Baylor University Medical Center Proceedings January 2014, Volume 27, Number 1 | Página 24

Systemic mastocytosis with associated acute myelogenous leukemia Leah Zhrebker, MD, Barry Cooper, MD, and John R. Krause, MD Systemic mastocytosis (SM) is a condition associated with a clonal neoplastic proliferation of mast cells. Approximately 40% of patients with SM present with an associated clonal hematological non–mast cell lineage disorder. Patients presenting with SM–acute myeloid leukemia (AML) have the worst prognosis. We present a case of a 62-year-old woman who was diagnosed with SM-AML. After initial treatment with a standard regimen of cytosine arabinoside (Ara-C)/idarubicin, her bone marrow showed residual blasts. She was subsequently treated with a second induction regimen of clofarabine and high-dose Ara-C, which resulted in remission of AML, although a residual mast cell infiltrate persisted in her bone marrow. After consolidation therapy with clofarabine/Ara-C, the patient received a stem cell allograft. A follow-up bone marrow showed no residual blasts but persistent mast cells occupying about 5% of the marrow volume. astocytosis is a clonal neoplastic proliferation of mast cells that accumulate in one or more organ systems. According to the latest classification from the World Health Organization, there are seven subtypes of mastocytosis (1). The second most common type of mastocytosis is known as systemic mastocytosis with an associated clonal hematologic non–mast cell lineage disorder (SMAHNMD). These non–mast cell lineage disorders may include myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), chronic myelogenous leukemia, MDS/MPN, plasma cell myeloma, non-Hodgkin lymphoma, and unclassifiable myelogenous malignancy (2). An associated AML has the worst prognosis (3). We present a case of mastocytosis associated with an AML and discuss the pathology and treatment. M PATIENT DESCRIPTION A 62-year-old white woman was noted to have a pancytopenia 3 years prior to admission. Her hematocrit was 30%, white blood cell count 3300 K/uL with 44% neutrophils, and platelet count 109,000 K/uL. Bone marrow biopsy revealed trilinear maturation without an abnormal infiltrate and normal cytogenetics and flow cytometry. Her spleen was enlarged, and the liver was infiltrated by adipose tissue. Her body mass index was 25.1 kg/m2. She was believed to have steatohepatitis with pancytopenia secondary to hypersplenism. 22 Two years later, her pancytopenia and splenomegaly were unchanged. She now had fatigue, dyspnea, and fever (99°F) for 2 weeks. Her white blood cell count was 63,000/mm3 with 38% circulating blasts, hematocrit 27%, and platelets 57,000/mm3. A bone marrow biopsy showed 50% infiltration with mast cells and 50% myeloblasts, confirming the entity of SM-AHNMD (Figure 1). Results of an AML fluorescent in situ hybridization panel and routine cytogenetics were negative. She had a C-KIT D816V mutation but no JAK-2 mutation. Her serum tryptase level was 189 ng/mL (normal level, <11.4). The patient was admitted to the hospital and underwent induction chemotherapy with cytosine arabinoside (Ara-C) (100 mg/m2/day by continuous infusion for 7 days) and idarubicin (12 mg/m2/day for 3 days). She was also started on dasatinib at 100 mg orally daily. Bone marrow biopsy 14 days after induction of treatment revealed persistent myeloblasts and mast cell infiltrate requiring a second course of therapy with 5 days of high-dose Ara-C (1 g/m2/day) and clofarabine (40 mg/ m2/day). Because of the persistent mast cell infiltrate, dasatinib was discontinued. Her blood counts recovered on discharge, except for a platelet count of 40,000 K/uL. Her white blood cell count was 8,900 K/uL, and her hematocrit was 32.2%. Repeat bone marrow biopsy showed no residual myeloblasts, with residual mast cells of 15%. Her tryptase level decreased to 77 ng/mL. She was readmitted 3 weeks later for consolidation chemotherapy with clofarabine/Ara-C. Four weeks later she had a stem cell allograft using an unrelated donor with a preparative regimen of busulfan and cyclophosphamide. Follow-up marrow revealed no evidence of AML, 5% residual mast cell infiltrate, and focal increased reticular fibrosis. DISCUSSION The diagnosis of SM-AHNMD may be difficult to establish, as the histologic and cytologic features of systemic mastocytosis From the Department of Hematology/Oncology (Zhrebker, Cooper) and the Department of Pathology, Section of Hematopathology (Krause), Baylor University Medical Center at Dallas and the Baylor Charles A. Sammons Cancer Center at Dallas. Corresponding author: Leah Zhrebker, MD, Department of Hematology/Oncology, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2014;27(1):22–24