Use of cytokines in the treatment of acute myelocytic leukemia: a critical review.

PURPOSE

The colony-stimulating factors (CSFs) have been evaluated in patients with acute myelocytic leukemia (AML), both as potential priming agents and during and/or following induction chemotherapy to shorten the period of myelosuppression. The purpose of this review is to evaluate critically the safety and efficacy of the CSFs, primarily granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF), in the treatment of patients with AML.

METHODS

All phase III trials that have either been presented or published that used CSFs during and/or following induction chemotherapy in patients with de novo AML are discussed. Relevant background information and future directions are also addressed.

RESULTS AND CONCLUSION

There have been six phase III trials that used either GM-CSF or G-CSF in induction therapy in patients with AML. It is difficult to compare these trials due to differences in patient age, induction therapy administered, disease characteristics, whether leukemia response or documentation of marrow hypoplasia was required before cytokine use, and the different cytokines administered during the study. In particular, the timing of CSF administration in relation to the chemotherapy may be important due to the different biologic effects these agents may have on leukemia cells, such as leukemia cell recruitment. Most of these studies administered either GM-CSF or G-CSF before or during induction therapy, as well as following completion of chemotherapy until neutrophil recovery. Only one of six trials required documentation of marrow hypoplasia before CSF use. Despite these differences, administration of either GM-CSF or G-CSF was found to be safe without an increase in acute toxicity or an increase in relapse rates. In addition, most trials demonstrated a significant improvement in neutrophil recovery, with several trials demonstrating an improvement in complete remission and overall survival rates. Therefore, the use of selected CSFs may be of benefit following induction chemotherapy in those patients with AML who are at increased risk for early morbidity and mortality.