Effect of High-Dose Methotrexate with Citrovorum Factor on Human Granulopoiesis1

The present studies were performed to delineate the effect of high-dose methotrexate with citrovorum factor rescue on the measurable compartments of human granulopoiesis, including peripheral blood cells and bone marrow stem cells committed to granulopoiesis-monocytopoiesis. Parameters of granulo poiesis were determined during the first course of high-dose methotrexate with citrovorum factor rescue in five patients, and during four consecutive courses in one patient. The remarkably mild toxicity of high-dose methotrexate with citrovorum factor rescue reported in clinical studies was substantiated on the level of the committed stem cell compartment. The data suggest a higher sensitivity of in vitro colony-forming units in agar culture as compared to the more mature granulopoietic cells and document the exquisite sensitivity and regenerating ca pacity of erythroid precursors after this type of chemotherapy.