Abstract

Abstract 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 1.

SM diagnosis and CD30 expression

DiagnosisTotalCD30 +CD30 -
Indolent SM ISM 26 10/30% 16/70% 
 SSM 2/100% 
Aggressive SM ASM 2/66% 1/33% 
 AHNMD 12 6/50% 6/50% 
DiagnosisTotalCD30 +CD30 -
Indolent SM ISM 26 10/30% 16/70% 
 SSM 2/100% 
Aggressive SM ASM 2/66% 1/33% 
 AHNMD 12 6/50% 6/50% 
Table 2:

CD123 expression and SM classification

CD123+CD123-
ISM 4/40% 19/63% 
SSM 2/20% 
ASM 1/10% 2/7% 
AHNMD 3/30% 9/30% 
Total 10 30 
CD123+CD123-
ISM 4/40% 19/63% 
SSM 2/20% 
ASM 1/10% 2/7% 
AHNMD 3/30% 9/30% 
Total 10 30 

Dual CD30/CD123 positive: 8/40 patients: 2 ISM / / 3 AHNMD.

Table 3:

Disease bulk on trephine and CD30 expression

CD30+CD30-
0–10% 8/40% 15/65% 
11–30% 5/25% 5/22% 
31–50% 4/20% 2/8% 
>50% 3/15% 1/5% 
Total 20 23 
CD30+CD30-
0–10% 8/40% 15/65% 
11–30% 5/25% 5/22% 
31–50% 4/20% 2/8% 
>50% 3/15% 1/5% 
Total 20 23 
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.

Author notes

*

Asterisk with author names denotes non-ASH members.