CD30/CD123 Expression in Systemic Mastocytosis Does Not Correlate with Aggressive Disease

Abstract

AbstractAbstract 1746 Introduction:Systemic Mastocytosis (SM) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical manifestations and limited treatment options for patients with aggressive disease. The WHO Classification sub divides SM patients into Indolent (ISM: evidence of clonal mast cells in bone marrow), Smouldering (SSM: Trypstase > 200ng/ml;organomegaly without dysfunction; bone marrow mast cell burden > 30% ), Aggressive (ASM: organomegaly with laboratory evidence of dysfunction), Mast Cell Leukaemia (MCL; > 20% mast cells on aspirate and >10% on blood film) and Associated Haematological Non-Mast Cell Disorders (AHNMD). The c-kit mutation (D816V) is present in > 90% of SM patients. Tryptase levels reflect total mast cell burden. To date there is no discriminatory marker to allow for identification of SM patients with more aggressive disease. CD30 (Ki-I antigen) has been reported as a potential marker for mast cells in high grade mastocytosis (Sotlar et al, 2011).We present preliminary data on 43 SM patients seen at Guys and St Thomas’ Hospitals NHS Foundation Trust looking at CD30 and CD123 expression with clinical correlates. Methodology:43/58 SM patients who have a full set of clinical records and bone marrow trephine samples have been evaluated. Bone marrow trephine processing: fixation in a neutral buffered formalin < 24hours; EDTA decalcification for 48 hours;Immunochemistry on an automated immunostainer (Leica Bondmax)using standard protocols: CD 30 (Dako dilution 1:75, antigen retrieval ER2). CD123 (BD Sciences, Novacastra, dilution 1:400,antigen retrieval ER2). Bone Marrow trephine samples were reviewed by haematopathologists at diagnostic MDM. Disease bulk was estimated as a percentage of the trephine sample. Immunocytochemistry review of the CD30/CD123 was reviewed by a single haematopathologist for this study. Clinical information was reviewed for laboratory results, tryptase levels, clinical symptoms and SM diagnosis. Results:43 patients: M:F(18:25). SM diagnoses: 26 ISM (60%), 2 SSM (5%),3 ASM (7% ), 12 AHNMD (28%). Data on 43 patients for CD30 expression and 40 for CD123 expression.Tryptase: 20 CD30(+) patients median 74.9ng/ml (range 16.6–285ng/ml): 23 CD 30(−) patients median 43.6ng/ml (range 15.1–386ng/ml).Table 1SM diagnosis and CD30 expressionDiagnosisTotalCD30 +CD30 -Indolent SMISM2610/30%16/70%SSM22/100%0Aggressive SMASM32/66%1/33%AHNMD126/50%6/50%Table 2:CD123 expression and SM classificationCD123+CD123-ISM4/40%19/63%SSM2/20%0ASM1/10%2/7%AHNMD3/30%9/30%Total1030Dual CD30/CD123 positive: 8/40 patients: 2 ISM / / 3 AHNMD.Table 3:Disease bulk on trephine and CD30 expressionCD30+CD30-0–10%8/40%15/65%11–30%5/25%5/22%31–50%4/20%2/8%>50%3/15%1/5%Total2023 Conclusions:Our preliminary data on 43 patients with SM/ CD30/123 expression suggests:1.There is no direct association between CD30/CD123 expression and more aggressive SM in our patient cohort based on immunocytochemistry of trephines and clinical classification.2.CD30/CD123 expression correlates with disease bulk when assessed by tryptase levels and trephine mast cell percentage: > 10% disease bulk seen in 60% CD30(+) vs 35% CD(−) SM patients.3.Further evaluation with increased numbers of patients needs to be carried out to confirm this. Disclosures:Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding.