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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Rao, Kanchan¹  Adams, Stuart¹  Qasim, Waseem^1,2  Allwood, Zoe¹  Worth, Austen^1,2  Silva, Juliana¹  Lucchini, Giovanna¹  Chiesa, Robert¹  Veys, Paul¹  Amrolia, Persis^1,2 

[1] Great Ormond St Hosp Sick Children, Dept Blood & Marrow Transplantat, London, England

[2] UCL, Inst Child Hlth, Mol Immunol Unit, London WC1E 6BT, England

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

DOI  :  10.1016/j.jaci.2016.01.053

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free