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.
Yoshimi
Akihide
A
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Nannya
Yasuhito
Y
Sakata-Yanagimoto
Mamiko
M
Oshima
Kumi
K
Takahashi
Tsuyoshi
T
Kanda
Yoshinobu
Y
Motokura
Toru
T
Chiba
Shigeru
S
Kurokawa
Mineo
M
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