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Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation

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Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation. / Gagelmann, Nico; Badbaran, Anita; Salit, Rachel B; Gurnari, Carmelo; Pagliuca, Simona; Panagiota, Victoria; Rautenberg, Christina; Cassinat, Bruno; Thol, Felicitas; Wolschke, Christine; Robin, Marie; Heuser, Michael; Rubio, Marie-Thérèse; Maciejewski, Jaroslaw P; Reinhardt, Hans Christian; Scott, Bart L; Kröger, Nicolaus.

In: BLOOD, Vol. 141, No. 23, 08.06.2023, p. 2901-2911.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gagelmann, N, Badbaran, A, Salit, RB, Gurnari, C, Pagliuca, S, Panagiota, V, Rautenberg, C, Cassinat, B, Thol, F, Wolschke, C, Robin, M, Heuser, M, Rubio, M-T, Maciejewski, JP, Reinhardt, HC, Scott, BL & Kröger, N 2023, 'Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation', BLOOD, vol. 141, no. 23, pp. 2901-2911. https://doi.org/10.1182/blood.2023019630

APA

Gagelmann, N., Badbaran, A., Salit, R. B., Gurnari, C., Pagliuca, S., Panagiota, V., Rautenberg, C., Cassinat, B., Thol, F., Wolschke, C., Robin, M., Heuser, M., Rubio, M-T., Maciejewski, J. P., Reinhardt, H. C., Scott, B. L., & Kröger, N. (2023). Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation. BLOOD, 141(23), 2901-2911. https://doi.org/10.1182/blood.2023019630

Vancouver

Gagelmann N, Badbaran A, Salit RB, Gurnari C, Pagliuca S, Panagiota V et al. Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation. BLOOD. 2023 Jun 8;141(23):2901-2911. https://doi.org/10.1182/blood.2023019630

Bibtex

@article{bf77a19c97544037bb3bf72f6ec7d453,
title = "Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation",
abstract = "TP53 mutations (TP53MTs) have been associated with poor outcomes in various hematologic malignancies, but no data exist regarding its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MT in this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multihit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of patients with TP53MT was 1.5 vs 13.5 years for those with wild-type TP53 (TP53WT; P < .001). Outcome was driven by multihit TP53MT constellation (P < .001), showing 6-year survival of 56% for individuals with single-hit vs 25% for those with multihit TP53MT vs 64% for those with TP53WT. Outcome was independent of current transplantation-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multihit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P < .001). Out of the 10 patients with TP53MT, 8 showed multihit constellation. Median time to leukemic transformation was shorter for multihit and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multihit TP53MT represents a very high-risk group in patients with myelofibrosis who are undergoing HSCT, whereas single-hit TP53MT alone showed similar outcome to patients with nonmutated TP53, informing prognostication for survival and relapse together with current transplantation-specific tools.",
keywords = "Humans, Primary Myelofibrosis/genetics, Graft vs Host Disease/etiology, Transplantation, Homologous/adverse effects, Neoplasm Recurrence, Local/etiology, Hematopoietic Stem Cell Transplantation/adverse effects, Transplantation Conditioning/adverse effects, Chronic Disease, Retrospective Studies, Tumor Suppressor Protein p53/genetics",
author = "Nico Gagelmann and Anita Badbaran and Salit, {Rachel B} and Carmelo Gurnari and Simona Pagliuca and Victoria Panagiota and Christina Rautenberg and Bruno Cassinat and Felicitas Thol and Christine Wolschke and Marie Robin and Michael Heuser and Marie-Th{\'e}r{\`e}se Rubio and Maciejewski, {Jaroslaw P} and Reinhardt, {Hans Christian} and Scott, {Bart L} and Nicolaus Kr{\"o}ger",
note = "{\textcopyright} 2023 by The American Society of Hematology.",
year = "2023",
month = jun,
day = "8",
doi = "10.1182/blood.2023019630",
language = "English",
volume = "141",
pages = "2901--2911",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "23",

}

RIS

TY - JOUR

T1 - Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation

AU - Gagelmann, Nico

AU - Badbaran, Anita

AU - Salit, Rachel B

AU - Gurnari, Carmelo

AU - Pagliuca, Simona

AU - Panagiota, Victoria

AU - Rautenberg, Christina

AU - Cassinat, Bruno

AU - Thol, Felicitas

AU - Wolschke, Christine

AU - Robin, Marie

AU - Heuser, Michael

AU - Rubio, Marie-Thérèse

AU - Maciejewski, Jaroslaw P

AU - Reinhardt, Hans Christian

AU - Scott, Bart L

AU - Kröger, Nicolaus

N1 - © 2023 by The American Society of Hematology.

PY - 2023/6/8

Y1 - 2023/6/8

N2 - TP53 mutations (TP53MTs) have been associated with poor outcomes in various hematologic malignancies, but no data exist regarding its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MT in this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multihit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of patients with TP53MT was 1.5 vs 13.5 years for those with wild-type TP53 (TP53WT; P < .001). Outcome was driven by multihit TP53MT constellation (P < .001), showing 6-year survival of 56% for individuals with single-hit vs 25% for those with multihit TP53MT vs 64% for those with TP53WT. Outcome was independent of current transplantation-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multihit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P < .001). Out of the 10 patients with TP53MT, 8 showed multihit constellation. Median time to leukemic transformation was shorter for multihit and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multihit TP53MT represents a very high-risk group in patients with myelofibrosis who are undergoing HSCT, whereas single-hit TP53MT alone showed similar outcome to patients with nonmutated TP53, informing prognostication for survival and relapse together with current transplantation-specific tools.

AB - TP53 mutations (TP53MTs) have been associated with poor outcomes in various hematologic malignancies, but no data exist regarding its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MT in this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multihit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of patients with TP53MT was 1.5 vs 13.5 years for those with wild-type TP53 (TP53WT; P < .001). Outcome was driven by multihit TP53MT constellation (P < .001), showing 6-year survival of 56% for individuals with single-hit vs 25% for those with multihit TP53MT vs 64% for those with TP53WT. Outcome was independent of current transplantation-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multihit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P < .001). Out of the 10 patients with TP53MT, 8 showed multihit constellation. Median time to leukemic transformation was shorter for multihit and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multihit TP53MT represents a very high-risk group in patients with myelofibrosis who are undergoing HSCT, whereas single-hit TP53MT alone showed similar outcome to patients with nonmutated TP53, informing prognostication for survival and relapse together with current transplantation-specific tools.

KW - Humans

KW - Primary Myelofibrosis/genetics

KW - Graft vs Host Disease/etiology

KW - Transplantation, Homologous/adverse effects

KW - Neoplasm Recurrence, Local/etiology

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Transplantation Conditioning/adverse effects

KW - Chronic Disease

KW - Retrospective Studies

KW - Tumor Suppressor Protein p53/genetics

U2 - 10.1182/blood.2023019630

DO - 10.1182/blood.2023019630

M3 - SCORING: Journal article

C2 - 36940410

VL - 141

SP - 2901

EP - 2911

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 23

ER -