Potential use of human stem cell factor as adjunctive therapy for human
immunodeficiency virus-related cytopenias
SA Miles, K Lee, L Hutlin, KM Zsebo and RT Mitsuyasu
Division of Hematology-Oncology, UCLA AIDS Clinical Research Center
90024-1793.
Hematopoietic dysfunction with peripheral cytopenias is a common
complication of human immunodeficiency virus (HIV) infection. Symptomatic
anemia is the most common cytopenia and occurs in the presence and absence
of myelosuppressive drug therapy such as zidovudine. Drug-induced
neutropenia and immune thrombocytopenia are also frequent and occur in up
to 50% of acquired immunodeficiency syndrome (AIDS) patients. Attempts to
reduce the impact of bone marrow failure have focused on dose reduction of
zidovudine, ganciclovir, and chemotherapy, and the use of recombinant
hematopoietic hormones such as erythropoietin (EPO) and granulocyte
colony-stimulating factor (G-CSF). Despite these maneuvers, approximately
30% of patients with AIDS receiving zidovudine will become
transfusion-dependent. This has led to investigations of other cytokines
that may increase blood cell formation. The recent identification of
decreased number and proliferation of hematopoietic progenitors in patients
with HIV infection suggests that agents which have activity on progenitor
cell pools may have clinical utility. We demonstrate that human stem cell
factor (HuSCF) increases burst-forming unit-erythroid (BFU-E), colony-
forming unit-granulocyte-monocyte (CFU-GM), and CFU-Mix formation in vitro
in normal and HIV-infected individuals. HuSCF also decreases the
sensitivity of BFU-E to inhibition by zidovudine without altering HIV
replication in lymphocytes or monocytes, altering peripheral blood
mononuclear cell proliferation to phytohemagglutinin (PHA) and
interleukin-2 (IL-2) or altering the effectiveness of zidovudine or
dideoxyinosine in inhibiting HIV replication in lymphocytes or monocytes.
These studies suggest that HuSCF may have clinical utility in HIV infection
as an adjunctive treatment for HIV-related cytopenias.
Volume 78,
Issue 12,
pp. 3200-3208,
12/15/1991
Copyright © 1991 by The American Society of Hematology
