Contributions
Abstract: PB2258
Type: Publication Only
Background
Systemic Mastocytosis (SM) is a complex disorder characterized by the accumulation of abnormal mast cells (MCs) in different organs and a wide spectrum of symptoms, derived from abnormal MCs degranulation. The diagnosis is based on serum baseline tryptase (sBT) level, histopathological, morphologic and immunophenotypic evaluation of MCs and D816V mutation. Diagnosis and cure of SM is peculiar, and patients have to be referred to specialized centers. In some cases, with a very small percentage of MCs in bone marrow (BM), diagnosis is difficult, because major diagnostic criteria (MDC) are often missing, sBT may be < 20 ug/L, and very sensitive methods for detection of D816V mutation are required to avoid false negative results. Once a diagnosis of SM is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Evaluation of sBT levels have been associated with the burden of disease, especially in ISM, whereas in ASM and MCL sBT level varies. Tryptase can be easily measured in many laboratories, in contrast to FC and high sensitive molecular methods.
Aims
to explore the utility of bone marrow tryptase (bmT) level for predicting disease diagnosis and behavior.
Methods
We systematically explored the bmT level in 39 patients with suspected SM, with sBT level, histopathological, morphologic and immunophenotypic evaluation of MCs and molecular analysis. The commercial technique Immuno CAP Tryptase System was used. To exclude lower level of bmT due to hemodilution of the sample, we performed the tryptase assay on the same sample used for the FC analysis considering eventual increased T-lymphocyte count. Moreover we evaluated bmT level in 16 BM samples analysed with FC for other hematological/suspected hematological diseases. bmT levels were correlated with all the others diagnostic parameters, including an accurate morphologic examination, and with the final diagnosis and classification according to WHO.
Results
the median bmT level was 230 ug/L in patients with SM diagnosis (IQR 123-471), whereas 14.95 in normal BM (IQR 6.52-26,30) ; p 0.0001. The bmT level is different in the categories of disease (ISM, SSM, ASM and LMC), with low significance (p= 0.0244), due to the predominance of ISM, but importantly this difference is lost considering together ASM and MCL forms versus the ISM. bmT level is elevated in patients without MDC (histopathological, presence of aggregates with more than 15 elements) as in the patients with the MDC, with 190.5 ug/L (IQR 95-345) in the first group and 230 (IQR 169-473) in the former, instead of 17.75 (IQR 14.6-19.10) versus 34 (IQR 20.6-105) for sBT level (p = 0.0073). There is a correlation between bmT Level and percentage of MCs in BM, although less strong than in the case of sBT level. Correlations between bmT Level and morphological aspects of the BM smears show an higher median value in cases with mature forms of MCs ( 387 ug/L versus 135.5 ug/L, with p = 0.0878), but without significance. No correlations were found with CD2 or CD25 expression.
Conclusion
high bmT level is closely associated with diagnosis of SM. Evaluation of bmT level can be integrated in the diagnostic process of SM due to its feasibility, in particular in ISM, where it can identify ISM with very low percentage of MCs. The variability of bmT Level in advanced forms highlights the need of different parameters for the disease characterization of MCL, ASM, and probably a subset of SSM, as the maturation markers of MCs in FC, or new Molecular alterations.
Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research
Keyword(s): Bone marrow involvement, flow cytometry, Mast cell disease, WHO classification
Abstract: PB2258
Type: Publication Only
Background
Systemic Mastocytosis (SM) is a complex disorder characterized by the accumulation of abnormal mast cells (MCs) in different organs and a wide spectrum of symptoms, derived from abnormal MCs degranulation. The diagnosis is based on serum baseline tryptase (sBT) level, histopathological, morphologic and immunophenotypic evaluation of MCs and D816V mutation. Diagnosis and cure of SM is peculiar, and patients have to be referred to specialized centers. In some cases, with a very small percentage of MCs in bone marrow (BM), diagnosis is difficult, because major diagnostic criteria (MDC) are often missing, sBT may be < 20 ug/L, and very sensitive methods for detection of D816V mutation are required to avoid false negative results. Once a diagnosis of SM is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Evaluation of sBT levels have been associated with the burden of disease, especially in ISM, whereas in ASM and MCL sBT level varies. Tryptase can be easily measured in many laboratories, in contrast to FC and high sensitive molecular methods.
Aims
to explore the utility of bone marrow tryptase (bmT) level for predicting disease diagnosis and behavior.
Methods
We systematically explored the bmT level in 39 patients with suspected SM, with sBT level, histopathological, morphologic and immunophenotypic evaluation of MCs and molecular analysis. The commercial technique Immuno CAP Tryptase System was used. To exclude lower level of bmT due to hemodilution of the sample, we performed the tryptase assay on the same sample used for the FC analysis considering eventual increased T-lymphocyte count. Moreover we evaluated bmT level in 16 BM samples analysed with FC for other hematological/suspected hematological diseases. bmT levels were correlated with all the others diagnostic parameters, including an accurate morphologic examination, and with the final diagnosis and classification according to WHO.
Results
the median bmT level was 230 ug/L in patients with SM diagnosis (IQR 123-471), whereas 14.95 in normal BM (IQR 6.52-26,30) ; p 0.0001. The bmT level is different in the categories of disease (ISM, SSM, ASM and LMC), with low significance (p= 0.0244), due to the predominance of ISM, but importantly this difference is lost considering together ASM and MCL forms versus the ISM. bmT level is elevated in patients without MDC (histopathological, presence of aggregates with more than 15 elements) as in the patients with the MDC, with 190.5 ug/L (IQR 95-345) in the first group and 230 (IQR 169-473) in the former, instead of 17.75 (IQR 14.6-19.10) versus 34 (IQR 20.6-105) for sBT level (p = 0.0073). There is a correlation between bmT Level and percentage of MCs in BM, although less strong than in the case of sBT level. Correlations between bmT Level and morphological aspects of the BM smears show an higher median value in cases with mature forms of MCs ( 387 ug/L versus 135.5 ug/L, with p = 0.0878), but without significance. No correlations were found with CD2 or CD25 expression.
Conclusion
high bmT level is closely associated with diagnosis of SM. Evaluation of bmT level can be integrated in the diagnostic process of SM due to its feasibility, in particular in ISM, where it can identify ISM with very low percentage of MCs. The variability of bmT Level in advanced forms highlights the need of different parameters for the disease characterization of MCL, ASM, and probably a subset of SSM, as the maturation markers of MCs in FC, or new Molecular alterations.
Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research
Keyword(s): Bone marrow involvement, flow cytometry, Mast cell disease, WHO classification