title: Time-dependent effects of clinical predictors in unrelated hematopoietic stem cell transplantation.
abstract: Hematopoietic stem cell transplantation is a multifactorial process. Some of the predictors exhibit time-dependent effects. We present a systematic analysis and description of selected clinical predictors influencing outcome in a time-dependent manner based on an analysis of registry data from the German Registry for Stem Cell Transplantation. A total of 14,951 patients with acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome and non-Hodgkin lymphoma transplanted with peripheral blood stem cells or bone marrow grafts were included. Multivariate Cox regression models were tested for time-dependent effects within each diagnosis group. Predictors not satisfying the proportional hazards assumption were modeled in a time-dependent manner, extending the Cox regression models. Similar patterns occurred in all diagnosis groups. Patients with a poor Karnofsky performance score (<80) had a high risk for early mortality until day 139 following transplantation (HR 2.42, CI: 2.19-2.68; P<0.001) compared to patients with a good Karnofsky performance score (80-100). Afterwards the risk reduced to HR 1.43, CI: 1.25-1.63; P<0.001. A lower mortality risk was found for patients after conditioning treatment with reduced intensity until day 120 post transplant (HR: 0.81 CI: 0.75-0.88; P<0.001). After this, a slightly higher risk could be shown for these patients. Similarly, patients who had received a PBSC graft exhibited a significantly lower mortality risk until day 388 post transplantation (HR 0.79, CI: 0.73-0.85; P<0.001), reversing to a significantly higher risk afterwards (HR 1.23, CI: 1.08-1.40; P=0.002). Integrating time dependency in regression models allows a more accurate description and quantification of clinical predictors to be made, which may help in risk assessment and patient counseling.
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German, Red Cross Blood Transfusion Service, Baden-Wuerttemberg - Hessen, Ulm, Germany Institute of Transfusion Medicine, University of Ulm, Ulm, Germany d.fuerst@blutspende.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fuerst
authors.affiliation: DRST - German Registry for Stem Cell Transplantation, Ulm Office, Ulm, Germany Zentrales Knochenmarkspender-Register Deutschland (ZKRD), Ulm, Germany.
authors.forename: Carlheinz
authors.initials: C
authors.lastname: Mueller
authors.affiliation: DRST - German Registry for Stem Cell Transplantation, Essen Office, Essen, Germany Department of Bone Marrow Transplantation, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German, Red Cross Blood Transfusion Service, Baden-Wuerttemberg - Hessen, Ulm, Germany Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Neuchel
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German, Red Cross Blood Transfusion Service, Baden-Wuerttemberg - Hessen, Ulm, Germany Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Tsamadou
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German, Red Cross Blood Transfusion Service, Baden-Wuerttemberg - Hessen, Ulm, Germany Institute of Transfusion Medicine, University of Ulm, Ulm, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German, Red Cross Blood Transfusion Service, Baden-Wuerttemberg - Hessen, Ulm, Germany Institute of Transfusion Medicine, University of Ulm, Ulm, Germany DRST - German Registry for Stem Cell Transplantation, Ulm Office, Ulm, Germany.
authors.forename: Joannis
authors.initials: J
authors.lastname: Mytilineos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D005858:Germany; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D012306:Risk; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents