Autologous bone marrow transplantation in acute leukemia: A phase I study of in vitro treatment of marrow with 4-hydroperoxycyclophosphamide to purge tumor cells

H. Kaizer, R. K. Stuart, R. Brookmeyer, W. E. Beschorner, H. G. Braine, W. H. Burns, D. J. Fuller, M. Korbling, K. F. Mangan, R. Saral

Research output: Contribution to journalArticlepeer-review

Abstract

This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide(4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 μg/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 μg/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 μg/mL. At 120 μg/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 μg/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.

Original languageEnglish (US)
Pages (from-to)1504-1510
Number of pages7
JournalBlood
Volume65
Issue number6
DOIs
StatePublished - 1985

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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