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Combined therapy with recombinant granulocyte colony-stimulating factor and
erythropoietin decreases hematologic toxicity from zidovudine
SA Miles, RT Mitsuyasu, J Moreno, G Baldwin, NK Alton, L Souza and JA Glaspy
Division of Hematology-Oncology, UCLA School of Medicine.
Twenty-two patients with acquired immunodeficiency syndrome (AIDS) or
severe AIDS-related complex and multilineage hematopoietic defects were
treated with recombinant granulocyte colony-stimulating factor (G-CSF) and
erythropoietin (EPO) in a phase I/II trial. All patients were neutropenic
and anemic after withdrawal of all bone marrow-suppressive drugs. Daily,
G-CSF was subcutaneously self-administered until an absolute neutrophil
count (ANC) greater than 6,000/microL was achieved and maintained for 2
weeks. Subcutaneous EPO was added to the regimen and the dose increased
until an increase of 15 g/L of hemoglobin was observed. Groups of patients
were administered increasing doses of zidovudine to determine their
tolerance. G-CSF and EPO therapy was continued with dose modification to
maintain an ANC greater than 1,500/microL and hemoglobin greater than 100
g/L. The dose of zidovudine was not altered. All 22 patients responded to
G-CSF with a mean 10-fold increase in neutrophils occurring in less than 2
weeks. Significant increases in CD4 and CD8 cell number, lymphocyte
proliferative response, and bone marrow cellularity were seen. EPO therapy
increased hemoglobin in all 20 evaluable patients within 8 weeks. Sixteen
patients received 1,000 mg and four patients received 1,500 mg of
zidovudine per day. The reinstitution of zidovudine resulted in a decline
in reticulocytes and hemoglobin and the reappearance of transfusion
requirements in eight of the 20 patients, six of whom had the study
medications stopped. No patient had the study medications stopped because
of neutropenia or thrombocytopenia. Toxicities were mild and did not
require dose modifications. Limiting dilution plasma and lymphocyte
co-cultures for HIV as well as serum p24 antigen levels did not change
significantly during G-CSF or combined G- CSF and EPO therapy. HIV p24
antigen decreased significantly with zidovudine therapy. Opportunistic
infections occurred in 14 patients but were successfully treated with
myelosuppressive antimicrobial agents, including ganciclovir, without the
development of neutropenia. These results suggest that combined therapy
with G-CSF and EPO may improve the neutropenia and anemia of AIDS. Combined
therapy may allow the resumption of full-dose zidovudine in most patients
intolerant of the hematologic effects of zidovudine without apparent
alteration of HIV expression or the efficacy of zidovudine.
Volume 77,
Issue 10,
pp. 2109-2117,
05/15/1991
Copyright © 1991 by The American Society of Hematology
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