Autologous HSCT Followed By Immunotherapy and Maintenance Chemotherapy Compared with Allogeneic HSCT for Intermediate-Risk Molecules/Cytogenetics Acute Myeloblastic Leukemia in First Complete Remission

Background Autologous hematopoietic stem cell transplantation (auto-HSCT) is an alternative choice for acute myeloblastic leukemia (AML) with intermediate-risk molecules / cytogenetics (IR). Its disadvantage is high relapse rate, compared with allogeneic HSCT (allo-HSCT). To reduce leukemia relapse, we introduced a strategy of auto-HSCT followed by immunotherapy and maintenance chemotherapy for IR AML.

Methods One hundred and seventy-six IR AML in first complete remission (CR1) undergoing HSCT between January 2001 and December 2010 at our single institute were enrolled in this study. The choice of auto-HSCT or HLA-matched sibling transplantation was based on the donor source and patients’ desire. The conditioning regimen included BuCY (busulfan 4 mg/kg/day P.O. or 3.2 mg/kg/day I.V. on days -7 to -4, and cyclophosphamide 60 mg/kg/day on days -3 and -2) and BuF (busulfan 4 mg/kg/day P.O. or 3.2 mg/kg/day I.V. on days -7 to -4, and fludarabine 30mg/m²/day on days −6 to −2). Cyclosporine A and methotrexate were administered for GVHD prophylaxis. For patients undergoing auto-HSCT, interleukin-2 (IL-2) was administered from day 0 at a dose of 3×10⁶ U/day (three times a day) subcutaneously for 3 weeks. One or more subsequent cycles were given after a 30-day interval for up to 6 cycles unless the patient developed ≥ grade 3 toxicity. Standard chemotherapy was administered from three months post-transplantation. One or more subsequent cycles were given after a 90-day interval for up to 3 cycles. Survival, leukemia relapse and quality of life were compared between auto-HSCT and allo-HSCT.

Results Of the 176 IR AML-CR1, 102 patients received auto-HSCT, and 74 received allo-HSCT. The 5-year overall survival (OS) and disease-free survival (DFS) post-transplantation were 73.8%±4.3% and 67.2%±4.7%, 69.1%±6.3% and 69.1%±6.3%, respectively, in auto-HSCT and allo-HSCT.There were no difference in OS and DFS between auto-HSCT and allo-HSCT (P=0.533, P=0.948). The 5-year cumulative incidence of leukemia relapse was 25.8%±4.6% and 13.5%±4.8%, respectively (P=0.171). The 5-year non-relapse mortality was 10.4%±3.1% and 19.9%±5.7%, respectively, in auto-HSCT and allo-HSCT (P=0.157). The performance status, measured using the Karnofsky performance score, was observed in 85 and 55 patients surviving 3 years in auto-HSCT and allo-HSCT. Of the auto-HSCT and allo-HSCT recipients, 98.8% and 89.1% had normal or near-normal activity scores (Karnofsky assessment 90–100%) in 3 years post-transplantation, and there was significant difference between the two groups (P=0.015).

Conclusion Auto-HSCT followed by immunotherapy and maintenance chemotherapy might reduce relapse for IR AML-CR1 post-transplantation, and have similar survival compared with allo-HSCT. It is superior to allo-HSCT in quality of life.