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 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.
Adams
J A
JA
Department of Haematology, Royal Postgraduate Medical School, Hammersmith Hospital, Sutton, London.
Gordon
A A
AA
Jiang
Y Z
YZ
Macdonald
D
D
McCarthy
D M
DM
Zuiable
A
A
Treleaven
J
J
Powles
R L
RL
Barrett
A J
AJ
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007938:Leukemia / Q000601:surgery*; D008297:Male; D008533:Megakaryocytes / Q000473:pathology*; D008562:Membrane Glycoproteins; D000090204:Mesothelin; D008875:Middle Aged; D010976:Platelet Count; D011184:Postoperative Period; D011506:Proteins / Q000032:analysis*; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology* / Q000473:pathology
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D000090204:Mesothelin