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Stem Cell Transplantation
Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time-dependent effects
Daniel Fuerst,1,2* Sandra Frank,3,4* Carlheinz Mueller,4,5 Dietrich W Beelen,4,6 Johannes Schetelig,7 Dietger Niederwieser,8 Jürgen Finke,9 Donald Bunjes,10 Nicolaus Kröger,11 Christine Neuchel,1,2 Chrysanthi Tsamadou,1,2 Hubert Schrezenmeier,1,2 Jan Beyersmann3 and Joannis Mytilineos1,2,4
Ferrata Storti Foundation
1Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service, Baden Wuerttemberg – Hessen and University Clinic Ulm; 2Institute of Transfusion Medicine, University of Ulm; 3Institute of Statistics, University of Ulm; 4DRST – German Registry for Stem Cell Transplantation; 5Zentrales Knochenmarkspender-Register Deutschland (ZKRD - German Bone Marrow Donor Registry), Ulm; 6Department of Bone Marrow Transplantation, University Hospital, University of Duisburg-Essen, Essen; 7Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden; 8Department of Hematology/Oncology, University of Leipzig; 9Faculty of Medicine and Medical Center, University of Freiburg; 10Department of Internal Medicine III, University of Ulm and 11Department for Stem Cell Transplantation, University Cancer Center Hamburg, Germany
Haematologica 2018 Volume 103(9):1527-1534
DF and SF contributed equally to this work.
ABSTRACT
The success of hematopoietic stem cell transplantation is deter- mined by multiple factors. Additional complexity is conferred by covariables showing time-dependent effects. We evaluated the effect of predictors on competing-risk outcomes after hematopoietic stem cell transplantation in a time-dependent manner. We analyzed 14951 outcomes of adult patients with hematologic malignancies who underwent a first allogeneic transplant. We extended the combined end- points of disease-free and overall survival to competing-risk settings: dis- ease-free survival was split into relapse and non-relapse mortality. Overall survival was divided into transplant-related mortality, death from other causes and death from unknown causes. For time-dependent effects we computed estimators before and after a covariable-specific cut- point. Patients treated with reduced intensity conditioning had a con- stantly higher risk of relapse compared to patients treated with myeloab- lative conditioning. For non-relapse mortality, patients treated with reduced intensity conditioning had a reduced mortality risk but this effect was only seen in the first 4 months after transplantation (hazard ratio: 0.76, P<0.001) and not afterwards. Graft source exhibited a time-depen- dent effect on both transplant-related mortality (in first year: hazard ratio 0.70, P<0.001; after first year: hazard ratio 1.47, P=0.002) and non-relapse mortality (in first 8 months: hazard ratio 0.75, P<0.001; after first 8 months: hazard ratio 1.38, P<0.001). Patients with a poor Karnofsky per- formance score (<80) had a considerably higher risk of all endpoints in the first 4 months. The competing-risk analysis for overall survival and disease-free survival allows resolution of effects with different vectors early and later after stem cell transplantation, as shown for graft source. This information may be useful in risk assessment of treatment choices and for counseling patients on an individual basis.
Correspondence:
j.mytilineos@blutspende.de
Received: October 20, 2017. Accepted: May 30, 2018. Pre-published: June 7, 2018.
doi:10.3324/haematol.2017.183012
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/9/1527
©2018 Ferrata Storti Foundation
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haematologica | 2018; 103(9)
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