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

Int J Clin Pharm. 2015 Feb;37(1):44-52. doi: 10.1007/s11096-014-0036-5. Epub 2014 Nov 29.

Abstract

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/m(2) and Ara-c 6 g/m(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Busulfan / administration & dosage*
  • Child
  • Cyclophosphamide / administration & dosage*
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide
  • Busulfan