Efficacy of colony-stimulating factors in acute leukemia

OBJECTIVE: To evaluate the literature describing the safety and efficacy of the hematopoietic colony-stimulating factors (CSFs) for the management of treatment-related adverse effects in patients with acute leukemia. DATA SOURCES: A systematic MEDLINE search of the English-language literatur e (1995-April 2000) was performed to identify all randomized trials evaluat ing CSF use in acute leukemia. The following search terms were used: granul ocyte colony-stimulating factor, filgrastim, granulocyte-macrophage colony- stimulating factor, sargramostim, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute nonlymphocytic leukemia, and acute myelo id leukemia. The references from relevant literature were also examined in order to identify reports not discovered in the MEDLINE search. DATA SYNTHESIS: SIX randomized trials in pediatric ALL, nine in adult AML, and four in adult ALL have examined the safety and efficacy of the CSFs. Tw o of the pediatric trials supported a reduction in either the duration of h ospitalization or in the incidence of febrile neutropenia when a CSF was em ployed during the consolidation or intensification phase of chemotherapy. T he remaining pediatric trials failed to demonstrate a clinical benefit. In adult AML, eight of the nine trials showed a significant decrease in the ti me to neutrophil recovery when a CSF was used. Only one of these trials dem onstrated a decrease in hospital stay and none showed a decreased incidence of infection for patients who received a CSF. Three of the four trials in adult ALL demonstrated the efficacy of a CSF in decreasing the number of da ys to neutrophil recovery. Only one trial demonstrated that a CSF led to a reduction in the number of hospital days. Trials in children or adults have not demonstrated that the CSFs influence the long-term outcome of patients with acute leukemia. CONCLUSIONS: The published studies document a decrease in the time to recov ery from neutropenia when patients with acute leukemia are treated with a C SF. However, a consistent reduction in infectious complications or in the d uration of hospitalization has not been demonstrated when a CSF is used for either pediatric or adult patients. Very limited data exist to support the premise that CSFs meet the criteria established by the American Society of Clinical Oncology for demonstrating the value of these agents. Further car eful study focused on resource utilization and pharmacoeconomics may help t o elucidate how healthcare institutions may most effectively employ CSFs to treat patients with acute leukemia.