Granulocyte-monocyte and Granulocyte-Colony Stimulating Factors in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a heterogenous group of clonal disorders of hemopoiesis entailing hypoproliferative and ineffective hematopoiesis. The biology of MDS may relate to uncoupling of hemopoietic cellular differentiative and proliferative programs. The MDS provide a clinical setting for evaluating the evolution of relative benign hematologic disorders into frankly malignant diseases similar to acute myelogenous leukemia (AML). In vitro marrow hemopoietic cultures were utilized to evaluate the effect of granulocyte-monocyte colony-stimulating factor (GM-CSF) and granulocyte-colony stimulating factors (G-CSF) on proliferating differentiative and regenerative responsiveness of marrow cells from MDS patients. We determined possible differing effects of G-CSF and GM-CSF in morphological and cytogenetical subgroups of MDS patients. G-CSF was able to induce granulocytic differentiation of enriched hemopoietic precursors from MDS patients, generally without increased clonal self-generation. G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T) and those with normal cytogenetics. These findings provided a biologic rationale for in vivo clinical trials using G-CSF in MDS patients. Prospective investigations will be necessary to determine the possible utility of such in vitro studies for designing future in vivo clinical trials with these colony stimulating factors.