93 The Natural History of Children with Severe Combined Immunodeficiency Disease - the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium (PIDTC) Prospective Study 6901

Track: Pediatric BMT Program
Thursday, February 14, 2013, 5:15 PM-6:45 PM
155 A-F (Salt Palace Convention Center)
Christopher C Dvorak, MD , Pediatric Allergy Immunology and Blood and Marrow Transplant Division, UCSF Benioff Children's Hospital, San Francisco, CA
Morton J Cowan, MD , Pediatric Allergy Immunology and Blood and Marrow Transplant Division, UCSF Benioff Children's Hospital, San Francisco, CA
Brent R. Logan, PhD , Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI
Linda Griffith, MD, PhD , Dait, Niaid, Nih, Bethesda, MD
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
Donald B. Kohn, MD , Department of Microbiology, Immunology and Molecular Genetics and Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA
Qun Xiang, MS , Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI
Mary Eapen, MD, MS , CIBMTR, Medical College of Wisconsin, Milwaukee, WI
William Shearer, MD, PhD , Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Michael A. Pulsipher, MD , Division of Hematology and Hematologic Malignancies, Primary Children's Medical Center/Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT
Rebecca Buckley, MD , Duke University Medical Center, Durham, NC

The PIDTC consists of 32 centers in North America that care for patients with PID. The 6901 study's hypothesis is that the analysis of uniform data on patients with SCID will identify those variables that contribute to the best outcomes following treatment. We report baseline clinical, immunologic & genetic features of the 1st 50 patients enrolled & the initial therapies that they received, to summarize for the first time the current practice in the diagnosis & treatment of SCID. 

From 8/2010 - 5/2012 patients with suspected SCID underwent work-up and therapy per local center practices. After consent, diagnostic information was reviewed by the eligibility and stratification panel. Stratum A is classic SCID. Stratum B is leaky SCID, Omenn Syndrome or Reticular Dysgenesis. HCT details were obtained from the CIBMTR.

Presenting features of the 1st 50 patients are shown (Table). 92% had mutations in a known SCID gene. Those diagnosed by newborn screen (NBS) or family history (FH) were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001) and went to HCT at a median of 67 days vs. 214 days (P = <0.0001), though there was no difference in time from diagnosis to HCT (median 56 vs. 43 days; P = 0.28). 92% were treated with HCT at a median of 25 days from diagnosis for matched related (n = 7) or 29 days mismatched related (n = 12) donors, vs. 61 days for unrelated adult (n = 13) or 60 days for cord blood (n = 14) donors (P = 0.02). Conditioning was none (n = 10), serotherapy alone (n = 4); reduced intensity (n = 9), or myeloablative (n = 23). 3 patients were treated with gene therapy & 1 with enzyme-replacement.

Future directions include continued enrollment with a goal of >250 patients & analysis of short and long-term outcomes of therapy to identify which factors are beneficial or deleterious to survival, T- and B-cell reconstitution & clinical outcome after treatment for SCID & what biomarkers are predictive of these outcomes.

Table: Features at Diagnosis

Stratum A

Stratum B

n = 37

n = 13

Age, days

34 (0 - 304)

74 (0 - 4916)

Gender (M / F)

28 / 9

4 / 9

Trigger of Dx

   FH

27%

15%

   NBS

32%

8%

   Infection

38%

54%

   Other

3%

23%

Maternal Engraftment

53%

0%

Autoimmunity

3%

42%

FTT

24%

33%

ALC

1175 (3 - 10120)

1078 (700- 3700)

CD3

6 (0-8898)

1918 (45 - 6589)

   CD4

4 (0 - 1307)

474 (31 - 2138)

      CD4/CD45RA

0 (0 - 57)

43 (0 - 474)

      CD4/CD45RO

1 (0 - 155)

1035 (196 - 1975)

   CD8

4 (0 - 750)

78 (0 - 900)

   PHA (% lower limit nl)

0 (0 - 20)

12 (0 - 126)

   TRECs (#/uL)

0 (0 - 11)

0

B Cells: B+ Phenotype

1171 (164 - 3847); n = 29

2 (0 - 822)

              B- Phenotype

7 (0 - 186); n = 8

   IgG (mg/dL), pre-IVIG

539 (0 - 928)

608 (371 - 1030)

   IgM (mg/dL)

10 (0 - 89)

13 (0 - 95)

   IgA (mg/dL)

7 (0 - 25)

7 (0 - 165)

   IgE (IU/mL)

2 (0 - 79)

445 (0 - 20400)

NK Cells: NK+ Phenotype

266 (28 - 939); n = 12

282 (32 - 734)

                 NK- Phenotype

16 (0 - 407); n = 25

IL-2RG

19

0

JAK3

2

1

RAG-1/2

5

7

Artemis

0

1

IL-7R

3

0

CD3d

3

0

ADA

3

0

AK2

0

1

Unknown

1

3

Numbers = median (range); Cells = (x 106/L)

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