT)是治疗CML最主要的手段。本研究评价自体(auto-)或异体(allo-)HSCT治疗CML的临床疗效。方法：44例CML息者接受HSCT治疗,其中8例采用净化auto-HSCT,30例采用相关allo—HSCT,6例采用无关allo-HSCT;预处理方案：31例接受TBI CY(全身放疗 环磷酰胺)方案,12例采用改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案,1例采用MACC(马法兰、阿糖胞苷、环磷酰胺、环已亚硝脲)方案;移植物抗宿主病(GVHD)预防：相关移植采用CsA MTX(环孢素A 甲氨蝶呤)方案,无关移植采用CsA MTX MMF(霉酚酸酯) ATG(抗胸腺细胞球蛋白)方案。此外,移植前加速期和急变期患者单用CsA。Kaplan—Meier生存模型评估移植后无病生存。结果：8例接受激活骨髓(ABM)联合反义寡核苷酸或联合STI571体内外净化auto-HSCT后,除1例死于移植中相关并发症外,其余均获得部分或完全细胞或分子遗传学缓解,其中1例急变期患者血液学完全缓解(CR)后移植获分子遗传学CR达81个月。36例allo—HSCT患者除1例死于肝静脉闭塞综合征(hepatic veno-occlusive disease,VOD)和1例移植前急变患者移植后无效以外,其余患者均获CR。移植中感染发生率为38．6％,VOD发生率为9．1％,出血性膀胱炎(hemorrhagic cystitis,HC)发生率为15．9％,巨细胞病毒(CMV)性肺炎为11．4％,VOD、HC和CMV肺炎均发生在allo-HSCT患者。急性GVHD发生率在相关与无关移植中分别为40．0％与33．3％。在相关移植中慢性GVHD发生率为43．4％。移植相关死亡率在自体与异体HSCT中分别为12．5％与16．7％,auto—HSCT复发率为37．5％,相关allo-HSCT复发率为13．3％。移植后5年无病生存率在自体与相关异体移植中分别为18．7％与53．7％。移植前慢性期与加速期和急变期患者相关allo-HSCT后5年无病生存率分别为66．4％与26．7％。结论：allo—HSCT对CML患者,尤其是慢性期患者具有较高的临床治愈率;CsA MTX MMF ATG四联方案在无关allo-HSCT中应用能降低移植后急性GVHD的发生率及程度;采用净化骨髓自体移植能延长CML患者生存期,甚至少部分患者可获得临床治愈。

Hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia

BACKGROUND & OBJECTIVE: Chronic myelogenous leukemia (CML) is a malignant hematological disease.CML patients are commonly treated with hematopoietic stem cells transplantation (HSCT). This study was designed to evaluate the effect of HSCT on the patients with CML. METHODS: Forty-four patients with CML were treated by HSCT, including 8 cases treated with purging autologous transplantation, 30 cases with related donor allogeneic HSCT (allo-HSCT), and 6 cases with unrelated donor allo-HSCT. The conditioning regimen was TBI (total-body irradiation)+CY (CTX) protocol in 31 patients and modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocal in 12 patients, and MACC (Melphalan, Ara-C, CTX and CCNU) protocol in one patient. CsA (cyclosporine) and MTX were used in the patients with related donor allo-HSCT, and CsA and MTX added to mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) were used in the patients with unrelated donor all-HSCT for graft versus host disease (GVHD) prophylaxis. Otherwise, CsA was only used in the patients with accelerated phase(AP) and blast crisis(BC) for GVHD prophylaxis. Kaplan-Meier survival analysis model was used to estimate the overall survival (OS) and the disease-free survival (DSF) at 5 years after transplantation. RESULTS: Eight patients with autologous transplantation, except one case died of transplantation-related-complication, obtained part or complete cytogenetic remission within 3 months after transplantation. One patient, who was BC and obtained complete remission (CR) in hematology before transplantation,obtained complete molecular remission for 81 months after autologous transplantation. All patients obtained CR, except one patient died of hepatic veno-occlusive disease (VOD) and one case did not obtained CR, in 36 patients with allo-HSCT after transplantation. The incidence of infection and VOD during transplantation were 38.6% and 9.1%, respectively. The incidences of hemorrhagic cystitis (HC) and cytomegalovirus (CMV) pneumonia after transplantation were 15.9% and 11.4%, respectively. VOD, HC, and CMV pneumonia did not occur in the patients with autologous transplantation. The incidence of acute GVHD in the patients with related and unrelated donor transplantation were 40.0% and 33.3%, respectively. The incidence of chronic GVHD was 43.4% in the patients with related donor transplantation. The rates of transplant-related mortality (TRM) in the patients with autologous and allogeneic transplantation were 12.5% and 16.7%, respectively. The rates of relapse in patients with autologous and related donor transplantation were 37.5% and 13.3%, respectively. The DFSs at 5 years in patients with autologous and related donor transplantation after transplantation were 18.7% and 53.7%, respectively. The DFS at 5 years in patients with CP (chronic phase) or AP and BC before transplantation were 66.4% and 26.7%, respectively. CONCLUSION: all-HSCT shows higher clinical cure rate to CML patients with CP. CsA+MTX+MMF+ATG protocol is more effective for acute GVHD prophylaxis and can decrease the incidence and severity of acute GVHD in patients with unrelated donor transplantation. Autologous transplantation with bone marrow purged can prolong the survival time and a few patients may be cured with autologous transplantation in CML.