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


Dvorak, Christopher C; Hassan, Amel; Slatter, Mary A; Hönig, Manfred; Lankester, Arjan C; Buckley, Rebecca H; Pulsipher, Michael A; Davis, Jeffrey H; Güngör, Tayfun; Gabriel, Melissa; Bleesing, Jacob H; Bunin, Nancy; Sedlacek, Petr; Connelly, James A; Crawford, David F; Notarangelo, Luigi D; Pai, Sung-Yun; Hassid, Jake; Veys, Paul; Gennery, Andrew R; Cowan, Morton J (2014). Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. Journal of Allergy and Clinical Immunology, 134(4):935-943.e15.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:October 2014
Deposited On:11 Feb 2015 09:35
Last Modified:05 Mar 2017 06:38
Publisher:Elsevier
ISSN:0091-6749
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jaci.2014.06.021
PubMed ID:25109802

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