Christopher C Dvorak1, Amel Hassan2, Mary A Slatter3, Manfred Hönig4, Arjan C Lankester5, Rebecca H Buckley6, Michael A Pulsipher7, Jeffrey H Davis8, Tayfun Güngör9, Melissa Gabriel10, Jacob H Bleesing11, Nancy Bunin12, Petr Sedlacek13, James A Connelly14, David F Crawford15, Luigi D Notarangelo16, Sung-Yun Pai17, Jake Hassid18, Paul Veys2, Andrew R Gennery3, Morton J Cowan18. 1. Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif. Electronic address: dvorakc@peds.ucsf.edu. 2. Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom. 3. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. 4. Department of Pediatrics, University Medical Center, Ulm, Germany. 5. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. 6. Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC. 7. Division of Hematology and Hematologic Malignancies, Primary Children's Hospital, University of Utah School of Medicine/Huntsman Cancer Institute, Salt Lake City, Utah. 8. Hematology/Oncology/BMT Program, British Columbia Children's Hospital, Vancouver, British Columbia, Canada. 9. University Children's Hospital, Stem Cell Transplantation Department, Zurich, Switzerland. 10. Oncology Department, The Children's Hospital at Westmead, Westmead, Australia. 11. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. 12. Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa. 13. Department of Pediatric Hematology and Oncology, Teaching Hospital Motol, Prague, Czech Republic. 14. Division of Pediatric Hematology-Oncology, University of Michigan, Ann Arbor, Mich. 15. Department of Pediatrics, University of Oklahoma, Oklahoma City, Okla. 16. Division of Immunology and The Manton Center for Orphan Disease Research, Children's Hospital Boston, Harvard Medical School, Boston, Mass. 17. Division of Hematology and Oncology, Boston Children's Hospital, and the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass. 18. Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
Abstract
BACKGROUND: Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. OBJECTIVE: We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. METHODS: We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). RESULTS: Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). CONCLUSION: Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.
BACKGROUND:Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. OBJECTIVE: We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs. METHODS: We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66). RESULTS: Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001). CONCLUSION: Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.
Authors: E Haddad; P Landais; W Friedrich; B Gerritsen; M Cavazzana-Calvo; G Morgan; Y Bertrand; A Fasth; F Porta; A Cant; T Espanol; S Müller; P Veys; J Vossen; A Fischer Journal: Blood Date: 1998-05-15 Impact factor: 22.113
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Authors: Jennifer Heimall; Jennifer Puck; Rebecca Buckley; Thomas A Fleisher; Andrew R Gennery; Benedicte Neven; Mary Slatter; Elie Haddad; Luigi D Notarangelo; K Scott Baker; Andrew C Dietz; Christine Duncan; Michael A Pulsipher; Mort J Cowan Journal: Biol Blood Marrow Transplant Date: 2017-01-06 Impact factor: 5.742
Authors: Alexandra M Miggelbrink; Brent R Logan; Rebecca H Buckley; Roberta E Parrott; Christopher C Dvorak; Neena Kapoor; Hisham Abdel-Azim; Susan E Prockop; David Shyr; Hélène Decaluwe; Imelda C Hanson; Alfred Gillio; Blachy J Dávila Saldaña; Hermann Eibel; Gregory Hopkins; Jolan E Walter; Jennifer S Whangbo; Donald B Kohn; Jennifer M Puck; Morton J Cowan; Linda M Griffith; Elie Haddad; Richard J O'Reilly; Luigi D Notarangelo; Sung-Yun Pai Journal: Blood Date: 2018-05-04 Impact factor: 22.113
Authors: C C Dvorak; K Patel; J M Puck; J Wahlstrom; M J Dorsey; R Adams; J Facchino; M J Cowan Journal: Bone Marrow Transplant Date: 2017-04-24 Impact factor: 5.483