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Retrospective Study of 240 Patients with Severe Combined Immunodeficiency Transplanted from 2000-2009: A Report from the Primary Immune Deficiency Treatment Consortium of North America

Track: BMT Tandem "Scientific" Meeting
Friday, February 28, 2014, 4:45 PM-6:30 PM
Texas B+D (Gaylord Texan)
Sung-Yun Pai, MD , Hematology-Oncology, Boston Children's Hospital, Boston, MA
Brent R. Logan, PhD , Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI
Linda M Griffith, MD, PhD , DAIT, NIAID, NIH, Bethesda, MD
Rebecca H Buckley, MD , Duke University Medical Center, Durham, NC
Roberta E Parrott, BS , Duke University Medical Center, Durham, NC
Christopher C. Dvorak, MD , University of California San Francisco Medical Center, San Francisco, CA
Neena Kapoor, MD , Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, CA
Imelda C Hanson, MD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Alexandra Filipovich, MD , Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Soma Jyonouchi, MD , Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA
Trudy Small, MD , Department of Pediatrics, Pediatric Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Lauri Burroughs, MD , Fred Hutchinson Cancer Research Center, Seattle, WA
Ann E Haight, MD , Aflac Cancer Center and Blood Disorders Service, Emory / Children's Healthcare of Atlanta, Atlanta, GA
Michael A. Pulsipher, MD , Primary Children's Medical Center, University of Utah School of Medicine, Salt Lake City, UT
Ka Wah Chan, MD , Pediatric Blood and Marrow Stem Cell Transplant, Texas Transplant Institute, San Antonio, TX
Ramsay Fuleihan, MD , Allergy and Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
Elie Haddad, MD PhD , Paediatric Immunology, Ste-Justine Hospital, Montreal, QC, Canada
Brett Loechelt, MD , Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC
Victor Aquino, MD , Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX
Alfred P. Gillio, MD , Ped. Heme Onc, HUMC, Hackensack, NJ
Jeffrey H Davis, MD , Pediatrics, British Columbia Children's Hospital, Vancouver, BC, Canada
Alan Knutsen, MD , Pediatric Allergy & Immunology, Cardinal Glennon Children's Medical Center, St. Louis, MO
Angela Smith, MD, MS , Pediatric Hematology/Oncology/Blood and Marrow Transplantation, University of Minnesota Medical Center, Fairview, Minneapolis, MN
Theodore B Moore, MD , Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA
Marlis Schroeder, MD , Pediatric BMT Program, CancerCare Manitoba, Winnipeg, MB, Canada
Frederick Goldman, MD , Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL
James A Connelly, MD , Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI
Matthew H. Porteus, MD , Pediatric Stem Cell Transplantation, Stanford University, Palo Alto, CA
Qun Xiang, MS , Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI
William Shearer, MD, PhD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Thomas Fleisher, MD , Laboratory of Host Defenses, National Institutes of Health, Bethesda, MD
Donald B. Kohn, MD , Department of Microbiology, Immunology and Molecular Genetics and Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA
Jennifer Puck, MD , Pediatric Allergy Immunology and Blood and Marrow Transplant Division, UCSF Benioff Children's Hospital, San Francisco, CA
Luigi D. Notarangelo, MD , Program on Primary Immunodeficiencies, Children’s Hospital Boston, Harvard Medical School, Boston, MA
Morton J Cowan, MD , Pediatric Allergy Immunology and Blood and Marrow Transplant Division, UCSF Benioff Children's Hospital, San Francisco, CA
Richard O'Reilly, MD , Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY

The Primary Immune Deficiency Treatment Consortium (PIDTC) conducted a retrospective study of 240 SCID patients transplanted at 25 consortium centers from 2000-2009. Patients with a diagnosis of typical SCID, as defined by recently published PIDTC consensus criteria, who underwent allogeneic HCT were included after central review. Leaky SCID and Omenn syndrome were excluded. Donors included matched sibling (MSD), T-cell depleted (TCD) mismatched related (MMRD), and unmodified other related/unrelated donors (OD). Cell sources included bone marrow (BM), peripheral blood (PB) and umbilical cord blood (UCB) (See Table). The vast majority of MSD and TCD MMRD HCT were performed without conditioning and the rest were divided between those receiving immunosuppression (IS, no busulfan, thiotepa or melphalan), reduced intensity (RIC, containing alkylating agents equivalent to <12 mg/kg busulfan) and myeloablative conditioning (MAC, equivalent to = or >12 mg/kg busulfan). The overall 5-year survival (OS) rate was 74% (178/240). Multivariate analysis of OS revealed superior outcomes for MSD when compared to TCD MMRD or unmodified OD grafts (Fig. 1A). However, irrespective of the type of transplant administered, patients age <3.5 months and patients of any age who were free of infection at HCT, all had excellent OS, similar to MSD (OS 88-100%) (Fig. 1B-E). Thus, freedom from infection at HCT had a central role in outcomes of non-MSD HCT for SCID. Conditioning with RIC/MAC did not affect survival (Fig. 1F). RIC/MAC also did not influence donor T cell engraftment in MSD recipients, who had the lowest rate of 2nd transplant (6.3%) despite lack of conditioning, nor in non-MSD recipients (2nd transplant none/IS 23% vs. RIC/MAC 16%). However, while 92% of all patients tested had normal T cell responses to mitogens, the likelihood of T cell recovery (CD3+ >1000/ul) was significantly enhanced by RIC/MAC. Donor type and genetic subtype of SCID also influenced T-cell recovery following non-MSD HCT. Humoral immunity was consistently achieved post MSD HCT despite lack of conditioning; for patients who received non-MSD HCT, IVIG independence was much more likely in those who received RIC/MAC (84.6% vs. 28.2%, p<0.001). Our study indicates that all transplant types analyzed can result in excellent survival when applied to infants with SCID identified early, before onset of infections, underscoring the critical importance of universal newborn screening for SCID. While the use of RIC/MAC in non-MSD recipients led to improvements in some aspects of immune recovery, the risks of adverse effects on development, neurocognition, and fertility remain a concern, and illustrate the need for less toxic regimens.

Total (240)

MSD (32)

MMRD-TCD (138)

Other related (8)

Unrelated (62)

Graft type

BM

139

31

85

8

15

PB

58

1

53

0

4

UCB

43

0

0

0

43

Conditioning regimen

None

120

21

87

6

6

IS

39

7

16

1

15

RIC

35

2

10

1

22

MAC

46

2

25

0

19

Disclosures:
Nothing To Disclose
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