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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Lineage
  • Chimerism*
  • Disease-Free Survival*
  • Drug Therapy, Combination
  • Follow-Up Studies
  • Humans
  • Immunologic Deficiency Syndromes / drug therapy
  • Immunologic Deficiency Syndromes / mortality
  • Immunologic Deficiency Syndromes / therapy*
  • Infant
  • Infant, Newborn
  • Melphalan / therapeutic use*
  • Stem Cell Transplantation / standards*
  • Stem Cells / cytology*
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use


  • Vidarabine
  • fludarabine
  • Melphalan