Abstract: 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.