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

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. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.