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In vitro marrow purging in chronic myelogenous leukemia: effect of mafosfamide and recombinant granulocyte--macrophage colony-stimulating factor.

PIOVANI, Giovanna;
1991-01-01
1991
Altra università italiana
LS3_3 Cell cycle and division
LS7_6 Gene therapy, stem cell therapy, regenerative medicine
BONE MARROW TRANSPLANTATION
2-s2.0-0026052783
WOS:A1991GN28600005
Inglese
Internazionale
8
265
273
8
1756324
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 micrograms/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 less than or equal to 0.05), mafosfamide incubation (53 +/- 12, p less than or equal to 0.01), and the combination of mafosfamide incubation plus rGM-CSF (63 +/- 29, p less than or equal to 0.025). Immunological analysis revealed that mafosfamide incubation induced a significant enrichment of MY10 (28 +/- 9, 0.05) B73.1-positve cells (25 +/- 9, p less than or equal to 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.
Adult; Aged; Antineoplastic Agents; Bone Marrow Purging; Bone Marrow Transplantation; Colony-Forming Units Assay; Cyclophosphamide; Evaluation Studies as Topic; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia; Myeloid; Chronic; Atypical; BCR-ABL Negative; Chronic-Phase; Male; Middle Aged
7
info:eu-repo/semantics/article
262
Carlo Stella, C; Mangoni, L; Piovani, Giovanna; Almici, C; Garau, D; Caramatti, C; Rizzoli, V.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/35148
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