TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q)

Ayalew Tefferi; Farah Fleti; Onyee Chan; Najla H. Al Ali; Aref Al-Kali; Kebede H. Begna; James M. Foran; Talha Badar; Nandita Khera; Mithun Shah; Devendra Hiwase; Eric Padron; David A. Sallman; Animesh Pardanani; Daniel A. Arber; Attilio Orazi; Kaaren K. Reichard; Rong He; Rhett P. Ketterling; Naseema Gangat; Rami Komrokji

doi:10.1111/bjh.19247

TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q)

Ayalew Tefferi, Farah Fleti, Onyee Chan, Najla H. Al Ali, Aref Al-Kali, Kebede H. Begna, James M. Foran, Talha Badar, Nandita Khera, Mithun Shah, Devendra Hiwase, Eric Padron, David A. Sallman, Animesh Pardanani, Daniel A. Arber, Attilio Orazi, Kaaren K. Reichard, Rong He, Rhett P. Ketterling, Naseema GangatRami Komrokji

Research output: Contribution to journal › Article › peer-review

Abstract

Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.3) and TP53 variant allele frequency (VAF) ≥22% (p < 0.01; HR 2.8), but not SF3B1 mutation (p = 0.65), as independent risk factors for survival. Median survival was 11.7 versus 4 years (5/10-year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia-free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision-making in MDS-del(5q) regarding allogeneic stem cell transplant.

Original language	English (US)
Pages (from-to)	1243-1248
Number of pages	6
Journal	British journal of haematology
Volume	204
Issue number	4
DOIs	https://doi.org/10.1111/bjh.19247
State	Published - Apr 2024

Keywords

SF3B1
cytogenetics
mutation
prognosis
survival

ASJC Scopus subject areas

Hematology

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10.1111/bjh.19247

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Tefferi, A., Fleti, F., Chan, O., Al Ali, N. H., Al-Kali, A., Begna, K. H., Foran, J. M., Badar, T., Khera, N., Shah, M., Hiwase, D., Padron, E., Sallman, D. A., Pardanani, A., Arber, D. A., Orazi, A., Reichard, K. K., He, R., Ketterling, R. P., ... Komrokji, R. (2024). TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q). British journal of haematology, 204(4), 1243-1248. https://doi.org/10.1111/bjh.19247

Tefferi, A, Fleti, F, Chan, O, Al Ali, NH, Al-Kali, A, Begna, KH , Foran, JM, Badar, T, Khera, N, Shah, M, Hiwase, D, Padron, E, Sallman, DA, Pardanani, A, Arber, DA, Orazi, A, Reichard, KK, He, R, Ketterling, RP, Gangat, N & Komrokji, R 2024, 'TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q)', British journal of haematology, vol. 204, no. 4, pp. 1243-1248. https://doi.org/10.1111/bjh.19247

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title = "TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q)",

abstract = "Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.3) and TP53 variant allele frequency (VAF) ≥22% (p < 0.01; HR 2.8), but not SF3B1 mutation (p = 0.65), as independent risk factors for survival. Median survival was 11.7 versus 4 years (5/10-year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia-free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision-making in MDS-del(5q) regarding allogeneic stem cell transplant.",

keywords = "SF3B1, cytogenetics, mutation, prognosis, survival",

author = "Ayalew Tefferi and Farah Fleti and Onyee Chan and Al Ali, {Najla H.} and Aref Al-Kali and Begna, {Kebede H.} and Foran, {James M.} and Talha Badar and Nandita Khera and Mithun Shah and Devendra Hiwase and Eric Padron and Sallman, {David A.} and Animesh Pardanani and Arber, {Daniel A.} and Attilio Orazi and Reichard, {Kaaren K.} and Rong He and Ketterling, {Rhett P.} and Naseema Gangat and Rami Komrokji",

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year = "2024",

month = apr,

doi = "10.1111/bjh.19247",

language = "English (US)",

volume = "204",

pages = "1243--1248",

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T1 - TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q)

AU - Tefferi, Ayalew

AU - Fleti, Farah

AU - Chan, Onyee

AU - Al Ali, Najla H.

AU - Al-Kali, Aref

AU - Begna, Kebede H.

AU - Foran, James M.

AU - Badar, Talha

AU - Khera, Nandita

AU - Shah, Mithun

AU - Hiwase, Devendra

AU - Padron, Eric

AU - Sallman, David A.

AU - Pardanani, Animesh

AU - Arber, Daniel A.

AU - Orazi, Attilio

AU - Reichard, Kaaren K.

AU - He, Rong

AU - Ketterling, Rhett P.

AU - Gangat, Naseema

AU - Komrokji, Rami

PY - 2024/4

Y1 - 2024/4

N2 - Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.3) and TP53 variant allele frequency (VAF) ≥22% (p < 0.01; HR 2.8), but not SF3B1 mutation (p = 0.65), as independent risk factors for survival. Median survival was 11.7 versus 4 years (5/10-year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia-free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision-making in MDS-del(5q) regarding allogeneic stem cell transplant.

AB - Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.3) and TP53 variant allele frequency (VAF) ≥22% (p < 0.01; HR 2.8), but not SF3B1 mutation (p = 0.65), as independent risk factors for survival. Median survival was 11.7 versus 4 years (5/10-year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia-free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision-making in MDS-del(5q) regarding allogeneic stem cell transplant.

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KW - cytogenetics

KW - mutation

KW - prognosis

KW - survival

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JF - British journal of haematology

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ER -

TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q)

Abstract

Keywords

ASJC Scopus subject areas

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