Roni Shouval1, Joshua A Fein2, Myriam Labopin3, Nicolaus Kröger4, Rafael F Duarte5, Peter Bader6, Christian Chabannon7, Jurgen Kuball8, Grzegorz Wladyslaw Basak9, Carlo Dufour10, Jacques-Emmanuel Galimard3, Emmanuelle Polge3, Arjan Lankester11, Silvia Montoto12, John A Snowden13, Jan Styczynski14, Ibrahim Yakoub-Agha15, Mohamad Mohty16, Arnon Nagler17. 1. Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Israel; Dr Pinchas Bornstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Ramat-Gan, Israel. 2. Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Israel. 3. Acute Leukemia Working Party, Paris Study office, European Society for Blood and Marrow Transplantation, Paris, France; Clinical Hematology and Cellular Therapy, Hopital Saint-Antoine, Université Pierre & Marie Curie, Paris, France. 4. Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany. 5. Hematology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. 6. Department for Children and Adolescents, Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, University Hospital Frankfurt, Frankfurt, Germany. 7. Département de Biologie du Cancer, Institut Paoli-Calmettes, Inserm CBT-1409, Aix-Marseille Université, Marseille, France. 8. Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands. 9. Department of Hematology, Oncology and Internal Medicine, University Clinical Centre, Medical University of Warsaw, Warsaw, Poland. 10. Hematology Unit, IRCSS G Gaslini Children's Hospital, Genova, Italy. 11. Department of Pediatrics, Leiden University Medical Centre, Leiden, Netherlands. 12. Department of Haemato-Oncology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK. 13. Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. 14. Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland. 15. Department of Haematology, CHU de Lille, LIRIC, INSERM U995, Universite de Lille, Lille, France. 16. Clinical Hematology and Cellular Therapy, Hopital Saint-Antoine, Université Pierre & Marie Curie, Paris, France. 17. Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Israel. Electronic address: arnon.nagler@sheba.health.gov.il.
Abstract
BACKGROUND: The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. METHODS: In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. FINDINGS: We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7-7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1-54·8] to 54·6% [53·6-55·6]; matched unrelated: 49·1% [48·0-50·2] to 51·6% [50·7-52·6]; mismatched unrelated: 37·4% [35·7-39·2] to 41·3% [39·5-43·1]; haploidentical: 34·5% [31·4-37·9] to 44·2% [42·1-46·3]; and cord blood 36·3% [33·9-39] to 43·7% [40·8-46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. INTERPRETATION: Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. FUNDING: The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.
BACKGROUND: The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. METHODS: In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. FINDINGS: We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7-7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1-54·8] to 54·6% [53·6-55·6]; matched unrelated: 49·1% [48·0-50·2] to 51·6% [50·7-52·6]; mismatched unrelated: 37·4% [35·7-39·2] to 41·3% [39·5-43·1]; haploidentical: 34·5% [31·4-37·9] to 44·2% [42·1-46·3]; and cord blood 36·3% [33·9-39] to 43·7% [40·8-46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. INTERPRETATION: Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. FUNDING: The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.
Authors: Olaf Penack; Christophe Peczynski; Mohamad Mohty; Ibrahim Yakoub-Agha; Jan Styczynski; Silvia Montoto; Rafael F Duarte; Nicolaus Kröger; Hélène Schoemans; Christian Koenecke; Zinaida Peric; Grzegorz W Basak Journal: Blood Adv Date: 2020-12-22
Authors: Emma E Ilett; Mette Jørgensen; Marc Noguera-Julian; Jens Christian Nørgaard; Gedske Daugaard; Marie Helleberg; Roger Paredes; Daniel D Murray; Jens Lundgren; Cameron MacPherson; Joanne Reekie; Henrik Sengeløv Journal: Blood Adv Date: 2020-11-24
Authors: Alexandra Gomez-Arteaga; Nina Orfali; Danielle Guarneri; Melissa M Cushing; Usama Gergis; Jingmei Hsu; Yen-Michael S Hsu; Sebastian A Mayer; Adrienne A Phillips; Stacy A Chase; Asmaa E Mokhtar; Tsiporah B Shore; Koen Van Besien Journal: Bone Marrow Transplant Date: 2020-06-09 Impact factor: 5.483