Recombinant Myeloid Hematopoietic Growth Factors and Clinical Stimulation of Acute Myeloid Leukemia Cells: A Narrative Review.
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BACKGROUND: The advent of molecularly cloned hematopoietic growth factors (rhuG-CSF and rhuGM-CSF) enhanced the safety in treating acute myeloid leukemia (AML) by reducing the duration of neutropenia and thus decreasing the risks for infection. However, early in vitro studies demonstrated leukemia cell proliferation in response to these agents, raising reasonable concerns related to whether these factors can cause or contribute to relapse or progression of AML. SUMMARY: Clinical studies using recombinant myeloid hematopoietic growth factors have supported their safety, as there is little or no clear evidence for an association with an increased risk of relapse in AML in patients, regardless of the hematopoietic growth factor used, or whether the setting of AML is newly diagnosed or relapsed/refractory. One exception may be in the pediatric population, though this effect might reflect a different isoform of the G-CSF receptor expressed on the AML cells, as this truncated receptor is also seen in severe congenital neutropenia and aplastic anemia and underlies the increased myeloid malignancies that develop in these diseases after long-term exposure to growth factors. KEY MESSAGES: The current data support the use of rhuG-CSF and rhuGM-CSF in most patient populations with AML. Future studies should explore the factors influencing hematopoietic growth factor sensitivity in AML subpopulations to guide therapeutic decisions.