Effects of recombinant human interleukin-3 on human hematopoietic progenitor and precursor cells in vivo.
DNA-synthesis rates and concentrations of bone marrow (BM) and peripheral blood (PB) progenitor cells were studied in 22 patients treated with recombinant human interleukin-3 (rhIL3) as part of a clinical phase I/II study. Recombinant hIL3 at doses of 60 to 500 micrograms/m2 was administered by subcutaneous bolus injection for 15 days to 13 patients with solid tumors and preserved hematopoietic function and to nine patients with bone marrow failure, including five with myelodysplastic syndromes. Following treatment with rhIL3, the percentage of actively cycling BM erythroid (BFU-E) and multilineage (CFU-GEMM) progenitors in patients with preserved hematopoietic function increased from 16% to 36% (P less than .05) and from 10% to 40% (P less than .01), respectively. The DNA-synthesis rates of early and late granulocyte macrophage progenitor cells increased from 11% to 26% (CFU-GM day 14; P less than .02) and from 13% to 30% (CFU-GM day 7; P less than .05). There was an increase in BM cellularity from 37% to 58%, and of the myeloid to erythroid ratio from 1.4 to 3.2, while the concentration of marrow progenitors on a per cell basis was unchanged or slightly decreased. The frequencies of blast cells in the BM were unchanged. Mean levels of PB CFU-GM day 14 and CFU-GEMM were 100% and 72% above baseline values after 7 days of rhIL3 but only 25% and 28% above initial levels at the end of treatment. Peripheral blood BFU-E were reduced in the majority of patients with normal marrow after both 7 and 15 days of rhIL3. No augmentation of circulating BFU-E and CFU-GEMM was seen in 5 patients with MDS who had few or no PB BFU-E or CFU-GEMM initially. Total leukocyte, neutrophil, and eosinophil counts increased significantly (P less than .01) in 21 of 22 patients with a peak response after a median of 13 days of rhIL3. While a small increase in reticulocytes was not accompanied by an elevation of the hemoglobin or hematocrit, platelet counts increased by 50% in patients with preserved marrow function. Thus, rhIL3 induces a multilineage response in vivo, apparently by stimulating proliferation of multipotential and lineage-restricted progenitors. It remains to be determined whether this is due to direct or indirect effects on the progenitor cells.
Department of Hematology, University of Frankfurt, FRG.
O G
OG
Ottmann
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A
Ganser
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Seipelt
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M
Eder
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Schulz
D
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Hoelzer
D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells; D001855:Bone Marrow Diseases / Q000188:drug therapy / Q000473:pathology; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D015672:Erythroid Precursor Cells / Q000166:cytology; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology* / Q000627:therapeutic use; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology
D007377:Interleukin-3; D011994:Recombinant Proteins; D004247:DNA