A phase I trial of recombinant human thrombopoietin in patients with delayed platelet recovery after hematopoietic stem cell transplantation

Delayed platelet recovery is a significant complication after both autologo us and allogeneic hematopoietic stem cell transplantation (HSCT). A multice nter, phase I dose-escalation study of recombinant human thrombopoietin (rh TPO) was conducted to assess its safety and to obtain preliminary data on i ts efficacy in patients with persistent severe thrombocytopenia (<20,000/<m u>L) >35 days after HSCT. Thirty-eight patients, 37 of whom were evaluable, were enrolled in the study from April 1996 through January 1997. rhTPO was administered at doses of 0.6, 1.2, and 2.4 mug/kg as a single dose (group A) or in multiple doses every 3 days for a total of 5 doses (group B). No s ignificant adverse effects were observed. Ten patients had recovery of plat elet counts during the 28-day study period; 3 of these 10 had an increase i n marrow megakaryocyte content 7 days after completing treatment with rhTPO . When all baseline marrows were compared with samples after rhTPO treatmen t, there was no difference in marrow megakaryocyte content (P = 0.49). This study design could not answer the question of whether the recoveries of pl atelet counts observed in some patients were spontaneous or influenced by r hTPO treatment; nonetheless, the authors found no correlation between the d ose of rhTPO and the recovery of platelet counts. Increases in serum TPO le vels were dose-dependent and remained significantly elevated for up to 72 h ours after treatment. To evaluate response, further studies of treatment st rategies with rhTPO in patients with delayed platelet recovery are required .