title: Multi-state analysis illustrates treatment success after stem cell transplantation for acute myeloid leukemia followed by donor lymphocyte infusion.
abstract: In the field of hematopoietic stem cell transplantation, the common approach is to focus outcome analyses on time to relapse and death, without assessing the impact of post-transplant interventions. We investigated whether a multi-state model would give insight into the events after transplantation in a cohort of patients who were transplanted using a strategy including scheduled donor lymphocyte infusions. Seventy-eight consecutive patients who underwent myeloablative T-cell depleted allogeneic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome were studied. We constructed a multi-state model to analyze the impact of donor lymphocyte infusion and graft-versus-host disease on the probabilities of relapse and non-relapse mortality over time. Based on this model we introduced a new measure for outcome after transplantation which we called 'treatment success': being alive without relapse and immunosuppression for graft-versus-host disease. All relevant clinical events were implemented into the multi-state model and were denoted treatment success or failure (either transient or permanent). Both relapse and non-relapse mortality were causes of failure of comparable magnitude. Whereas relapse was the dominant cause of failure from the transplantation state, its rate was reduced after graft-versus-host disease, and especially after donor lymphocyte infusion. The long-term probability of treatment success was approximately 40%. This probability was increased after donor lymphocyte infusion. Our multi-state model helps to interpret the impact of post-transplantation interventions and clinical events on failure and treatment success, thus extracting more information from observational data.
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eefting
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, the Netherlands l.c.de_wreede@lumc.nl.
authors.forename: Liesbeth C
authors.initials: LC
authors.lastname: de Wreede
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: Constantijn J M
authors.initials: CJ
authors.lastname: Halkes
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: von dem Borne
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: Sabina
authors.initials: S
authors.lastname: Kersting
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: Erik W A
authors.initials: EW
authors.lastname: Marijt
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, the Netherlands.
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.affiliation: Medical Department I, University Hospital Carl Gustav Carus, Technische Universität Dresden & DKMS, German Bone Marrow Donor Center, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.affiliation: Department of Hematology, Leiden University Medical Center, the Netherlands.
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D019653:Myeloablative Agonists / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D035781:Siblings; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D019653:Myeloablative Agonists