TY - JOUR
T1 - Revised cytogenetic risk stratification in primary myelofibrosis
T2 - Analysis based on 1002 informative patients
AU - Tefferi, Ayalew
AU - Nicolosi, Maura
AU - Mudireddy, Mythri
AU - Lasho, Terra L.
AU - Gangat, Naseema
AU - Begna, Kebede H.
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Pardanani, Animesh
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: 'favorable' and 'unfavorable'. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: 'very high risk (VHR)' - single/multiple abnormalities of -7, i(17q), inv(3)/3q21, 12p-/12p11.2, 11q-/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); 'favorable' - normal karyotype or sole abnormalities of 13q-, +9, 20q-, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; 'unfavorable' - all other abnormalities. Median survivals for VHR (n = 75), unfavorable (n = 190) and favorable (n = 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9-4.9), 2.9 (HR 1.7, 95% CI 1.4-2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and ASXL1/SRSF2 mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0-9.4) for VHR and 2.0 (1.2-3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of ASXL1/SRSF2 mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model.
AB - Current cytogenetic risk stratification in primary myelofibrosis (PMF) is two-tiered: 'favorable' and 'unfavorable'. Recent studies have suggested prognostic heterogeneity within the unfavorable risk category. In 1002 consecutive patients, we performed stepwise analysis of impact on survival from individual and prognostically ordered cytogenetic abnormalities, leading to a revised three-tiered risk model: 'very high risk (VHR)' - single/multiple abnormalities of -7, i(17q), inv(3)/3q21, 12p-/12p11.2, 11q-/11q23, or other autosomal trisomies not including + 8/ + 9 (e.g., +21, +19); 'favorable' - normal karyotype or sole abnormalities of 13q-, +9, 20q-, chromosome 1 translocation/duplication or sex chromosome abnormality including -Y; 'unfavorable' - all other abnormalities. Median survivals for VHR (n = 75), unfavorable (n = 190) and favorable (n = 737) risk categories were 1.2 (HR 3.8, 95% CI 2.9-4.9), 2.9 (HR 1.7, 95% CI 1.4-2.0) and 4.4 years and survival impact was independent of clinically derived prognostic systems, driver and ASXL1/SRSF2 mutations. The revised model was also effective in predicting leukemic transformation: HRs (95% CI) were 4.4 (2.0-9.4) for VHR and 2.0 (1.2-3.4) for unfavorable. The impact of driver mutations on survival was confined to favorable and that of ASXL1/SRSF2 mutations to favorable/unfavorable cytogenetic risk categories. The current study clarifies the prognostic hierarchy of genetic risk factors in PMF and provides a more refined three-tiered cytogenetic risk model.
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U2 - 10.1038/s41375-018-0018-z
DO - 10.1038/s41375-018-0018-z
M3 - Article
C2 - 29472717
AN - SCOPUS:85042359567
SN - 0887-6924
VL - 32
SP - 1189
EP - 1199
JO - Leukemia
JF - Leukemia
IS - 5
ER -