[en] Purpose: Survival of acute leukemia (AL) patients following umbilical cord blood transplantation (UCBT) is dependent on an array of individual features. Integrative models for risk assessment are lacking. We sought to develop a scoring system for prediction of overall survival (OS) and leukemia-free survival (LFS) at 2 years following UCBT in AL patients.Experimental Design: The study cohort included 3,140 pediatric and adult AL UCBT patients from the European Society of Blood and Marrow Transplantation and Eurocord registries. Patients received single or double cord blood units. The dataset was geographically split into a derivation (n = 2,362, 65%) and validation set (n = 778, 35%). Top predictors of OS were identified using the Random Survival Forest algorithm and introduced into a Cox regression model, which served for the construction of the UCBT risk score.Results: The score includes nine variables: disease status, diagnosis, cell dose, age, center experience, cytomegalovirus serostatus, degree of HLA mismatch, previous autograft, and anti-thymocyte globulin administration. Over the validation set an increasing score was associated with decreasing probabilities for 2 years OS and LFS, ranging from 70.21% [68.89-70.71, 95% confidence interval (CI)] and 64.76% (64.33-65.86, 95% CI) to 14.78% (10.91-17.41) and 18.11% (14.40-22.30), respectively. It stratified patients into six distinct risk groups. The score's discrimination (AUC) over multiple imputations of the validation set was 68.76 (68.19-69.04, range) and 65.78 (65.20-66.28) for 2 years OS and LFS, respectively.Conclusions: The UCBT score is a simple tool for risk stratification of AL patients undergoing UCBT. Widespread application of the score will require further independent validation. Clin Cancer Res; 23(21); 6478-86. (c)2017 AACR.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med 2016;375:944–53.
Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood 2013;122:491–8.
Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007;369:1947–54.
Herr AL, Kabbara N, Bonfim CM, Teira P, Locatelli F, Tiedemann K, et al. Long-term follow-up and factors influencing outcomes after related HLA-identical cord blood transplantation for patients with malignancies: an analysis on behalf of Eurocord-EBMT. Blood 2010;116:1849–56.
Cohen YC, Scaradavou A, Stevens CE, Rubinstein P, Gluckman E, Rocha V, et al. Factors affecting mortality following myeloablative cord blood transplantation in adults: a pooled analysis of three international registries. Bone Marrow Transplant 2011;46:70–6.
Barker JN, Scaradavou A, Stevens CE. Combined effect of total nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematologic malignancies. Blood 2010;115:1843–9.
Eapen M, Klein JP, Ruggeri A, Spellman S, Lee SJ, Anasetti C, et al. Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. Blood 2014;123:133–40.
Pascal L, Tucunduva L, Ruggeri A, Blaise D, Ceballos P, Chevallier P, et al. Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation. Blood 2015;126: 1027–32.
Hough R, Danby R, Russell N, Marks D, Veys P, Shaw B, et al. Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols. Br J Haematol 2016;172:360–70.
Scaradavou A, Brunstein CG, Eapen M, Le-Rademacher J, Barker JN, Chao N, et al. Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia. Blood 2013;121: 752–8.
Ruggeri A, Sanz G, Bittencourt H, Sanz J, Rambaldi A, Volt F, et al. Comparison of outcomes after single or double cord blood transplantation in adults with acute leukemia using different types of myeloablative conditioning regimen, a retrospective study on behalf of Eurocord and the Acute Leukemia Working Party of EBMT. Leukemia 2014;28:779–86.
Moons KG, Altman DG, Reitsma JB, Ioannidis JP, Macaskill P, Steyerberg EW, et al. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med 2015;162:W1–W73.
Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453–74.
Su YS, Yajima M, Gelman AE, Hill J. Multiple imputation with diagnostics (mi) in R: opening windows into the black box. J Stat Software 2011;45: 1–31.
Moons KG, Donders RA, Stijnen T, Harrell FE Jr. Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol 2006;59:1092–101.
Ishwaran H, Kogalur UB, Blackstone EH, Lauer MS. Random survival forests. Ann Appl Stat 2008;2:841–60.
Hsich E, Gorodeski EZ, Blackstone EH, Ishwaran H, Lauer MS. Identifying important risk factors for survival in patient with systolic heart failure using random survival forests. Circulation 2011;4:39–45.
Ishwaran H, Kogalur UB, Gorodeski EZ, Minn AJ, Lauer MS. High-dimensional variable selection for survival data. J Am Stat Assoc 2010;105: 205–17.
Inuzuka R, Diller G-P, Borgia F, Benson L, Tay EL, Alonso-Gonzalez R, et al. Comprehensive use of cardiopulmonary exercise testing identifies adults with congenital heart disease at increased mortality risk in the medium term. Circulation 2012;125:250–9.
Marshall A, Altman DG, Holder RL, Royston P. Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med Res Methodol 2009;9:57.
Blanche P, Dartigues JF, Jacqmin-Gadda H. Estimating and comparing timedependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med 2013;32:5381–97.
Shouval R, Labopin M, Bondi O, Mishan-Shamay H, Shimoni A, Ciceri F, et al. Prediction of allogeneic hematopoietic stem-cell transplantation mortality 100 days after transplantation using a machine learning algorithm: a European group for blood and marrow transplantation acute leukemia working party retrospective data mining study. J Clin Oncol 2015;33:3144–51.
Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, et al. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia 2015;29:1891–900.
Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T, et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation a retrospective analysis. Cancer 2009;115:4715–26.
Parimon T, Au DH, Martin PJ, Chien JW. A risk score for mortality after allogeneic hematopoietic cell transplantation. Ann Intern Med 2006;144: 407–14.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106:2912–9.
Eapen M, Klein JP, Sanz GF, Spellman S, Ruggeri A, Anasetti C, et al. Effect of donor–recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol 2011;12: 1214–21.
Admiraal R, van Kesteren C, Jol-van der Zijde CM, Lankester AC, Bierings MB, Egberts TC, et al. Association between anti-thymocyte globulin exposure and CD4þ immune reconstitution in paediatric haemopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis. Lancet Haematol 2015;2:e194–e203.
Lindemans CA, Chiesa R, Amrolia PJ, Rao K, Nikolajeva O, de Wildt A, et al. Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood 2014;123:126–32.
Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, et al. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 2014;371:1685–94.
Baron F, Ruggeri A, Beohou E, Labopin M, Sanz G, Milpied N, et al. RIC versus MAC UCBT in adults with AML: a report from Eurocord, the ALWP and the CTIWP of the EBMT. Oncotarget 2016;7:43027–38.
Michel G, Galambrun C, Sirvent A, Pochon C, Bruno B, Jubert C, et al. Single versus double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome. Blood 2016;127:3450–7.
Frassoni F, Labopin M, Powles R, Mary JY, Arcese W, Bacigalupo A, et al. Effect of centre on outcome of bone-marrow transplantation for acute myeloid leukaemia. Acute leukaemia working party of the European group for blood and marrow transplantation. Lancet 2000;355: 1393–8.
Gratwohl A, Brand R, Niederwieser D, Baldomero H, Chabannon C, Cornelissen J, et al. Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation. J Clin Oncol 2011;29:1980–6.
Giebel S, Labopin M, Mohty M, Mufti GJ, Niederwieser D, Cornelissen JJ, et al. The impact of center experience on results of reduced intensity: allogeneic hematopoietic SCT for AML. An analysis from the acute leukemia working party of the EBMT. Bone Marrow Transplant 2012;48: 238–42.
Shouval R, Bonifazi F, Fein J, Boschini C, Oldani E, Labopin M, et al. Validation of the acute leukemiaEBMT score for prediction of mortality following allogeneic stem cell transplantation in a multicenter GITMO cohort. Am J Hematol 2017;92:429–34.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.