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

Publication ,  Journal Article
Lemoli, RM; Gasparetto, C; Scheinberg, DA; Moore, MA; Clarkson, BD; Gulati, SC
Published in: Blood
April 15, 1991

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 micrograms/mL), reactive with distinct antigens found on early myeloid cells and monocytes, used alone and in combinations; (2) 4-Hydroperoxycyclophosphamide (4-HC) (80 mumol/L or 100 mumol/L) alone; or (3) combined with VP-16 (5 micrograms/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.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

April 15, 1991

Volume

77

Issue

8

Start / End Page

1829 / 1836

Location

United States

Related Subject Headings

  • Transplantation, Autologous
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Interleukin-3
  • Interleukin-1
  • Immunosuppression Therapy
  • Immunology
  • Humans
  • Hematopoietic Stem Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lemoli, R. M., Gasparetto, C., Scheinberg, D. A., Moore, M. A., Clarkson, B. D., & Gulati, S. C. (1991). Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination. Blood, 77(8), 1829–1836.
Lemoli, R. M., C. Gasparetto, D. A. Scheinberg, M. A. Moore, B. D. Clarkson, and S. C. Gulati. “Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination.Blood 77, no. 8 (April 15, 1991): 1829–36.
Lemoli RM, Gasparetto C, Scheinberg DA, Moore MA, Clarkson BD, Gulati SC. Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination. Blood. 1991 Apr 15;77(8):1829–36.
Lemoli RM, Gasparetto C, Scheinberg DA, Moore MA, Clarkson BD, Gulati SC. Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid-specific monoclonal antibodies and drugs in combination. Blood. 1991 Apr 15;77(8):1829–1836.

Published In

Blood

ISSN

0006-4971

Publication Date

April 15, 1991

Volume

77

Issue

8

Start / End Page

1829 / 1836

Location

United States

Related Subject Headings

  • Transplantation, Autologous
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Interleukin-3
  • Interleukin-1
  • Immunosuppression Therapy
  • Immunology
  • Humans
  • Hematopoietic Stem Cells