Clinical and experimental evidence revealing Ph1-negative hematopoietic stem cells in the majority of chronic myelogenous leukemia (CML) patients, suggests that autologous bone marrow transplantation (ABMT) may represent a therapeutic approach for these patients. It was the aim of the present study to evaluate the efficacy of the cyclophosphamide derivative mafosfamide as a marrow purging agent in a group (n = 15) of CML patients. Chemical purging was followed by a short-term liquid culture phase supplemented with recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Mafosfamide (100 μg/ ml) incubation induced a marked inhibition of progenitor cell growth, the percentages of surviving CFU-GEMM, BFU-E, and CFU-GM being 3.4, 5.4, and 4.9, respectively. At the cytogenetic level, the purging procedure failed to show any modulating effect on Ph1-negative clones in 9/15 cases. In contrast, 6/15 cases showed a significant increase in the mean (± SD) percentage of Ph1-negative metaphases in response to rGM-CSF (46 ± 26, p ≤ 0.05), mafosfamide incubation (53 ± 12, p ≤ 0.01), and the combination of mafosfamide incubation plus rGM-CSF (63 ± 29, p ≤ 0.025). Immunological analysis revealed that mafosfamide incubation induced a significant enrichment of MY10 (28 ± 9, p ≤ 0.05), IL2-receptor (34 ± 10, p ≤ 0.05) B73.1-positive cells (25 ± 9, p ≤ 0.05). Four mafosfamide-responsive patients with CML in second chronic phase have been autografted with mafosfamide purged marrow. In all patients a Ph1-negative phase lasting 5-14 months was observed. In conclusion, it appears that (a) in a subgroup of CML patients mafosfamide purging is effective in reducing the size of the malignant clone and might induce through its cytotoxic and immune actions a modification of the balance between leukemic and normal clones, and (b) this experimental approach may be used as a screening test to select patients to undergo marrow harvest and ABMT with mafosfamide purged marrow.
|Number of pages||9|
|Journal||Bone Marrow Transplantation|
|Publication status||Published - 1991|
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