Revised cytogenetic risk stratification in primary myelofibrosis

analysis based on 1002 informative patients

Ayalew Tefferi, Maura Nicolosi, Mythri Mudireddy, Terra L. Lasho, Naseema Gangat, Kebede Begna, Curtis A. Hanson, Rhett P. Ketterling, Animesh D Pardanani

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalLeukemia
DOIs
StateAccepted/In press - Feb 2 2018

Fingerprint

Primary Myelofibrosis
Cytogenetics
Survival
Mutation
Sex Chromosome Aberrations
Multiple Abnormalities
Chromosomes, Human, Pair 1
Trisomy
Karyotype
Chromosome Aberrations

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Revised cytogenetic risk stratification in primary myelofibrosis : analysis based on 1002 informative patients. / Tefferi, Ayalew; Nicolosi, Maura; Mudireddy, Mythri; Lasho, Terra L.; Gangat, Naseema; Begna, Kebede; Hanson, Curtis A.; Ketterling, Rhett P.; Pardanani, Animesh D.

In: Leukemia, 02.02.2018, p. 1-11.

Research output: Contribution to journalArticle

Tefferi, Ayalew ; Nicolosi, Maura ; Mudireddy, Mythri ; Lasho, Terra L. ; Gangat, Naseema ; Begna, Kebede ; Hanson, Curtis A. ; Ketterling, Rhett P. ; Pardanani, Animesh D. / Revised cytogenetic risk stratification in primary myelofibrosis : analysis based on 1002 informative patients. In: Leukemia. 2018 ; pp. 1-11.
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abstract = "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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AU - Gangat, Naseema

AU - Begna, Kebede

AU - Hanson, Curtis A.

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