Effects of interleukin-3 and granulocyte-macrophage colony-stimulating
factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia
EC Guinan, YS Lee, KD Lopez, S Kohler, DH Oette, E Bruno, H Kozakewich, DG Nathan and R Hoffman
Division of Hematology/Oncology, Children's Hospital, Boston, MA.
Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder
of infancy and childhood presenting with isolated thrombocytopenia that
progresses to marrow failure. The defect in thrombopoiesis is not well
understood nor is the etiology of the progressive marrow failure. No
standard modality of treatment exists. Here, we evaluated the capacity of
marrow cells isolated from five patients with AMT and progressive marrow
failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro
studies demonstrated assayable numbers of CFU-MK from all patient bone
marrows that responded in vitro to the addition of interleukin-3 (IL-3),
granulocyte-macrophage colony-stimulating factor (GM-CSF), or the
combination of both. These findings suggest that the defect in AMT might be
partially correctable by the administration of these cytokines. A Phase
I/II trial of in vivo administration of these same hematopoietins in the
identical patients was conducted in which no significant toxicity was
observed. IL-3 but not GM-CSF administration resulted in improved platelet
counts in two patients and decreased bleeding and transfusion requirement
in the remaining three. No clinical benefit was observed when GM-CSF was
administered after IL-3 pretreatment. Prolonged IL-3 administration has
resulted in platelet increases in an additional two patients. In vitro
responsiveness of CFU- MK to either cytokine did not predict the degree of
clinical response. Although the optimal dose and schedule of IL-3 either
alone or in combination remains to be established, this study suggests that
IL-3 may contribute to the treatment of patients with AMT.
Volume 81,
Issue 7,
pp. 1691-1698,
04/01/1993
Copyright © 1993 by The American Society of Hematology
