Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R

Ayalew Tefferi, Terra L. Lasho, Mrinal M Patnaik, Lyla Saeed, Mythri Mudireddy, Dame Idossa, Christy Finke, Rhett P. Ketterling, Animesh D Pardanani, Naseema Gangat

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Abstract

A 27-gene panel was used for next-generation sequencing (NGS) in 179 patients (median age 73 years) with primary myelodysplastic syndromes (MDS); risk distribution according to the revised International Prognostic Scoring System (IPSS-R) was 11% very high, 18% high, 17% intermediate, 38% low and 16% very low. At least one mutation/variant was detected in 147 (82%) patients; 23% harbored three or more mutations/variants. The most frequent mutations/variants included ASXL1 (30%), TET2 (25%), SF3B1 (20%), U2AF1 (16%), SRSF2 (16%), TP53 (13%), RUNX1 (11%), and DNMT3A (10%). At a median follow up of 30 months, 148 (83%) deaths and 26 (15%) leukemic transformations were recorded. Multivariable analysis of mutations/variants identified ASXL1 (HR 1.7, 95% CI 1.2-2.5), SETBP1 (HR 4.1, 95% CI 1.6-10.2) and TP53 (HR 2.2, 95% CI 1.3-3.4) as risk factors for overall and SRSF2 (HR 3.9, 95% CI 1.5-10.2), IDH2 (HR 3.7, 95% CI 1.2-11.4), and CSF3R (HR 6.0, 95% CI 1.6-22.6) for leukemia-free survival. Addition of age to the multivariable model did not affect these results while accounting for IPSS-R weakened the significance of TP53 mutations/variants (P =.1). An apparently favorable survival impact of SF3B1 mutations was no longer evident after adjustment for IPSS-R. Approximately 41% and 20% of patients harbored at least one adverse mutation/variant for overall and leukemia-free survival, respectively. Number of mutations/variants did not provide additional prognostic value. The survival impact of adverse mutations was most evident in IPSS-R very low/low risk patients. These observations suggest that targeted NGS might assist in treatment decision-making in lower risk MDS.

Original languageEnglish (US)
Pages (from-to)1311-1317
Number of pages7
JournalAmerican Journal of Hematology
Volume92
Issue number12
DOIs
StatePublished - Dec 1 2017

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Myelodysplastic Syndromes
Mutation
Survival
Leukemia
Decision Making

ASJC Scopus subject areas

  • Hematology

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Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R. / Tefferi, Ayalew; Lasho, Terra L.; Patnaik, Mrinal M; Saeed, Lyla; Mudireddy, Mythri; Idossa, Dame; Finke, Christy; Ketterling, Rhett P.; Pardanani, Animesh D; Gangat, Naseema.

In: American Journal of Hematology, Vol. 92, No. 12, 01.12.2017, p. 1311-1317.

Research output: Contribution to journalArticle

Tefferi, Ayalew ; Lasho, Terra L. ; Patnaik, Mrinal M ; Saeed, Lyla ; Mudireddy, Mythri ; Idossa, Dame ; Finke, Christy ; Ketterling, Rhett P. ; Pardanani, Animesh D ; Gangat, Naseema. / Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R. In: American Journal of Hematology. 2017 ; Vol. 92, No. 12. pp. 1311-1317.
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AU - Mudireddy, Mythri

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