Report a clinical case of Advanced Systemic Mastocytosis Associated with Hematological Neoplasia (MAS-ANH) under treatment with the AZAVIT-ABCDEF protocol, 7 days every 28 days (azacytidine associated with high doses of vitamins B1, C, and D, with erythropoietin and filgrastim). Brazil Platform CAAE: 53015421.0.0000.5463. After obtaining informed consent.

Assessment of patient's information from HSPE's computer-based patient records.

A 71-year-old male with fatigue, diarrhea, pruritus, and extensive skin lesions in the groin, lymph node enlargement, and splenomegaly. Hb = 8.2 g/dL, platelets = 64,000/mm3, and leukocytes = 11.38 thousand/mm3 (1/5/54/0/0/37/3), Alkaline phosphatase = 239 U/L (30-120 U/L). Myelogram showed dysplastic changes, 4% blasts, and moderate mastocytosis. Bone marrow biopsy revealed 60% cellularity and mastocytosis. Immunohistochemistry: CD117 (+). Lymph node and skin biopsy showed infiltration by mast cells. Bone scintigraphy showed increased uptake in the skull, pelvis, spine, and femurs. Initially treated with alpha interferon, which resulted in increased cytopenias and worsening of constitutional symptoms. Decided to start zoledronic acid and AZAVIT-ABCDEF protocol, receiving 27 cycles every 28 days. Showed improvement in hemogram with sporadic blood component transfusions and reduction in splenomegaly. Pruritus and diarrhea improved significantly, and the patient gained weight. Triptase level still at 145 μg/mL (normal = 11 μg/mL) with slight improvement in skin lesions. Current blood count: Hb = 10.8 g/dL, platelets = 71,000/mm3, and leukocytes = 9.280/mm3 (1/5/59/1/0/14/20).

MAS-ANH is a rare entity associated with a mutation in the KIT D816V gene that encodes the receptor for stem cell factor (CD117). Additional mutations are commonly found, such as TET2 (29%), ASXL1 (17%), and CBL (11%). The main manifestations are hematological and gastrointestinal disturbances. Other symptoms include pruritus, urticaria, skin infiltration, bone pain, fatigue, fever, headache, and anaphylactic reactions. A prognostic index showed worse outcomes for cases with age > 60 years, thrombocytopenia, anemia, elevated alkaline phosphatase, and the presence of adverse mutations (ASXL1, RUNX1, and NRAS). Treatment options include KIT gene inhibitors (midostaurin, imatinib, and avapritinib), alpha interferon, and 2-CDA, with short-lived responses and the possibility of worsening cytopenias. Antihistamines and corticosteroids are used symptomatically. The good hematological response observed in this case probably occurred due to the presence of hematological clonal abnormalities resembling myelodysplastic neoplasia without mastocytosis. We believe that the protocol promotes differentiation by increasing the transcription of factors related to cell differentiation and improving aerobic metabolism.

MAS-ANH is an aggressive pathology with a median survival of 20 months, even with the use of KIT gene loop inhibitors. At diagnosis, the patient presented with 4 out of 5 poor prognostic features and has already achieved a survival of 41 months. Further studies will be required to confirm the improvement in quality of life and survival with the AZAVIT-ABCDEF protocol.