Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation

Nico Gagelmann, Diderik Jan Eikema, Matthias Stelljes, Dietrich Beelen, Liesbeth de Wreede, Ghulam Mufti, Nina Simone Knelange, Dietger Niederwieser, Lone S. Friis, Gerhard Ehninger, Arnon Nagler, Ibrahim Yakoub-Agha, Ellen Meijer, Per Ljungman, Johan Maertens, Lothar Kanz, Lucia Lopez-Corral, Arne Brecht, Charles Craddock, Jürgen FinkeJan J. Cornelissen, Paolo Bernasconi, Patrice Chevallier, Jorge Sierra, Marie Robin, Nicolaus Kröger

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The aim of this study was to develop and validate a clinical and transplant-specific prognostic score using data from a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was performed to evaluate the validity and consistency of the model. Seven independent risk factors for survival were identified: age ≥50 years, matched unrelated donor, Karnofsky Performance Status <90%, very poor cytogenetics or monosomal karyotype, positive cytomegalovirus status of the recipient, blood blasts >1%, and platelet count ≤50 × 109/L prior to transplantation. Incorporating these factors into a four-level risk score yielded hazard ratios for death, with low-risk (score of 0-1) as reference, of 2.02 (95% CI: 1.41-2.90) for the intermediate-risk group (score of 2-3), 3.49 (95% CI: 2.45-4.97) for the high-risk group (score of 4-5), and 5.90 (95% CI: 4.01-8.67) for the very high-risk group (score of >5). The score was predictive of survival, relapse-free survival, relapse, and non-relapse mortality (P<0.001, respectively). Cross-validation yielded significant and reproducible improvement in prognostic ability with C-statistics being 0.609 (95% CI: 0.588-0.629) versus 0.555 for the Gruppo Italiano Trapianto di Midollo Osseo registry and 0.579 for the Center for Blood and Marrow Transplant Research registry. Prediction was even further augmented after applying a nomogram using age and platelets as continuous variables showing C-statistics of 0.628 (95% CI: 0.616-0.637). In conclusion, compared to existing prognostic systems, this proposed transplant-specific risk score offers improved performance with respect to post-transplant risk stratification in myelodysplastic syndromes.

Original languageEnglish
Pages (from-to)929-936
Number of pages8
JournalHaematologica
Volume104
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Myelodysplastic Syndromes
Stem Cell Transplantation
Transplants
Registries
Survival
Transplantation
Bone Marrow
Karnofsky Performance Status
Recurrence
Unrelated Donors
Nomograms
Platelet Count
Proportional Hazards Models
Blood Platelets
Mortality
Research

ASJC Scopus subject areas

  • Hematology

Cite this

Gagelmann, N., Eikema, D. J., Stelljes, M., Beelen, D., de Wreede, L., Mufti, G., ... Kröger, N. (2019). Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation. Haematologica, 104(5), 929-936. https://doi.org/10.3324/haematol.2018.200808

Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation. / Gagelmann, Nico; Eikema, Diderik Jan; Stelljes, Matthias; Beelen, Dietrich; de Wreede, Liesbeth; Mufti, Ghulam; Knelange, Nina Simone; Niederwieser, Dietger; Friis, Lone S.; Ehninger, Gerhard; Nagler, Arnon; Yakoub-Agha, Ibrahim; Meijer, Ellen; Ljungman, Per; Maertens, Johan; Kanz, Lothar; Lopez-Corral, Lucia; Brecht, Arne; Craddock, Charles; Finke, Jürgen; Cornelissen, Jan J.; Bernasconi, Paolo; Chevallier, Patrice; Sierra, Jorge; Robin, Marie; Kröger, Nicolaus.

In: Haematologica, Vol. 104, No. 5, 01.05.2019, p. 929-936.

Research output: Contribution to journalArticle

Gagelmann, N, Eikema, DJ, Stelljes, M, Beelen, D, de Wreede, L, Mufti, G, Knelange, NS, Niederwieser, D, Friis, LS, Ehninger, G, Nagler, A, Yakoub-Agha, I, Meijer, E, Ljungman, P, Maertens, J, Kanz, L, Lopez-Corral, L, Brecht, A, Craddock, C, Finke, J, Cornelissen, JJ, Bernasconi, P, Chevallier, P, Sierra, J, Robin, M & Kröger, N 2019, 'Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation', Haematologica, vol. 104, no. 5, pp. 929-936. https://doi.org/10.3324/haematol.2018.200808
Gagelmann, Nico ; Eikema, Diderik Jan ; Stelljes, Matthias ; Beelen, Dietrich ; de Wreede, Liesbeth ; Mufti, Ghulam ; Knelange, Nina Simone ; Niederwieser, Dietger ; Friis, Lone S. ; Ehninger, Gerhard ; Nagler, Arnon ; Yakoub-Agha, Ibrahim ; Meijer, Ellen ; Ljungman, Per ; Maertens, Johan ; Kanz, Lothar ; Lopez-Corral, Lucia ; Brecht, Arne ; Craddock, Charles ; Finke, Jürgen ; Cornelissen, Jan J. ; Bernasconi, Paolo ; Chevallier, Patrice ; Sierra, Jorge ; Robin, Marie ; Kröger, Nicolaus. / Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation. In: Haematologica. 2019 ; Vol. 104, No. 5. pp. 929-936.
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T1 - Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation

AU - Gagelmann, Nico

AU - Eikema, Diderik Jan

AU - Stelljes, Matthias

AU - Beelen, Dietrich

AU - de Wreede, Liesbeth

AU - Mufti, Ghulam

AU - Knelange, Nina Simone

AU - Niederwieser, Dietger

AU - Friis, Lone S.

AU - Ehninger, Gerhard

AU - Nagler, Arnon

AU - Yakoub-Agha, Ibrahim

AU - Meijer, Ellen

AU - Ljungman, Per

AU - Maertens, Johan

AU - Kanz, Lothar

AU - Lopez-Corral, Lucia

AU - Brecht, Arne

AU - Craddock, Charles

AU - Finke, Jürgen

AU - Cornelissen, Jan J.

AU - Bernasconi, Paolo

AU - Chevallier, Patrice

AU - Sierra, Jorge

AU - Robin, Marie

AU - Kröger, Nicolaus

PY - 2019/5/1

Y1 - 2019/5/1

N2 - The aim of this study was to develop and validate a clinical and transplant-specific prognostic score using data from a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was performed to evaluate the validity and consistency of the model. Seven independent risk factors for survival were identified: age ≥50 years, matched unrelated donor, Karnofsky Performance Status <90%, very poor cytogenetics or monosomal karyotype, positive cytomegalovirus status of the recipient, blood blasts >1%, and platelet count ≤50 × 109/L prior to transplantation. Incorporating these factors into a four-level risk score yielded hazard ratios for death, with low-risk (score of 0-1) as reference, of 2.02 (95% CI: 1.41-2.90) for the intermediate-risk group (score of 2-3), 3.49 (95% CI: 2.45-4.97) for the high-risk group (score of 4-5), and 5.90 (95% CI: 4.01-8.67) for the very high-risk group (score of >5). The score was predictive of survival, relapse-free survival, relapse, and non-relapse mortality (P<0.001, respectively). Cross-validation yielded significant and reproducible improvement in prognostic ability with C-statistics being 0.609 (95% CI: 0.588-0.629) versus 0.555 for the Gruppo Italiano Trapianto di Midollo Osseo registry and 0.579 for the Center for Blood and Marrow Transplant Research registry. Prediction was even further augmented after applying a nomogram using age and platelets as continuous variables showing C-statistics of 0.628 (95% CI: 0.616-0.637). In conclusion, compared to existing prognostic systems, this proposed transplant-specific risk score offers improved performance with respect to post-transplant risk stratification in myelodysplastic syndromes.

AB - The aim of this study was to develop and validate a clinical and transplant-specific prognostic score using data from a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was performed to evaluate the validity and consistency of the model. Seven independent risk factors for survival were identified: age ≥50 years, matched unrelated donor, Karnofsky Performance Status <90%, very poor cytogenetics or monosomal karyotype, positive cytomegalovirus status of the recipient, blood blasts >1%, and platelet count ≤50 × 109/L prior to transplantation. Incorporating these factors into a four-level risk score yielded hazard ratios for death, with low-risk (score of 0-1) as reference, of 2.02 (95% CI: 1.41-2.90) for the intermediate-risk group (score of 2-3), 3.49 (95% CI: 2.45-4.97) for the high-risk group (score of 4-5), and 5.90 (95% CI: 4.01-8.67) for the very high-risk group (score of >5). The score was predictive of survival, relapse-free survival, relapse, and non-relapse mortality (P<0.001, respectively). Cross-validation yielded significant and reproducible improvement in prognostic ability with C-statistics being 0.609 (95% CI: 0.588-0.629) versus 0.555 for the Gruppo Italiano Trapianto di Midollo Osseo registry and 0.579 for the Center for Blood and Marrow Transplant Research registry. Prediction was even further augmented after applying a nomogram using age and platelets as continuous variables showing C-statistics of 0.628 (95% CI: 0.616-0.637). In conclusion, compared to existing prognostic systems, this proposed transplant-specific risk score offers improved performance with respect to post-transplant risk stratification in myelodysplastic syndromes.

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