Acute myeloid leukemia (AML) and
acute lymphoblastic leukemia (ALL) are malignant clonal disorders of the blood system requiring intensive and long-term cytotoxic treatment. Current
chemotherapy protocols not only target the malignant cell, but are also highly toxic to normal hematopoietic cells as well.
Leukemia patients thus experience prolonged times of
neutropenia,
thrombocytopenia, and
anemia, which increase the risk for secondary complications like
infections and
bleeding. Twenty years ago
leukemia patients were considered the ideal candidates to benefit from accelerated recovery of
cytopenias by treatment with recombinant
cytokines. Moreover, based on in vitro data, it was hypothesized that myeloid
growth factors may sensitize AML cells to
cytotoxic agents. Numerous clinical trials have documented the
biologic activity of granulocyte and granulocyte-macrophage
growth factors to accelerate neutrophil recovery after
chemotherapy. However, there is high-level evidence that these myeloid
growth factors neither reduce the incidence of severe
infections nor improve the outcome of AML patients. Evidence from ALL trials is mixed with some studies suggesting a reduction of severe
infections by myeloid
growth factors whereas others report no effect. Most studies of acute
leukemia patients suggested that myeloid
growth factors are safe to use, however, a negative impact on event-free survival was found in one trial and an increased risk for secondary AML was reported in pediatric ALL patients. Thrombopoietins have not led so far to a significant increase in platelet numbers in
leukemia patients.
Chemokine receptor antagonists are now being evaluated in clinical trials for synergistic effects with
chemotherapy and will be discussed briefly.
Cytokine development mirrors the great advances that have been achieved in the understanding of regulatory mechanisms in hematopoiesis. As this understanding grows, new drugs and new applications will emerge.