The hematopoietic growth factors in acute leukemia: a European perspective.
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.
Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. heuser.michael@mh-hannover.de
Michael
M
Heuser
Arnold
A
Ganser
Dieter
D
Hoelzer
D000208:Acute Disease; D005060:Europe; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*
D016298:Hematopoietic Cell Growth Factors