Sigurd Broesby-Olsen1, Thomas Kristensen2, Hanne Vestergaard3, Kim Brixen4, Michael Boe Møller5, Carsten Bindslev-Jensen6. 1. Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: sigurd.broesby-olsen@ouh.regionsyddanmark.dk. 2. Department of Pathology, Odense University Hospital, Odense, Denmark. 3. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Hematology, Odense University Hospital, Odense, Denmark. 4. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Endocrinology, Odense University Hospital, Odense, Denmark. 5. Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense University Hospital, Odense, Denmark. 6. Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Abstract
BACKGROUND: Clinical manifestations of indolent systemic mastocytosis (ISM) comprise mediator-related symptoms, anaphylaxis, and osteoporosis. A new sensitive method for KIT D816V mutation detection allows quantification of the level of mutation-positive cells. OBJECTIVE: To investigate whether the fraction of KIT D816V positive cells in peripheral blood (PB) or bone marrow (BM) aspirate in adult patients with ISM correlates with clinical manifestations of the disease. METHODS: We included 48 adult patients with ISM (28 females/20 males) from our center in whom the KIT D816V mutation level in both BM aspirate and PB was analyzed. For each patient, the severity of mediator-related symptoms (skin, gastrointestinal, musculoskeletal, and neuropsychiatric) and episodes of anaphylaxis were evaluated by interview and medical record files. Bone mineral density was determined by using dual-energy x-ray absorptiometry. RESULTS: Median fraction (range) of KIT D816V positive cells was 0.6 (0.01%-90%) in BM and 0.3 (0.003%-49%) in PB. Mutation level did not differ between patients with none/mild symptoms and patients with moderate/severe symptoms, patients with and without anaphylaxis, or patients with osteoporosis/osteopenia and normal bone mineral density. No significant differences in clinical profile were detected in patients with different levels of mutation except for an indication of longer disease duration and age in patients with highest mutation levels. CONCLUSION: To our knowledge, this is the first report on the clinical impact of the fraction of KIT D816V mutation positive cells in ISM, which in the present study does not seem to correlate with clinical manifestations of the disease.
BACKGROUND: Clinical manifestations of indolent systemic mastocytosis (ISM) comprise mediator-related symptoms, anaphylaxis, and osteoporosis. A new sensitive method for KITD816V mutation detection allows quantification of the level of mutation-positive cells. OBJECTIVE: To investigate whether the fraction of KITD816V positive cells in peripheral blood (PB) or bone marrow (BM) aspirate in adult patients with ISM correlates with clinical manifestations of the disease. METHODS: We included 48 adult patients with ISM (28 females/20 males) from our center in whom the KITD816V mutation level in both BM aspirate and PB was analyzed. For each patient, the severity of mediator-related symptoms (skin, gastrointestinal, musculoskeletal, and neuropsychiatric) and episodes of anaphylaxis were evaluated by interview and medical record files. Bone mineral density was determined by using dual-energy x-ray absorptiometry. RESULTS: Median fraction (range) of KITD816V positive cells was 0.6 (0.01%-90%) in BM and 0.3 (0.003%-49%) in PB. Mutation level did not differ between patients with none/mild symptoms and patients with moderate/severe symptoms, patients with and without anaphylaxis, or patients with osteoporosis/osteopenia and normal bone mineral density. No significant differences in clinical profile were detected in patients with different levels of mutation except for an indication of longer disease duration and age in patients with highest mutation levels. CONCLUSION: To our knowledge, this is the first report on the clinical impact of the fraction of KITD816V mutation positive cells in ISM, which in the present study does not seem to correlate with clinical manifestations of the disease.
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