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

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• 作者：Kanchan Rao ; MRCPCH ; MNAMS^a ; ^{kanchan.rao@gosh.nhs.uk" class="auth_mail" title="E-mail the corresponding author} ; Stuart Adams ; PhD^a ; Waseem Qasim ; MD ; PhD^a ; ^b ; Zoe Allwood ; BSc ; MPH^a ; Austen Worth ; MRCP ; MD ; PhD^a ; ^b ; Juliana Silva ; MD^a ; Giovanna Lucchini ; MD^a ; Robert Chiesa ; MD^a ; Paul Veys ; FRCP ; FRCPath^a ; Persis Amrolia ; PhD ; FRCP ; FRCPath^a ; ^b
• 关键词：Primary immunodeficiency disorder ; hematopoietic stem cell transplantation ; chimerism ; lineage specific ; reduced intensity
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：138
• 期：4
• 页码：1152-1160
• 全文大小：1086 K

文摘

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.