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Recombinant human interleukin-3 and recombinant human granulocyte-
macrophage colony-stimulating factor administered in vivo after high- dose
cyclophosphamide cancer chemotherapy: effect on hematopoiesis and
microenvironment in human bone marrow
A Orazi, G Cattoretti, R Schiro, S Siena, M Bregni, M Di Nicola and AM Gianni
Division of Anatomic Pathology and Cytology, Istituto Nazionale per lo
Studio e la Cura dei Tumori, Milan, Italy.
The effects on bone marrow (BM) cell proliferation and differentiation of
recombinant human interleukin-3 (rhIL-3) and recombinant human
granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered
after high-dose (7 g/m2/d) cyclophosphamide (HD-CTX) chemotherapy were
studied in nine patients with malignancies without BM involvement and in
three control patients. rhIL-3 at a dose of 1 to 5 micrograms/kg/day was
administered for 14 to 18 days by continuous intravenous (i.v.) infusion
and rhGM-CSF was administered at a dose of 5.5 micrograms/kg/day for 14
days. Changes induced by cytokine treatment were assessed by
morphoimmunohistochemical analysis of BM biopsies. Comparison was made in
the cytokine-treated groups and with control patients who received HD-CTX
alone. BM cellularity and the myeloid/erythroid (ME) ratio were lower in
rhIL-3-treated than in rhGM- CSF-treated patients, but in both groups it
was significantly higher than in the controls. The proportion of BM cells
stained by PC10, a monoclonal antibody (MoAb) recognizing a
proliferation-associated nuclear protein (PCNA), increased from 6.78% to
21.18% (P less than .02) after rhIL-3, and from 5% to 35.33% (P less than
.001) after rhGM- CSF; no increase was observed in the control group. The
frequency of CD34+ BM cells was unchanged after rhIL-3 (P = NS) and
decreased after rhGM-CSF (P less than .001). In both groups, most of the
PC10+ cells were represented by promyelocytes and myelocytes with no
increase in blast cell numbers. rhIL-3-treated BM showed an increased
number of megakaryocytes and increased proliferative activity of erythroid
cells as compared with rhGM-CSF cases. BM stroma changes observed in both
treated groups included endothelial cell proliferation, increased BM
macrophage concentration, and increase in BM fibroblasts as detected with
an anti-nerve growth factor receptor antibody. In most rhIL-3- treated
cases, BM fibrosis developed after treatment. The same effect was not
observed in rhGM-CSF patients.
Volume 79,
Issue 10,
pp. 2610-2619,
05/15/1992
Copyright © 1992 by The American Society of Hematology
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