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J Allergy Clin Immunol. 2014 Oct;134(4):935-943.e15. doi: 10.1016/j.jaci.2014.06.021. Epub 2014 Aug 7.

Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency.

Author information

  • 1Division 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.
  • 2Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom.
  • 3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • 4Department of Pediatrics, University Medical Center, Ulm, Germany.
  • 5Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
  • 6Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC.
  • 7Division of Hematology and Hematologic Malignancies, Primary Children's Hospital, University of Utah School of Medicine/Huntsman Cancer Institute, Salt Lake City, Utah.
  • 8Hematology/Oncology/BMT Program, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
  • 9University Children's Hospital, Stem Cell Transplantation Department, Zurich, Switzerland.
  • 10Oncology Department, The Children's Hospital at Westmead, Westmead, Australia.
  • 11Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
  • 12Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa.
  • 13Department of Pediatric Hematology and Oncology, Teaching Hospital Motol, Prague, Czech Republic.
  • 14Division of Pediatric Hematology-Oncology, University of Michigan, Ann Arbor, Mich.
  • 15Department of Pediatrics, University of Oklahoma, Oklahoma City, Okla.
  • 16Division of Immunology and The Manton Center for Orphan Disease Research, Children's Hospital Boston, Harvard Medical School, Boston, Mass.
  • 17Division of Hematology and Oncology, Boston Children's Hospital, and the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass.
  • 18Division 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.

Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Severe combined immunodeficiency; conditioning; hematopoietic cell transplantation; serotherapy; sibling donors; umbilical cord blood; unrelated donors

PMID:
25109802
[PubMed - indexed for MEDLINE]
PMCID:
PMC4186906
Free PMC Article
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