Discordant Response of Systemic Mastocytosis Associated With Myelodysplastic Syndrome After Midostaurin and Allogeneic Hematopoietic Stem-cell Transplantation

Systemic mastocytosis (SM) is a rare and heterogeneous disease characterized by the accumulation of neoplastic mast cells in various tissues, predominantly skin and bone marrow (BM). Thirty percent of SM is associated with a hematological neoplasm, referred to as SM-AHN, which confers a poor prognosis. The somatic KIT D816V mutation is a diagnostic hallmark of SM and the major therapeutic target in advanced mastocytosis. Here, we report the case of a patient with an SM associated with a myelodysplastic syndrome (MDS) who achieved discordant responses after midostaurin and allogenic hematopoietic stem cell transplantation (HSCT). We performed serial high throughput sequencing (HTS) to evaluate the responses after each line of treatment and to guide therapeutic decision making. Through these monitoring, we investigated the clonal evolution of this complex disease. A 59-year-old woman was referred to our Hematology department for night sweats, asthenia, weight loss, and a voluminous splenomegaly of 15 cm below the costal margin. Complete blood cell count revealed a pancytopenia (hemoglobin 7.6g/dL, platelets 60 10/L leukocytes 1.8 10/L with 0.6 10/L neutrophils) (Table 1-M0). The BM aspirate smear showed marked myelodysplastic changes in erythroid and granulocytic lineages, no ring sideroblasts, less than 5% of blasts and the presence of mast cells with abnormal cytological features: hypogranularity, oval eccentric nucleus, and spindle shape morphology (Fig. 1A). Mast cells showed a strong expression of CD25 and CD2 by flow cytometry. The BMbiopsy was infiltrated