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J Allergy Clin Immunol. 2016 Oct;138(4):1152-1160. doi: 10.1016/j.jaci.2016.01.053. Epub 2016 Apr 20.

Effect of stem cell source on long-term chimerism and event-free survival in children with primary immunodeficiency disorders after fludarabine and melphalan conditioning regimen.

Author information

1
Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom. Electronic address: kanchan.rao@gosh.nhs.uk.
2
Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom.
3
Department of Blood and Marrow Transplantation, Great Ormond Street Hospital for Children, London, United Kingdom; Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom.

Abstract

BACKGROUND:

Reduced-intensity conditioning (RIC) regimens are increasingly being used in the transplantation of patients with primary immunodeficiency disorders (PIDs), but there are no large studies looking at long-term lineage-specific chimerism.

OBJECTIVES:

We sought to analyze long-term chimerism and event-free survival in children undergoing transplantation for PIDs using RIC with fludarabine and melphalan (Flu/Melph) and to study the effect of donor type and stem cell source.

METHODS:

One hundred forty-two children underwent transplantation with RIC by using Flu/Melph and for PIDs by using bone marrow (n = 93) or peripheral blood stem cells (PBSCs; n = 49). Donors were matched unrelated donors (n = 72), mismatched unrelated donors (n = 37), matched sibling donors (n = 14), matched family donors (n = 12), and mismatched family donors (n = 7).

RESULTS:

Overall survival at a median follow-up of 7.5 years was 78%, irrespective of stem cell source or donor type. When bone marrow was used as the stem cell source, 26% of patients ended up with very low levels of donor chimerism (<10% donor), especially in the myeloid lineage. Event-free survival in this group was significantly lower compared with that in the rest of the group (25% vs 70%, P < .001). With the use of PBSCs, more than 90% of patients achieved complete donor chimerism or high-level mixed chimerism (>50% donor chimerism) in all lineages.

CONCLUSIONS:

On the basis of our experience, we would suggest that PBSCs should be the stem cell source of choice in children with PIDs undergoing transplantation with Flu/Melph RIC from a matched donor source. This is most likely to ensure sustained high-level donor chimerism.

KEYWORDS:

Primary immunodeficiency disorder; chimerism; hematopoietic stem cell transplantation; lineage specific; reduced intensity

PMID:
27241891
DOI:
10.1016/j.jaci.2016.01.053
[Indexed for MEDLINE]

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