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

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.

• Authors: Christopher C Dvorak, Amel Hassan, Mary A Slatter, Manfred Hönig, Arjan C Lankester, Rebecca H Buckley, Michael A Pulsipher, Jeffrey H Davis, Tayfun Güngör, Melissa Gabriel, Jacob H Bleesing, Nancy Bunin, Petr Sedlacek, James A Connelly, David F Crawford, Luigi D Notarangelo, Sung-Yun Pai, Jake Hassid, Paul Veys, Andrew R Gennery, Morton J Cowan
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 134 Issue 4 Pg. 935-943.e15 (Oct 2014) ISSN: 1097-6825 [Electronic] United States
• PMID: 25109802 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Topics

• Adult
• Australia
• B-Lymphocytes (immunology)
• Child
• Chimerism
• Europe
• Female
• Graft vs Host Disease (etiology, prevention & control)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility
• Histocompatibility Testing
• Humans
• Infant
• Infant, Newborn
• Male
• North America
• Retrospective Studies
• Severe Combined Immunodeficiency (diagnosis, mortality, therapy)
• Siblings
• Survival Analysis
• T-Lymphocytes (immunology)
• Transplantation Conditioning
• Treatment Outcome
• Unrelated Donors
• Volunteers