Influence of platelet count at diagnosis and during the course of disease on prognosis in MDS patients

Abstract

Thrombocytopenia at diagnosis and platelet drop within the first 6 months have an adverse effect on prognosis of MDS patients. We therefore were interested in the association and impact on prognosis of morphologic findings of megakaryocytes and platelets with platelet count at diagnosis, bleeding complications, and the drop of platelets during the course of disease. This retrospective analysis was based on 334 MDS patients from the Duesseldorf MDS registry that were followed up for blood counts, bleeding, transfusion dependency, and AML evolution and correlated with morphology of the megakaryocytes and platelets. Thrombocytopenia was found more frequently in higher risk MDS and was associated with hypocellularity of the megakaryocytes in the bone marrow. Signs of bleeding were present at diagnosis in 14% and occurred during the disease in 48% of all MDS patients. Death due to bleeding was ranked third behind infections and AML. A decrement of platelets during the first 6 months was associated with an inferior overall survival of 21 vs. 49 months and with a higher cumulative 2-year AML rate of 22.2% vs. 8.3% (p = 0.001). In a multivariate analysis, besides bone marrow blasts and karyotype, decreasing platelets were also associated with an inferior outcome. Signs of bleeding are present in a relevant number of MDS patients and account for significant morbidity and mortality in MDS. We could demonstrate the prognostic importance of decreasing platelets during the course of disease in all MDS patients, identifying patients at higher risk for death or AML progression.

Keywords: Bleeding; MDS; Morphology; Platelet drop; Prognosis; Thrombocytopenia.

Fig. 1

Overall survival according to initial platelet count. Cumulative survival probability according the to the initial platelet count. Patients with platelet counts between 50,000 and 100,000/µl, and with platelet counts < 50,000/µl had a significantly worse survival probability with medians of 33 and 31 months in comparison to a normal platelet count with 70 months OS (p = 0.003)

Fig. 2

Initial platelet count and platelets at landmark depending on outcome. Scatter plot of the initial platelet count and platelets at landmark for each patient depending on outcome (alive in blue and dead in red)

Fig. 3

Overall survival after landmark of 6 months. Cumulative survival of patients with and without a platelet decrement. A platelet decrement of at least 25% within the first 6 months (± 1 months) after diagnosis was significantly associated with an inferior survival of 21 vs. 49 months, respectively (p < 0.001)

Fig. 4

AML progression after landmark for all patients. Cumulative incidence of AML evolution in patients with and without platelet decrement. The 2-year cumulative incidence of AML evolution differed significantly between patients with decreasing platelets of at least 25% at landmark of 6 months and without decreasing platelets (8.3% vs. 22.2%, p < 0.001)

Fig. 5

Forest plot of HR for overall survival (a) and AML evolution (b). a Significant predictors for survival were age > 65 years, a medullary blast count > 5%, a high-risk karyotype, and platelet drop > 25% within 6 months after diagnosis. b In a cause-specific hazard risk model for AML progression, platelet drop, a medullary blast count > 5%, and a high-risk karyotype were significantly correlated with AML evolution