Selective metaphasic blockade of erythroblasts in the bone marrow of patients treated sequentially with recombinant human erythropoietin and vincristine.

In the course of a phase I-II clinical study exploring the therapeutic potential of recombinant human erythropoietin in malignancy-associated anemias, a significant morphologic aspect was found in the marrow aspirates in two cases. The first was a patient with Hodgkin's disease, and the other a patient with acute T lymphoblastic leukemia. Bone marrow aspirates were performed while the patients were receiving recombinant human erythropoietin (rHu-EPO), 24 hours after the administration of vincristine, which was part of the therapeutic regimens. In all myeloaspirates over 90% of the numerous erythroblasts were in metaphasic arrest or displayed all the other aspects of so-called C mitoses, including star and ball metaphases, scattered chromosomes and multinuclear cells expressing so-called reconstructive polyproidism. All these alterations are caused by vincristine, a vinca dimer alkaloid, binding mechanistically to tubulin and thus blocking the polymerizing process that forms the mitotic spindle. The target cells for erythropoietin are specifically responsive cells, including microscopically identifiable erythroblasts. This is the first morphological demonstration in man of the combined effects of erythropoietin as a mitogen and vincristine as a mitotic blocker.