185 B Cell Engraftment in SCID Patients After Stem Cell Transplantation

Track: Contributed Abstracts
Wednesday, February 13, 2013, 6:45 PM-7:45 PM
Hall 1 (Salt Palace Convention Center)
Caridad Martinez, MD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
William Shearer, MD, PhD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Sarah K Nicholas, MD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Jordan Orange, MD, PhD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Javier Chinen, MD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Howard Rosenblatt, MD , Department Allergy, Asthma, Immunology, Dell Children's Medical Center and SFC
Jesse Wu, PhD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Catherine M. Bollard, MD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Kathryn Leung, MD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Malcolm K. Brenner, MD, PhD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Helen E Heslop, MD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Imelda C Hanson, MD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Robert A. Krance, MD , Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Stem cell transplantation (SCT) is the only curative option for patients (pts) with Severe combined immunodeficiency (SCID). Adequate T cell function is usually achieved in these pts after SCT. Unfortunately, however, adequate B cell function often fails, and little is known about how disease type, conditioning or stem cell graft  influence this process. We report  B cell function reconstitution following SCT (1998-2012) in 35 SCID pts: IL2RG (n=13), JAK3 (n=2), RAG1, 2 (n=2), IL7RA (n=5), CD3D (n=4), Zap70 (n=2), MHCII def (n=1), ADA (n=2), and not differentiated (n=4). Fourteen pts received a haploidentical donor graft, 8 pts a matched related donor (MRD) graft, 7 pts a matched/mismatched unrelated donor (MUD/MMUD) graft, and 7 pts a mismatched unrelated cord blood (MMUCB) graft.  One pt received a MMUCB after a haploidentical graft failure. 23 pts underwent ablative conditioning with busulfan, cyclophosphamide, and fludarabine or cytarabine, 7 pts a reduced intensity conditioning using fludarabine and anti-CD52 and/or anti-CD45. Five pts were not conditioned. Anti-CD52 was used in 22 pts. MMUCB recipients receive no serotherapy. Overall survival of the entire cohort was 87% with a median follow up of 6 years (range, 0.5 -13 years); MRD and MMUCB graft recipients had a 100% survival. To determine functional B cell engraftment we measured IgA and total IgG. Engraftment was considered successful when IgA was normal and levels of IgG were above 500 mg/dL without supplemental IVIG. Adequate B cell function of the whole group occurred at a median time of 4 years (range, 2-13 years) in the haploidentical and MRD recipients, at 3 years (range, 2-6 years) in the MUD/MMUD recipients and at just 6 months (range, 4-11 months) in the MMUCB recipients. Five of 28 evaluable patients (3/14 haplo and 2/8 MUD) failed to achieve adequate B cell function and are still dependent on IVIG infusions.  All 5 patients with absence of B cell function had less than 25% B cell donor engraftment and 3 of them had received ablative conditioning. Less than 25% donor B cell engraftment correlated with abscense of function (p=0.006). 4/5 patients with absent B cell function have IL2RG genetic defect (OR=5.12, p=0.038).  All the recipients of MMUCB achieved faster and more reliable B cell function compared to other donor sources (p=0.003). Hence absence of adequate B cell function is most closely associated with pts who have IL2RG defect irrespective of conditioning. In addition, donor source influence the speed and probably the ultimate success of B cell engraftment (MMUCB>haplo donors).
See more of: Poster Session 1: Immune Reconstitution
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