Unfortunately, CSF-mediated hematopoietic restoration after intensive chemotherapy has not proved able to eliminate the nadir induced by dose-intensive chemotherapy. In addition, cumulative neutropenia and thrombocytopenia have proved persistently troublesome, limiting the ability of investigators to maintain chemotherapy dosing over multiple cycles. Both clinical and animal data indicate that pre-chemotherapy administration of GM-CSF, may not only enhance the pool of CSF-responsive progenitors but can also induce a state of chemoprotection for bone marrow progenitors that might have a positive clinical effect on the prevention of myelosuppression. IL-3, an early acting cytokine which enhances the numbers of multiple normal hematopoietic elements, also is a logical candidate for a pre-chemotherapy administration schedule. It has been observed that the administration of IL-3 to monkeys for several days, followed by the subsequent administration GM-CSF, appears to markedly enhance the activity of GM-CSF in provoking leucocytosis, and perhaps also thrombocytosis and reticulocytosis during the time that GM-CSF is being administered. Based on these properties, it seems important to consider the use of IL-3 to enhance the stem cell pool prior to chemotherapy and the administration of GM-CSF afterward to stimulate differentiation of the IL-3-induced progenitors.
