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Thrombocytopenia after bone marrow transplantation for leukaemia: changes in megakaryocyte growth and
J A Adams1, A A Gordon, Y Z Jiang
1Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, Sutton, London.
Abstract:
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 19 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.
Insights
Following bone marrow transplantation (BMT), elevated megakaryocyte growth-promoting activity (MK-GPA) correlates with thrombocytopenia. Persisting low platelet counts after autologous BMT are linked to reduced megakaryocyte precursors.
Area of Science:
- Hematology
- Transplantation Immunology
- Oncology
Background:
- Thrombocytopenia is a common complication after bone marrow transplantation (BMT).
- Megakaryocyte growth-promoting activity (MK-GPA) is a key factor in platelet production.
Purpose of the Study:
- To investigate the correlation between MK-GPA and platelet recovery post-BMT.
- To explore the mechanisms underlying persistent thrombocytopenia after autologous BMT.
Main Methods:
- Serum MK-GPA levels were measured in 23 patients up to 120 days post-BMT.
- Platelet counts and transfusion requirements were monitored.
- Megakaryocyte production was assessed in marrow samples before and after autologous BMT.
Main Results:
- A close correlation was observed between MK-GPA levels and platelet counts.
- MK-GPA peaked before day 30 but remained elevated in patients with persistent thrombocytopenia.
- Megakaryocyte generation was reduced pre-BMT and absent post-autologous BMT in AML patients.
Conclusions:
- Thrombocytopenia post-BMT is associated with increased MK-GPA, reflecting reduced megakaryocyte pools.
- Persistent thrombocytopenia after autologous BMT in AML is attributed to decreased megakaryocyte precursors.