Hydroxyurea-induced marked oscillations of platelet counts in patients with polycythemia vera

Two prospectively studied patients with polycythemia vera (PV)whose platele t counts showed marked periodic fluctuation during treatment with hydroxyur ea (HU) are reported. Cycle lengths in both were approximately 28 to 30 day s. In one patient, the cyclic process was no longer evident when treatment with HU was withheld, and it reappeared on treatment rechallenge. Circulati ng thrombopoietin (TPO) levels fluctuated out of phase with the platelet co unt despite markedly reduced TPO-receptor (c-Mpl) expression in bone marrow megakaryocytes. These observations suggest that the cyclic phenomenon may be related to both a transient state of HU-induced depletion of megakaryocy tes and a concentration-dependent mitigation by TPO of the HU effect on meg akaryocytes and their precursors. It is conceivable that the affected patie nts harbor a megakaryocyte progenitor pool whose apoptotic activity is diff erently modulated by either HU or high concentrations of TPO. (Blood, 2000; 96:1582-1584) (C) 2000 by The American Society of Hematology.