A modified busulfan and cyclophosphamide preparative regimen for allogeneic transplantation in myeloid malignancies

Background Busulfan/cyclophosphamide (Bu/Cy) is commonly used as a standard conditioning regimen without total body irradiation for patients with hematological myeloid malignancies undergoing hematopoietic stem cell transplantation (HSCT). Objective To develop a new myeloablative conditioning regimen incorporating fludarabine (Flu) and cytarabine (Ara-c). Setting A tertiary blood disease hospital in Tianjin, China. Methods A Bu/Cy preparative regimen was used, modified by Flu 90 mg/m2 and Ara-c 6 g/m2 in 57 unselected patients (median age 37 years) with hematological myeloid malignancies. The patients were to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirteen patients had high-risk leukemia, fifty patients had HLA matched sibling donors while seven patients had HLA mismatched sibling donors. Cy was given 50 mg/kg/day for 2 days while Bu was given 3.2 mg/kg/day intravenously for 3 days. Main outcome measure Post-transplant donor chimerism, relapse tendency and minimal residual disease. Results Extramedullar toxicity was relatively limited; the incidence of treatment-related mortality (TRM) within 100 days was 3.5 %. The incidence of grade II–IV, grade III–IV acute graft versus host disease (GVHD) and chronic GVHD of the evaluable patients were 21.1, 8.8 and 36.4 %, respectively. With a median follow up of 59 (13–96.5) months, TRM and relapse rate (RR) at eight years were 24.1 ± 5.8 and 14.7 ± 4.8 %, respectively. Disease free survival at eight years was 67.9 ± 6.2 % for the entire group, 60.0 ± 8.9 % for patients with AML, 77.3 ± 8.9 % for patients with CML, 70.0 ± 6.5 and 42.9 ± 18.7 % or matched sibling and mismatched sibling HSCT respectively. Conclusion The new regimen was associated with a low relapse rate, low incidence and severity of graft versus host disease and satisfactory survival for patients with myeloid malignancies.