High doses of cyclophosphamide, etoposide and total body irradiation followed by autologous stem cell transplantation in the management of patients with chronic myelogenous leukemia

Bone Marrow Transplant. 1994 Jul;14(1):57-61.

Abstract

Eighteen patients with chronic myelogenous leukemia (CML) in chronic (9 patients) or advanced phases (9 patients) underwent autologous bone marrow transplantation (BMT) with a preparative regimen using high doses of cyclophosphamide, etoposide and total body irradiation (CY-VP16-TBI): cyclophosphamide 60 mg/kg daily on days 1 and 2; VP16 250 mg/m2 twice daily on days 1-3 and TBI 1020 cGy in six fractionated doses on days 5-7. Autologous marrow cells were reinfused on day 8. Three of the 8 patients in late chronic phase Philadelphia (Ph) chromosome-positive CML (37%) achieved a cytogenetic response, with Ph suppression to 25%, 29% and 44% Ph-positive metaphases, respectively, and lasting for 11, 1 and 3 months, respectively. The median duration of chronic phase following BMT was 26+ months (range 2-33+ months). One patient with Ph-negative, BCR-rearranged, chronic phase CML had a decrease of the BCR-rearranged band to 10% of pretreatment levels, which persisted for 6 months. None of the 9 patients with advanced CML phases (5 in second chronic, 1 in blastic, 3 in accelerated) achieved meaningful cytogenetic responses. Their median survival was 7 months from the time of BMT. Toxicities were mostly related to myelosuppression, particularly thrombocytopenia. Febrile episodes developed in 16 patients (89%). Treatment-related deaths occurred in 2 patients (11%). In summary, autologous BMT using a TBI-containing regimen had acceptable toxicity. Future investigations will evaluate the additional benefit of purged autologous stem cell transplantation in patients with chronic phase CML.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage*
  • Etoposide / administration & dosage*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / radiotherapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / drug therapy
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / radiotherapy
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / therapy*
  • Male
  • Middle Aged
  • Transplantation, Autologous
  • Whole-Body Irradiation

Substances

  • Etoposide
  • Cyclophosphamide