A myeloablative conditioning regimen for patients with impaired cardiac function undergoing allogeneic stem cell transplantation: reduced cyclophosphamide combined with etoposide and total body irradiation

Am J Hematol. 2008 Aug;83(8):635-9. doi: 10.1002/ajh.21208.

Abstract

To circumvent the cardiac toxicity of high-dose cyclophosphamide (CY) in the myeloablative conditioning for those with cardiac comorbidity, we developed a new cardiac sparing conditioning regimen (VP/rCY/TBI) composed of 12 Gy of total body irradiation (TBI), etoposide (VP-16) (40 mg/kg), and reduced CY (40 mg/kg). We assessed the feasibility of this regimen by retrospectively comparing the outcome of VP/rCY/TBI recipients (n = 18) with that of CY/TBI recipients (n = 140). VP/rCY/TBI recipients had significantly higher cumulative dose of anthracyclines, lower ejection fraction (EF), and poorer Karnofsky performance scales (KPS) than CY/TBI recipients. The cumulative incidences of disease progression were 34.9% in VP/rCY/TBI recipients and 19.0% in CY/TBI recipients (P = 0.33). Despite poorer KPS and more cardiac comorbidity in the VP/rCY/TBI recipients, no difference in the nonprogression mortality rates was observed among recipients of the two regimens (17.5 and 14.3%, respectively, P = 0.96). Severe cardiac toxicity within 28 days after transplantation occurred in 5.9 and 3.6% of VP/rCY/TBI and CY/TBI recipients, respectively (P = 0.64). Graft rejection was not observed in VP/rCY/TBI recipients. There is a possibility that VP/rCY/TBI regimen can be safely administered for patients with pretransplantation cardiac comorbidity while preserving antineoplastic effects. These observations merit further prospective study.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Combined Modality Therapy
  • Comorbidity
  • Cyclophosphamide / administration & dosage*
  • Etoposide / administration & dosage
  • Female
  • Heart Diseases / epidemiology*
  • Hematologic Neoplasms / epidemiology*
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Male
  • Middle Aged
  • Myeloablative Agonists / administration & dosage*
  • Retrospective Studies
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Whole-Body Irradiation

Substances

  • Myeloablative Agonists
  • Etoposide
  • Cyclophosphamide