Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time-dependent effects
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Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time-dependent effects. / Fuerst, Daniel; Frank, Sandra; Mueller, Carlheinz; Beelen, Dietrich W; Schetelig, Johannes; Niederwieser, Dietger; Finke, Jürgen; Bunjes, Donald; Kröger, Nicolaus; Neuchel, Christine; Tsamadou, Chrysanthi; Schrezenmeier, Hubert; Beyersmann, Jan; Mytilineos, Joannis.
In: HAEMATOLOGICA, Vol. 103, No. 9, 09.2018, p. 1527-1534.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time-dependent effects
AU - Fuerst, Daniel
AU - Frank, Sandra
AU - Mueller, Carlheinz
AU - Beelen, Dietrich W
AU - Schetelig, Johannes
AU - Niederwieser, Dietger
AU - Finke, Jürgen
AU - Bunjes, Donald
AU - Kröger, Nicolaus
AU - Neuchel, Christine
AU - Tsamadou, Chrysanthi
AU - Schrezenmeier, Hubert
AU - Beyersmann, Jan
AU - Mytilineos, Joannis
N1 - Copyright © 2018, Ferrata Storti Foundation.
PY - 2018/9
Y1 - 2018/9
N2 - The success of hematopoietic stem cell transplantation is determined 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 endpoints of disease-free and overall survival to competing-risk settings: disease-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 constantly higher risk of relapse compared to patients treated with myeloablative 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-dependent 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 performance 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.
AB - The success of hematopoietic stem cell transplantation is determined 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 endpoints of disease-free and overall survival to competing-risk settings: disease-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 constantly higher risk of relapse compared to patients treated with myeloablative 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-dependent 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 performance 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.
KW - Journal Article
U2 - 10.3324/haematol.2017.183012
DO - 10.3324/haematol.2017.183012
M3 - SCORING: Journal article
C2 - 29880610
VL - 103
SP - 1527
EP - 1534
JO - HAEMATOLOGICA
JF - HAEMATOLOGICA
SN - 0390-6078
IS - 9
ER -
