Thrombocytopenia after bone marrow transplantation for leukaemia: changes in megakaryocyte growth and growth‐promoting activity

Megakaryocyte growth‐promoting activity (MK‐GPA) was scored on a scale of 0‐3 in the serum of 23 patients up to 120 d following bone marrow transplantation (BMT) for leukaemia. Nine of] 9 allografts and two of four autografts had thrombocytopenia requiring platelet transfusion more than 30 d after BMT. There was a close correlation between MK‐GPA and platelet count. MK‐GPA reached a maximum before day 30 after BMT but remained elevated in patients with persisting thrombocytopenia secondary to poor engraftment, graft‐versus‐host disease (GVHD) or relapse. Recent platelet transfusion did not suppress serum MK‐GPA. Two of four patients undergoing autologous BMT for acute myeloid leukaemia (AML) showed delayed platelet recovery and persistence of MK‐GPA in the serum. Seven further AML remission marrows were tested for megakaryocyte production before or after autologous BMT, using pooled sera with known MK‐GPA activity. Megakaryocyte generation was reduced before BMT and absent in post transplant samples. This failure of MK production was not corrected by T‐cell depletion or by the presence of adherent cells from normal marrow. We conclude that thrombocytopenia after BMT is associated with an appropriate increase in MK‐GPA levels in response to a reduction in the megakaryocyte pool rather than the platelet pool, and that persisting thrombocytopenia after autologous BMT is due to decreased numbers of available megakaryocyte precursors.