难治性白血病异基因造血干细胞移植超强预处理的疗效

目的 探讨异基因造血干细胞移植超强预处理联合移植后诱导移植物抗白血病(GVL)治疗难治未缓解白血病的预处理相关毒性(RRT)和疗效。方法 18例移植前难治未缓解白血病和62例移植前完全缓解的急性白血病或慢性粒细胞白血病慢性期病人分别接受超强预处理方案和全身放疗+环磷酰胺或改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案(对照组)。在难治性白血病移植后30d未出现移植物抗宿主病(GVHD)病人,采用早期快速递减环孢素A或供体淋巴细胞输注诱导GVL。统计移植后RRT发生率与致死率、移植后完全缓解率、GVHD发生率、白血病复发和无病生存率等。结果 移植后除超强预处理组1例和对照组2例死于移植相关并发症外,其余病人均获得造血重建。两组总RRT发生率均为100%,各脏器RRT发生均以胃肠最常见,超强预处理组和对照组分别为83.3%和85.5%,两组口腔RRT发生率分别为44.4%和62.9%,膀胱RRT发生率分别为16.7%和33.9%,各组比较未见差异。超强预处理组RRT致死率为0,对照组为5%,两组比较无差异(P=0.341)。18例接收超强预处理病人除1例死于移植中感染外,其余病人均获完全缓解。超强预处理组和对照组移植后急性GVHD发生率分别为11.8%和18.3%,移植后3年估计无病生存率分别为(61.2±12.3)%和(65.0±7.4)%(P=0.6311)。结论 连续序惯超强预处理方案能提高移植前未缓解的难治性白血病移植后完全缓解率和无病生存率,不增加移植中RRT发生率和致死率。

Effects of allogeneic hematopoietic stem cell transplantation with very-high-dose conditioning regimen for refractory leukemia

Objective To explore the regimen-related toxicity (RRT) and therapeutic effects of very-high-dose conditioning regimen combined with induction of graft-versus-leukemia (GVL) effects in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory leukemia with unattainable complete remission (CR) before transplantation.Methods Eighteen patients who failed to obtain CR before transplantation received very-high-dose conditioning regimen protocol (experimental group),and 62 patients with acute leukemia with CR or with chronic myeloid leukemia in the chronic phase before transplan- tation received total body irradiation plus cyclophosphamide (CTX) or modified BuCY (hydroxyurea,busulfan,Ara-C,CTX) protocol (control group). In patients with refractory leukemia who did not develop graft-versus-host disease (GVHD) 30 d after the transplantation,GVL was induced by rapid reduction of the dosage of cyclosporin A or by donor lymphocytic infusion. The incidence and mortality of RRT and the rates of CR,GVHD and leukemia relapse after transplantation were investigated. Kaplan-Meier survival analysis model was used to estimate the disease-free survival (DFS) rate at 3 years post-transplantation. Results Except for one patient in the experimental group and two in the control group who died of transplantation- related complications,all the other patients obtained hematopoietic reconstitution. The total incidence of RRT was 100% in both groups,involving most frequently the stomach and intestines at the rate as high as 83.3% in the experimental group and 85.5% in the control group. RRT involving the oral cavity occurred in 44.4% and 62.9%,and that involving the bladder in 16.7% and 33.9% of the cases in the experimental group and control group,respectively,all similar between the groups (P=0.823,0.172 and 0.244,respectively). The RRT mortality was 0 and 5% in the experimental and control groups,respectively (P=0.341). With the exception of one patient who died of infection,all the other patients treated with very-high-dose conditioning regimen obtained CR. The incidences of acute/chronic GVHD were 58.8%/92.6% and 40.0%/55.8%,respectively,in the experimental and control groups. The incidence of leukemia relapse was 11.8% and 18.3%,and DFS at 3 years after transplan- tation was (61.2±12.3)% and (65.0±7.4)% (P=0.6311) in the two groups,respectively.Conclusion Consecutive very-high- dose conditioning regimen combined with GVL induction after transplantation can increase the rate of CR and DFS,without increasing RRT incidence and mortality in allo-HSCT for the refractory leukemia with unattainable CR pre-transplantation.