Excess mortality in the myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are the commonest hematologic malignancies in the elderly. Since many patients with MDS actually die from age-related ailments, the very disease burden of MDS remains largely unknown. This registry-based study was aimed at investigating the excess mortality attributable to MDS. We analyzed 7,408 adult patients diagnosed with primary MDS from 1980 to 2014. Excess mortality was estimated by comparing the patients' survival with that expected in the matched general population. Median age of patients was 74 years, 58% were males, and 65% belonged to the lower risk categories of the Revised International Prognostic Scoring System (IPSS-R). Excess mortality accounted for three-fourths of the all-cause mortality and was mainly driven by factors unrelated to leukemic transformation. Excess mortality increased with the IPSS-R risk category [Incidence rate ratio (IRR): 2.1, 95% CI: 1.9-2.3; P < .001]. Older age and male sex retained an independent association with higher excess mortality after discounting demographic effects. Excess mortality increased in the most recent periods just in the higher risk IPSS-R categories (IRR: 1.2; 95% CI: 1.1-1.3 when comparing periods 2007-14, 2000-06, and 1980-99). In conclusion, MDS carry a significant excess mortality, even in the lower risk categories, that is mainly driven by factors unrelated to leukemic transformation, and increases with older age, male sex, and poorer risk categories. Excess mortality has increased in recent years in the higher risk patients, which might be ascribed to a parallel increase in age-related comorbidities. Our results claim for more comprehensive treatment strategies for patients with MDS. Am. J. Hematol. 92:149-154, 2017. © 2016 Wiley Periodicals, Inc.

Incidence and characteristics of CD4(+)/HLA DRhi dendritic cell malignancies.

BACKGROUND AND OBJECTIVES: Recent reports suggest that CD4(+)/CD56(+)/lineage(-) hematopoietic neoplasias are aggressive types of malignancies involving lymphoplasmacytoid/DC2 dendritic cells (DC). Here, we report on the incidence of DC malignancies and their clinical, biological, phenotypic and cytogenetic characteristics. DESIGN AND METHODS: From a large series of 392 patients with acute myeloblastic leukemia (AML) and 739 with non-Hodgkin's lymphoma (NHL), five cases (three presenting as acute leukemia and two as NHL) showed clinical, morphologic and phenotypic features compatible with a DC malignancy. RESULTS: The overall incidence of DC malignancies among all AML and NHL cases was 0.76% and 0.27%, respectively. At presentation, these patients displayed cutaneous nodules, splenomegaly and lymph node involvement with variable levels of peripheral blood (PB) and/or bone marrow (BM) infiltration in association with anemia and thrombocytopenia. Cytologic studies showed immature appearing blast cells with negative cytochemistry reactions for both myeloperoxidase and esterases. A highly suggestive DC phenotype based on co-expression of CD123(hi)/HLADR(+)/lin(-)/CD56(+)/CD45(dim) associated with a germline configuration of both the IgH and TCRgamma genes was found in all except one patient who was CD56(-). Expression of other markers compatible with a DC origin was found in all cases. INTERPRETATION AND CONCLUSIONS: We show that DC-derived malignancies can present as either cutaneous lymphoma or acute leukemia, although their incidence is extremely low (<< >1%). While most of these DC neoplasias probably correspond to the malignant counterpart of DC2/lymphoplasmacytoid DC, neoplasias of myeloid DC might also exist, chemotherapy followed by consolidation with ASCT is apparently the most effective strategy for achieving a durable remission in these individuals.