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Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as an Adjunct to Autologous Hemopoietic Stem Cell Transplantation for Lymphoma

Ranjana Advani, MD; Nelson J. Chao, MD; Sandra J. Horning, MD; Karl G. Blume, MD; David K. Ahn, PhD; Kathleen R. Lamborn, PhD; Nancy C. Fleming, BSN; Eric M. Bonnern, MD; and Peter L. Greenberg, MD
[+] Article, Author, and Disclosure Information

Grant Support: In part by Schering-Plough research funds.

Requests for Reprints: Peter Greenberg, MD, Division of Hematology, S161, Stanford University Medical Center, Stanford, CA 94305.

Current Author Addresses: Drs. Advani, Chao, Blume, Greenberg, and Ms. Fleming: Division of Hematology, S161, Stanford University Medical Center, Stanford, CA 94305.

Dr. Horning: Division of Oncology, M211, Stanford University Medical Center, Stanford, CA 94305.

Drs. Ahn and Lamborn: Biostatistics Division, Northern California Cancer Center, 1301 Shoreway Road, Suite 425, Belmont, CA 94002.

Dr. Bonnern: Schering-Plough Research, 2000 Galloping Hill Road, Kenilworth, NJ 07033.

© 1992 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1992;116(3):183-189. doi:10.7326/0003-4819-116-3-183
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Objective: To determine the hemopoietic effects of recombinant human granulocyte-macrophage colonystimulating factor (GM-CSF) in patients having autologous hemopoietic stem cell transplantation for Hodgkin or non-Hodgkin lymphoma.

Design: Placebo or GM-CSF was administered after bone marrow or peripheral blood stem cell transplantation or both in a randomized, double-blind phase III trial by daily intravenous infusion (10 µg/kg body weight) until absolute neutrophil counts reached ≥ 1000/mm3 on 3 consecutive days.

Setting: Bone marrow transplantation unit in a university hospital.

Patients: Sixty-nine consecutive patients with Hodgkin or non-Hodgkin lymphoma received GM-CSF (36 patients) or placebo (33 patients).

Measurements and Main Results: Patients who received GM-CSF achieved absolute neutrophil counts 500/mm3 (median, 12 compared with 16 days, P = 0.02) and absolute neutrophil counts ≥ 1000/mm3 (median, 15 compared with 24 days, P< 0.001) more quickly than patients who received placebo. Multivariate analysis indicated that use of GM-CSF, peripheral blood stem cells, and unpurged bone marrow were the strongest predictors for early neutrophil recovery > 500/mm3. Bacterial infections were significantly reduced in the GM-CSF group (P = 0.04). Delayed engraftment (neutrophils < 500/mm3 at day 30) occurred in 26% and 17% of the placebo and GM-CSF groups, respectively, and correlated with the absence of detectable myeloid progenitor cells (colony-forming unitsgranulocyte macrophage, CFU-GM) (P < 0.001) in marrow aspirate specimens obtained on day 15. Time to platelet independence, duration of hospital stay, severe adverse reactions, relapse, and disease-free survival rates did not differ significantly between the two groups.

Conclusions: Administration of GM-CSF after autologous hemopoietic stem cell transplantation in patients with lymphoma resulted in accelerated myeloid recovery, particularly in patients who received peripheral blood stem cells and nonpurged bone marrow, and was associated with a decreased incidence of bacterial infections.





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