TY - JOUR
T1 - Cytogenetic abnormalities in systemic mastocytosis
T2 - WHO subcategory-specific incidence and prognostic impact among 348 informative cases
AU - Shah, Sahrish
AU - Pardanani, Animesh
AU - Elala, Yoseph C.
AU - Lasho, Terra L.
AU - Patnaik, Mrinal M.
AU - Reichard, Kaaren K.
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Tefferi, Ayalew
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/12
Y1 - 2018/12
N2 - The World Health Organization (WHO) system lists five morphological categories of systemic mastocytosis (SM): indolent (ISM), smoldering, SM with an associated hematological neoplasm (SM-AHN), aggressive (ASM) and mast cell leukemia (MCL). Recent studies have highlighted the prognostic importance of mutations in SM, including ASXL1, RUNX1, and SRSF2. In contrast, information on incidence of cytogenetic abnormalities in SM and their prognostic relevance, especially in the context of mutations, is limited. In the current study, we retrospectively reviewed the cytogenetic findings in 348 consecutive cases of SM (median age 59 years; 53% males); 41% constituted ISM, 45% SM-AHN, 14% ASM and two cases of MCL. Karyotype was abnormal in 53 (15%) cases with incidences of 6% for ISM, 26% for SM-AHN and 8% for ASM (P <.001); among SM-AHN cases, abnormal karyotype incidences were 0% for SM-AHN-lymphoid and 28% for SM-AHN-myeloid (P <.001). Clinical correlative studies disclosed significant associations between abnormal karyotype and male sex (P =.002), age > 60 years (P =.04), thrombocytopenia (P <.001) and anemia (P <.001), but not with the presence of adverse mutations (P =.19). In univariate analysis, abnormal karyotype was associated with inferior survival (HR 3.0, 95% CI 2.0-4.3), specifically confirmed for ASM (HR 4.9, 95% CI 1.1-16.1) and SM-AHN (HR 1.8, 95% CI 1.2-2.7). Sample size adequacy allowed additional multivariable analysis in SM-AHN-myeloid, which disclosed independent prognostic contribution from adverse mutations (P =.003), anemia (P =.003) and thrombocytopenia (P =.001), but not from abnormal karyotype (P =.31). Our observations suggest that mutations are prognostically more relevant than karyotype in SM.
AB - The World Health Organization (WHO) system lists five morphological categories of systemic mastocytosis (SM): indolent (ISM), smoldering, SM with an associated hematological neoplasm (SM-AHN), aggressive (ASM) and mast cell leukemia (MCL). Recent studies have highlighted the prognostic importance of mutations in SM, including ASXL1, RUNX1, and SRSF2. In contrast, information on incidence of cytogenetic abnormalities in SM and their prognostic relevance, especially in the context of mutations, is limited. In the current study, we retrospectively reviewed the cytogenetic findings in 348 consecutive cases of SM (median age 59 years; 53% males); 41% constituted ISM, 45% SM-AHN, 14% ASM and two cases of MCL. Karyotype was abnormal in 53 (15%) cases with incidences of 6% for ISM, 26% for SM-AHN and 8% for ASM (P <.001); among SM-AHN cases, abnormal karyotype incidences were 0% for SM-AHN-lymphoid and 28% for SM-AHN-myeloid (P <.001). Clinical correlative studies disclosed significant associations between abnormal karyotype and male sex (P =.002), age > 60 years (P =.04), thrombocytopenia (P <.001) and anemia (P <.001), but not with the presence of adverse mutations (P =.19). In univariate analysis, abnormal karyotype was associated with inferior survival (HR 3.0, 95% CI 2.0-4.3), specifically confirmed for ASM (HR 4.9, 95% CI 1.1-16.1) and SM-AHN (HR 1.8, 95% CI 1.2-2.7). Sample size adequacy allowed additional multivariable analysis in SM-AHN-myeloid, which disclosed independent prognostic contribution from adverse mutations (P =.003), anemia (P =.003) and thrombocytopenia (P =.001), but not from abnormal karyotype (P =.31). Our observations suggest that mutations are prognostically more relevant than karyotype in SM.
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U2 - 10.1002/ajh.25265
DO - 10.1002/ajh.25265
M3 - Article
C2 - 30152525
AN - SCOPUS:85053925151
SN - 0361-8609
VL - 93
SP - 1461
EP - 1466
JO - American journal of hematology
JF - American journal of hematology
IS - 12
ER -