Abstract
Abstract 5052
Introduction:
Systemic mastocytosis(SM) is diagnosed when clonal, neoplastic mast cells are demonstrated in extracutaneous tissues. SM is a heterogeneous disorder ranging from indolent disease to aggressive multisystem involvement. We have an established mastocytosis working group in our Trust which was registered with the European Competence Network of Mastocytosis(ECNM) in 2005. We present data prospectively collected using an ECNM algorithm for the management of SM patients over 5 years.
Methods:
120 cases of cutaneous mastocytosis have been discussed at 3 monthly multidisciplinary meetings with dermatology colleagues. Full blood counts, liver, bone profile and DEXA scans are reviewed with clinical symptoms and treatments. Patients with a tryptase level of >20ng/ml are offered haematology review and bone marrow investigation. In addition patients referred directly to haematology for a second opinion have their cases and bone marrows reviewed. Bone marrow samples are sent for c-kit D816V mutation analysis.
Results:
Classification of SM patients. 59/120 (46%) patients were offered bone marrow biopsies. Tryptase levels for these ranged from 15.1–760ng/ml (median 51.5ng/ml).4 patients declined biopsy.5/55 had normal biopsies and were c-kit negative.50 patients had SM.47/50(94%) met the WHO major criteria and 3/50(6%) minor criteria. These were subclassified-38/50(76%) had Indolent Systemic Mastocytosis(ISM);1/50 (2%) had Smouldering Systemic Mastocytosis(SSM);5/50(10%) had Aggressive Systemic Mastocytosis and 6/50(12%) had Systemic Mastocytosis with associated haematologiocal non-mast cell lineage disorder(SM-AHNMD). The bone marrow trephine disease burden was variable:ASM (range 5–100%), SSM 20%, ISM (5-45%) and AHNMD (5-100%). Tryptase levels reflected total disease bulk including cutaneous burden. C-KIT D816V mutation 44 patients with SM had samples analysed for the D816V mutation. 35 were positive (80%) and 9 negative (20%). Clinical Symptoms: 11/59 (19%) patients were asymptomatic (10 had ISM and 1 SSM).36/59 (61%) patients had urticarial symptoms needing symptomatic treatment (2 normal marrow, 2 AHNMD, 2 ASM and 30 ISM).16/59 (27%) patients had allergic symptoms ranging from mild allergies to anaphylaxis.(3 normal marrows, 13 ISM).13/59(22%) had gastrointestinal symptoms ranging from loose motions to severe colitis(1 normal marrow,1 ASM and 11 ISM). DEXA results:36/59(61%) patients had reported DEXA scans at our Trust, the rest reviewed locally. 6/36 (16%) had osteoporosis and required treatment. One 63yr old female patient has SM-AHNMD(MPD). 5 patients had ISM. 3 were females (age range 45–65yrs; tryptase levels 42.9, 49.1 and 60.5ng/ml)) and 2 male (both 45yrs: tryptase levels 31.2 and 47.8ng/ml). After 1 year of treatment with bisphophonates one of the male patients showed an improvement in his osteoporosis indices.7/36(19%) had osteopaenia reported all with a diagnosis of ISM.5 were male and 2 female (tryptase range 21.1–174ng/ml:median 40.3ng/ml).23/36(64%) patients had normal DEXA scans.
Management:
Treatment regimes in patients with SM are for symptom control. Antihistamines, anti-inflammatory agents, anti-leucotriene agents, mast cells stabilising agents, bisphosphonates and steroids are used. In severe anaphylactic patients self administration of adrenaline is taught. Patients with ASM have been treated with various modalities e.g. Cladrabine, Alpha Interferon, Dasatinib, Imatinib (D816V negative patients) and Midostaurine with variable partial responses.2 patients with ASM have died due to rapidly progressive disease.2 AHNMD patients have an associated MPD (1 Jak 2 postive) and are being treated with pegylated alpha interferon and venesection.2 AHNMD patients died as a result progressive acute myeloid leukaemia and Non Hodgkins Lymphoma.2 AHNMD patients (MDS/MGUS) are being monitored.
Conclusions:
Our data reflects the heterogeneous nature of this disorder both clinically and in the histological classification. Patients with ISM can have severe clinical manifestations and treatment needs to be tailored to the individual's symptoms. Assessment and surveillence for osteoporosis is vital for all patients. ASM patients have limited treatment options with variable and unsustained responses. Further development of evidence based novel therapies requires multicentred trials in this rare group of patients.
Disclosures:
Harrison: Incyte: Honoraria; Novartis: Honoraria.
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