Monocytosis in Systemic Mastocytosis: Clinico-Pathological and Prognostic Correlates.
Irina Maric, Olga Simakova, Nicolas Olivares, Safichia Chew, Dean D Metcalfe, Todd M Wilson. CC, NIH, Bethesda, MD; NIAID, NIH, Bethesda, MD
Background: A subset of patients with systemic mastocytosis (SM) have persistent peripheral blood monocytosis and fulfill WHO criteria for diagnosis of chronic myelomonocytic leukemia (CMML). CMML is aggressive disease with median survival of 20-40 months; however, clinico-pathological features and clinical course of SM patients with monocytosis are not well investigated.
Design: 179 patients with WHO defined SM were retrospectively analyzed. Diagnostic workup included physical examination, CBC, histopathologic, molecular and flow cytometric studies of bone marrow biopsies.
Results: Out of 179 SM patients, 11 (7%) displayed a persistent absolute monocyte count (AMC) over 1000/uL and fulfilled WHO criteria for SM-CMML. 4/11 patients had PB cytopenias in at least two lineages, and 7/11 had PB cytoses in at least two lineages (5/7 thrombocytosis, 5/7 neutrophilia, 4/7 eosinophilia and 4/7 lymphocytosis). All 11 patients carried point mutation at KIT codon 816 and were negative for FIP1L1-PDGFRa, BCR-ABL and JAK-2 mutations.
When we stratified patients according to the presence/absence of cytopenias, analysis showed that both groups had no statistically significant differences in mast cell burden as measured by serum tryptase levels (median 275 vs 343 ng/ml) or bone marrow biopsy involvement by mast cell aggregates (median 40% vs 45%). Both groups had similar bone marrow cellularity (median 90% vs 80%), no significant morphological evidence of myelodysplasia and less than 5% blasts. Patients with cytopenias had higher AMC (median 2.5 vs 1.1; p=0.04), no cytosis in any other lineages and no urticaria pigmentosa, but all had organomegaly. In contrast, 5/7 patients with cytoses had urticaria pigmentosa and 4/7 did not have organomegaly.
In all patients without cytopenias, PB counts (including AMC) remained stable over a median follow-up period of 12 years (range 2-25 years). No patients died of their disease and only 2 patients received cytoreductive treatment during the follow-up period. In contrast, 3/4 patients who presented with cytopenias required cytoreductive treatment and 2/4 died of disease over a median follow-up period of 3.5 years (range 0.5-5 years).
Conclusions: SM patients who present with monocytosis and no cytopenias have indolent disease course and usually do not require cytoreductive treatment. SM patients who present with monocytosis and cytopenias have more aggressive disease course with a prognosis similar to CMML. The occurrence of cytopenias may be a significant classification marker predicting disease severity and outcome in SM patients with monocytosis.
Monday, February 28, 2011 2:45 PM
Platform Session: Section B, Monday Afternoon