Prolonged isolated thrombocytopenia after hematopoietic stem cell transplantation: morphologic correlation

Prolonged isolated thrombocytopenia, defined as recovery of other cell coun ts with continuous dependence on platelet transfusions for greater than 90 days after hematopoietic stem cell transplantation (HSCT), develops in appr oximately 5% of patients who undergo HSCT, Although the clinical conditions associated with prolonged isolated thrombocytopenia have been studied, a s ystematic review of bone marrow biopsies has not been performed and the pat hophysiologic basis has not been defined. We reviewed all HSCT at one cente r from 1990 to 1995 (n = 454) and found 12 cases that met criteria for prol onged isolated thrombocytopenia (incidence = 12/454 or 3%), Bone marrow cor e biopsies from 12 patients with prolonged isolated thrombocytopenia were r eviewed to determine cellularity, numbers of megakaryocytes, the presence o f atypical forms, and clusters of megakaryocytes, These marrow megakaryocyt e counts were compared to age and disease matched controls, and 11 normal d onors. Patients (aged 1-56 Sears, mean 32 years) who underwent HSCT (four s ibling HLA-identical, five autologous bone marrow, three autologous periphe ral stem cell) with prolonged isolated thrombocytopenia had a statistically significant lower absolute megakaryocyte count in bone marrow biopsies per formed before transplantation and more than 30 days after transplantation c ompared to control patients (aged 4 months to 50 years, mean 31 years) who underwent HSCT (four sibling HLA-identical, four autologous bone marrow, fo ur autologous peripheral stem cell) for similar conditions. No apparent dif ferences were seen in size of megakaryocytes, nuclear-cytoplasmic ratios, o r clustering of megakaryocytes, Overall marrow cellularities were similar i n the three groups, These findings suggest that decreased differentiation o f megakaryocytes from stem cells, rather than ineffective platelet producti on or peripheral destruction of platelets, causes prolonged isolated thromb ocytopenia in HSCT patients. Low megakaryocyte counts prior to HSCT may be a useful prognostic indicator, as this feature was associated with the deve lopment of prolonged isolated thrombocytopenia.