Hyperfibrinolysis in a case of myelodysplastic syndrome with leukemic spread of mast cells

Mast cells (MC) are multipotent hemopoietic effector cells producing divers e mediators like histamine, heparin, or tissue type plasminogen activator. We report a 75-year-old male patient with myelodysplastic syndrome (MDS) of recent onset (3 months' history) associated with a massive leukemic spread of immature tryptase(+) MC (tentative term: myelomastocytic leukemia). The patient presented with pancytopenia, bleeding, hypofibrinogenemia, and an increased cellular tryptase level. Moreover, an excessive elevation of plas min-antiplasmin complexes (9,200 ng/ml; normal range: 10-150), an elevated D-dimer, and an increase in thrombin-antithrombin III complexes were found. The identity of the circulating MC was confirmed by immunophenotyping (CD1 17/c-kit(+), CD123/IL-3R alpha(-), CD11b/C3biR(-)), biochemical analysis (c ellular ratio I:ng:ngl of tryptase to histamine >1), and electron microscop y. Bone marrow (bm) examination showed trilineage dysplasia (17% blasts), 3 0% diffusely scattered MC, and a complex karyotype. No dense, compact MC in filtrates (mastocytosis) were detectable in bm sections. Despite hyperfibri nolysis and mediator syndrome (flushing, headache), the patient received re mission induction polychemotherapy (DAV) followed by two cycles of consolid ation with intermediate dose ARA-C (2 x 1 g/m(2)/day on days 1, 3, and 5). He entered complete remission after the first chemotherapy cycle without ev idence of recurring MDS. Moreover, in response to chemotherapy, the hyperfi brinolysis and mediator syndrome resolved, and the circulating c-kit(+) MC disappeared. We suggest consideration of polychemotherapy as a therapeutic option in patients with high-risk MDS of recent onset, even in the case of MC lineage involvement. (C) 1999 Wiley-Liss, Inc.