Autologous bone marrow transplantation in acute myelogenous leukemia: In vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination Journal Article

  

Authors:	Lemoli, R. M.; Gasparetto, C.; Scheinberg, D. A.; Moore, M. A. S.; Clarkson, B. D.; Gulati, S. C.
Article Title:	Autologous bone marrow transplantation in acute myelogenous leukemia: In vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination
Abstract:	We report the results of a preclinical study comparing four different purging protocols using a promyelocytic human cell line HL-60 and myeloid leukemic progenitor cells (colony-forming unit-leukemic [CFU-L]) from acute myelogenous leukemia (AML) patients assayed in semisolid culture. We studied the antileukemic effect of (1) Single-cycle complement-mediated lysis by two different monoclonal antibodies (MoAbs) (M195 [CD33] and F23 [CD13] 40 μg/mL), reactive with distinct antigens found on early myeloid cells and monocytes, used alone and in combinations; (2) 4-Hydroperoxycyclophosphamide (4-HC) (80 μmol/L or 100 μmol/L) alone; or (3) combined with VP-16 (5 μg/mL) and (4) a cocktail of 1 through 3 as above (combined immunochemotherapy). More than 4 logs of HL-60 tumor cell elimination were observed after 1 hour of incubation with both MoAbs plus 4-HC + VP-16 while the single treatment (immunotherapy or chemotherapy) provided 1.5 and 3.5 logs of colony-forming inhibition, respectively. When the same protocols were tested on cryopreserved leukemic cells from eight patients with AML, we observed a mean value of CFU-L inhibition of 92.3% ± 2.5% SD, 95.5% ± 1.4% SD, and 99% ± 0.8% SD after MoAbs and complement lysis, 4-HC, and 4-HC + VP-16 treatment, respectively. The combined treatment of MoAbs and 4-HC + VP-16 produced more than 3-log reduction of CFU-L colony formation. By comparison, the mean recovery of committed normal bone marrow progenitors after incubation with MoAbs and complement was 12% for CFU-granulocyte-macrophage (CFU-GM), 22.9% for burst-forming unit erythroid (BFU-E), and the recovery following 4-HC + VP-16 treatment was 4.4% for CFU-GM and 5.6% BFU-E. In subsequent experiments, highly purified CD34+ blast cells, enriched by positive selection, and stimulated in liquid culture by cytokines (interleukin-1 [IL-1], IL-3, and combination of both) or MO-conditioned medium (MoCM), demonstrated that immunochemotherapy spares hematopoietic colony-forming cells earlier than day 14 CFU-GM, in vitro.
Keywords:	adult; clinical article; controlled study; aged; comparative study; etoposide; cell line; cyclophosphamide; monoclonal antibody; antibodies, monoclonal; acute myeloblastic leukemia; hematopoietic stem cells; cytotoxicity, immunologic; bone marrow transplantation; colony-forming units assay; transplantation, autologous; immunosuppression; interleukin-1; middle age; interleukin-3; leukemia, myelocytic, acute; human; male; female; priority journal; article; support, non-u.s. gov't
Journal Title:	Blood
Volume:	77
Issue:	8
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	1991-04-15
Start Page:	1829
End Page:	1836
Language:	English
PUBMED:	2015406
PROVIDER:	scopus
DOI:	10.1182/blood.V77.8.1829.1829
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0025818594&partnerID=40&md5=b3a3f443be1d768e95757c51ee8e59e7
Notes:	Cristina Gasparetto's first name is misspelled on the original publication -- Article -- Source: Scopus

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