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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, RK Stuart, R Brookmeyer, WE Beschorner, HG Braine, WH Burns, DJ Fuller, M Korbling, KF Mangan and R Saral
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 micrograms/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 micrograms/mL.
Nevertheless, only one transplant-related death and otherwise full
hematologic recovery was observed at concentrations of 4HC up to 100
micrograms/mL. At 120 micrograms/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
micrograms/mL), satisfactory hematologic recovery can be obtained, despite
elimination of detectable hematopoietic progenitors.
Volume 65,
Issue 6,
pp. 1504-1510,
06/01/1985
Copyright © 1985 by The American Society of Hematology
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