Mast Cell Leukemia-When a Nuclear Storm Explodes in the Human Body
Location
D.P. Culp Center Ballroom
Start Date
4-5-2024 9:00 AM
End Date
4-5-2024 11:30 AM
Poster Number
101
Name of Project's Faculty Sponsor
Kanishka Chakraborty
Faculty Sponsor's Department
Medical Oncology and Medicine, East Tennessee State University, Johnson City, TN
Competition Type
Competitive
Type
Poster Presentation
Presentation Category
Health
Abstract or Artist's Statement
Systemic mastocytosis (SM) is a rare myeloid disorder in which vasoactive mast cells infiltrate at least one systemic organ other than the skin. SM causes systemic symptoms, most commonly pruritus, flushing, diarrhea, nausea, vomiting, palpitations, and may cause anaphylaxis. It is a rare condition with unknown incidence, and it generally affects adults. Mast cell leukemia (MCL) is the rarest subtype of SM. It is defined by greater than 20% immature or atypical mast cells on bone marrow biopsy. MCL is seen in less than 5% of SM cases. A 71-year-old male presented to the emergency department after 6 months of nausea, vomiting, and diarrhea. The patient noted 60 pounds of weight loss over the same time period. Upon further questioning the patient noted generalized itching and sensation of palpitations. The patient underwent cholecystectomy and liver biopsy demonstrating atypical infiltration with myelomonocytic/histiocytic features and noted expression of CD117, CD68, CD45, and CD33. Expression of lymphoid markers was negative. Concern for systemic histiocytosis or bone marrow neoplasm was raised. Bone marrow biopsy was performed demonstrating CD117 proliferation of neoplasticism mast cells approximately 30%, with associated KIT D816V mutation; SRSF2 P95L mutation, and TET2 C1193*,N1753Kfs*3 mutations detected by next generation sequencing. A positron emission tomography (PET) scan was performed and demonstrated diffuse marrow activation, enlarged shotty mesenteric lymph nodes, and enlarged spleen. These diagnostic studies identified MCL and probable concurrent diagnosis of chronic monomyelocytic leukemia. The patient was initiated on prednisone taper and cromolyn sodium. Once the patient diagnosis was confirmed, the patient was initiated on avapritinib and referred to a higher level center for evaluation and possible clinical trial enrollment. SM is a broad diagnosis, further subcategorized into smoldering systemic mastocytosis (SSM), indolent systemic mastocytosis (ISM), aggressive systemic mastocytosis (ASM), SM-associated myeloid neoplasm (SM-AMN), and MCL. Each subcategory has a different risk profile. The WHO independent prognostic score uses five factors to assign a risk group including age greater than 60, hemoglobin less than 10, platelets less than 100000, one high risk mutation, and two or more high risk mutations (SRSF2, RUNX1, ASXL1). Low risk had significantly longer OS: a median of 12.2 years compared to high risk with a median OS of 1.9 years. Current treatment recommendations for patients with MCL include enrollment in a clinical trial, avapritinib, midostaurin, cladribine, and/or allogeneic hematopoietic stem cell transplantation. Avapritinib is a tyrosine kinase inhibitor and KIT inhibitor (directed at the D816V mutation). A recent pooled analysis of avapritinib therapy demonstrated greater survival and greater duration of treatment than best available therapy in comparison. The patient outlined in our case has poor risk factors associated with his disease, and data prior to the introduction of avapritinib demonstrate a dismal prognosis in patients with high-risk forms of SM. With the advent of the new therapy in this rare disease in the rarest subtype MCL, it is valuable to evaluate and record response to therapy.
Mast Cell Leukemia-When a Nuclear Storm Explodes in the Human Body
D.P. Culp Center Ballroom
Systemic mastocytosis (SM) is a rare myeloid disorder in which vasoactive mast cells infiltrate at least one systemic organ other than the skin. SM causes systemic symptoms, most commonly pruritus, flushing, diarrhea, nausea, vomiting, palpitations, and may cause anaphylaxis. It is a rare condition with unknown incidence, and it generally affects adults. Mast cell leukemia (MCL) is the rarest subtype of SM. It is defined by greater than 20% immature or atypical mast cells on bone marrow biopsy. MCL is seen in less than 5% of SM cases. A 71-year-old male presented to the emergency department after 6 months of nausea, vomiting, and diarrhea. The patient noted 60 pounds of weight loss over the same time period. Upon further questioning the patient noted generalized itching and sensation of palpitations. The patient underwent cholecystectomy and liver biopsy demonstrating atypical infiltration with myelomonocytic/histiocytic features and noted expression of CD117, CD68, CD45, and CD33. Expression of lymphoid markers was negative. Concern for systemic histiocytosis or bone marrow neoplasm was raised. Bone marrow biopsy was performed demonstrating CD117 proliferation of neoplasticism mast cells approximately 30%, with associated KIT D816V mutation; SRSF2 P95L mutation, and TET2 C1193*,N1753Kfs*3 mutations detected by next generation sequencing. A positron emission tomography (PET) scan was performed and demonstrated diffuse marrow activation, enlarged shotty mesenteric lymph nodes, and enlarged spleen. These diagnostic studies identified MCL and probable concurrent diagnosis of chronic monomyelocytic leukemia. The patient was initiated on prednisone taper and cromolyn sodium. Once the patient diagnosis was confirmed, the patient was initiated on avapritinib and referred to a higher level center for evaluation and possible clinical trial enrollment. SM is a broad diagnosis, further subcategorized into smoldering systemic mastocytosis (SSM), indolent systemic mastocytosis (ISM), aggressive systemic mastocytosis (ASM), SM-associated myeloid neoplasm (SM-AMN), and MCL. Each subcategory has a different risk profile. The WHO independent prognostic score uses five factors to assign a risk group including age greater than 60, hemoglobin less than 10, platelets less than 100000, one high risk mutation, and two or more high risk mutations (SRSF2, RUNX1, ASXL1). Low risk had significantly longer OS: a median of 12.2 years compared to high risk with a median OS of 1.9 years. Current treatment recommendations for patients with MCL include enrollment in a clinical trial, avapritinib, midostaurin, cladribine, and/or allogeneic hematopoietic stem cell transplantation. Avapritinib is a tyrosine kinase inhibitor and KIT inhibitor (directed at the D816V mutation). A recent pooled analysis of avapritinib therapy demonstrated greater survival and greater duration of treatment than best available therapy in comparison. The patient outlined in our case has poor risk factors associated with his disease, and data prior to the introduction of avapritinib demonstrate a dismal prognosis in patients with high-risk forms of SM. With the advent of the new therapy in this rare disease in the rarest subtype MCL, it is valuable to evaluate and record response to therapy.