In conclusion, hematopoietic
growth factors have been shown to enhance the recovery and function of circulating WBCs after standard-dose
cancer therapy or high-dose
cancer therapy with ABMT, and preliminary data strongly suggests that these agents may have the ability to restore leukocyte numbers and competence in
AIDS,
myelodysplastic syndromes, and other marrow failure states. Phase I and II trials of
GM-CSF in patients with
AIDS,
cancer, marrow failure states, and following
bone marrow transplantation have been published, and limited phase III randomized trial experiences have been reported as well. Overall,
GM-CSF represents a fascinating molecule with which to modulate human hematopoiesis in vivo. The multilineage stimulatory effects of
GM-CSF that are evident in vitro have not been striking or consistent in clinical trials. However, the effects of
GM-CSF on the production and function of mature neutrophils, monocytes, and eosinophils have been noted in the vast majority of clinical scenarios in which this
cytokine has been tested. The clinical benefits of
GM-CSF have, to date, only been proven in large-scale randomized studies of recovery from ABMT for lymphoid
neoplasms. However, further data regarding the use of
GM-CSF in other clinical settings have been generated, and the final results are eagerly anticipated by the oncology community. The beneficial effects of
GM-CSF following ABMT consisted not only of a shorter period of absolute
neutropenia, but also fewer significant
infections, a diminished requirement for intravenous
antibiotic administration, and a shorter overall duration of inpatient hospitalization. The use of
GM-CSF in clonal disorders of hematopoiesis, such as myelodysplasia or
myeloid leukemias, requires caution before such applications can be routinely recommended, and the demonstration of safety in this setting from large randomized trials will be needed. Preliminary data from small randomized trials suggests that the incidence of evolution to
leukemia in patients with myelodysplasia and the number of patients with regrowth of
leukemia after induction treatment in relapsed patients with AML may not be significantly different than in patients who do not receive
GM-CSF. Various neutropenic conditions (eg, idiopathic or congenital) may respond clinically to hematopoietic
growth factors such as
GM-CSF. Patients treated for 3 to 15 months continue to respond with significantly increased granulocytes and resolution of prior
infection. The subcutaneous route of administration is convenient and patients seem to accept it readily. It is difficult to determine the extent to which adjunctive
therapy with
GM-CSF will be cost effective.(ABSTRACT TRUNCATED AT 400 WORDS)