Platelet secretion defect in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL-5).

similar to that reported by Falini, and was associated with a higher proportion of normal karyotype (93% vs 60%; P .001), lower leukocyte count at diagnosis (32 109/L vs 69 109/L; P .01), and lower bone marrow infiltration (51% vs 72% blast cells, P .001). Interestingly, the frequency of NPM1 and FLT3 internal tandem duplication (FLT3-ITD) mutations did not differ between patients with and without MLD (59% vs 50%, and 31% vs 38%, respectively). NPM1 mutations were found in 68 patients (52%). MLD was observed in 19 patients (28%) with mutated NPM1 and in 13 (21%) with wild-type NPM1. Outcomes in patients with mutated NPM1 were similar for those with and without MLD; response rate was 95% and 85%, 5-year relapse incidence was 35% 26% and 47% 16%, and 5-year survival was 56% 23% and 46% 14%, respectively. In contrast in patients with wildtype NPM1, those patients with MLD showed an inferior response rate to induction chemotherapy (53% vs 85%; P .02). When the analysis was restricted to younger patients ( 60 years) those with MLD showed a lower 5-year survival (0% vs 40% 16%, P .012; Figure 1). The unfavorable prognostic value of MLD on response rate (P .034; relative risk, 4.8; 95% confidence interval, 1.1-20) and survival (P .036; hazard ratio 2.5; 95% confidence interval, 1.1-6) was confirmed in a multivariate analysis. These results confirm that, although dysplastic features are a common trait in NPM1-mutated AML, they do not confer a worse prognosis. Falini et al found that gene expression profiling did not identify any distinctive MLD-associated gene signature in the mutated NPM1 cohort.6 The correlation found in the present study between an unfavorable outcome and dysplastic features in wildtype NPM1 IR-AML patients leads us to suggest that a search for novel genetic or epigenetic markers in this AML subgroup might reveal a specific biologic identity. In conclusion, the prognostic relevance of MLD in IR-AML might be dependent on NPM1 mutational status. Whereas MLD predicts an adverse outcome in patients with wild-type NPM1, it lacks prognostic value in NPM1-mutated AML. Nonetheless, this observation requires further confirmation in a larger series of patients.