A myeloablative conditioning regimen for patients with impaired cardiac function undergoing allogeneic stem cell transplantation: reduced cyclophosphamide combined with etoposide and total body irradiation.
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.
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Akihide
A
Yoshimi
Yasuhito
Y
Nannya
Mamiko
M
Sakata-Yanagimoto
Kumi
K
Oshima
Tsuyoshi
T
Takahashi
Yoshinobu
Y
Kanda
Toru
T
Motokura
Shigeru
S
Chiba
Mineo
M
Kurokawa
D000293:Adolescent; D000328:Adult; D003131:Combined Modality Therapy; D015897:Comorbidity; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology*; D019337:Hematologic Neoplasms / Q000453:epidemiology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D019653:Myeloablative Agonists; D005047:Etoposide; D003520:Cyclophosphamide