Systemic mastocytosis associated with acute myeloid leukemia

Abstract

Dear Editor, Systemic mastocytosis (SM) is a heterogeneous group of rare diseases characterized by the proliferation of neoplastic mast cells that almost always involves bone marrow [1]. Here, we describe an unusual case of SM associated with acute myeloid leukemia. A previously healthy 42-year-old male was admitted to the emergency department complaining of fatigue, weight loss, and easy bruising which had started 2 weeks before. The physical exam was unremarkable, except for skin pallor and some ecchymosis. Blood counts showed Hb 77 g/L, platelets 6.0 × 10/L, and WBC 4.74 × 10/L, with 59% blasts. Liver and kidney function tests were within the normal range. He had no history of allergic reaction. The bone marrow smear showed 49% blasts with large Auer rods. Furthermore, there were 35% hypergranulated cells; the majority of them exhibited a bilobed nucleus with condensed chromatin consistent with atypical mast cell type II. In the immunophenotypic analysis, blasts were positive for CD34, HLA-DR, CD33, and CD117 and negative for CD56. Mast cells were CD45+/CD33+/CD117. CD2 and CD25 were aberrantly expressed. Conventional cytogenetic analysis yielded a 46,XY,t(8;21)(q22;q22) karyotype. Molecular analysis revealed the presence of the RUNX1-RUNX1T1 transcript and also the D816V c-KIT mutation. The FLT3-ITD mutation was negative. A biopsy was performed and showed 50% cellularity with proliferated CD34-positive cells and also tryptase-positive mastocyte aggregates (Fig. 1). A diagnosis of systemic mastocytosis (SM) associated with acute myeloid leukemia (AML) was established. Therapy with “7 + 3” was initiated and he attained remission from AML, although still maintaining 15% mastocytes in the bone marrow smear. The serum tryptase level was also measured at this time, yielding a result above 200 μg/L, reflecting the mast cell burden. He received two cycles of high-dose cytarabine (3 g/m) for consolidation, but relapsed 3 months after. There are five subtypes of SM with different mast cell burdens (B-findings) and end organ damages (C-findings), highlighting the marked clinical heterogeneity within this disease. Appropriate diagnosis and assignment of specific subtypes require an integrated clinical and laboratorial approach, but can be puzzling, even with optimal assessment. This patient had more than 20% of bone marrow mast cells, so the mastocyte component of his disease is also consistent with mast cell leukemia, aleukemic variant. As in this case, SM can be associated with other hematologic neoplasms and there is evidence that both can be derived from a common progenitor [2, 3]. SM therapy should be individualized. Symptomatic medication can be used to control manifestations related to mast cell degranulation. Cytoreductive drugs like cladribine and hydroxyurea are often use to control mast cell proliferation [4]. D816V mutation of c-KIT is found in more than 80% of cases and is associated with resistance to imatinib [5, 6]. Midostaurin has recently been FDA-approved based on promising clinical results [7]. AML with t(8;21)(q22;q22) has usually a favorable prognosis, but this seems not to be the case when associated with systemic mastocytosis. Interestingly, c-KIT mutations, a hallmark of SM, have also been associated with inferior results in core binding factor leukemias [8, 9].