Immune Reconstitution and Survival of 100 SCID Patients Post Hematopoietic Cell Transplant: A PIDTC Natural History Study.

Heimall, Jennifer

Logan, Brent R

Cowan, Morton J

Notarangelo, Luigi D

Griffith, Linda M

Puck, Jennifer M

Kohn, Donald B

Pulsipher, Michael A

Parikh, Suhag

Martinez, Caridad

Kapoor, Neena

O'Reilly, Richard

Boyer, Michael

Pai, Sung-Yun

Goldman, Frederick

Burroughs, Lauri

Chandra, Sharat

Kletzel, Morris

Thakar, Monica

Connelly, James

Cuvelier, Geoff

Davila Saldana, Blachy J

Shereck, Evan

Knutsen, Alan

Sullivan, Kathleen E

DeSantes, Kenneth

Gillio, Alfred

Haddad, Elie

Petrovic, Aleksandra

Quigg, Troy

Smith, Angela R

Stenger, Elizabeth

Yin, Ziyan

Shearer, William T

Fleisher, Thomas

Buckley, Rebecca H

Dvorak, Christopher C

United States

2017-11-01T13:22:13Z

2017-11-01T13:22:13Z

2017-10-11

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010-2014, including 68 with typical SCID and 32 with leaky SCID, Omenn Syndrome or Reticular Dysgenesis. Most (59%) were diagnosed by newborn screening or family history. The 2-year overall survival (OS) was 90%but was 95% for those infection-free at HCT vs. 81% for those with active infection (p=0.009). Other factors, including the diagnosis of typical vs. leaky SCID/Omenn Syndrome, diagnosis via family history or newborn screening (FH/NBS), use of preparative chemotherapy, or the type of donor utilized did not impact survival. While 1-year post-HCT median CD4 counts and freedom from IVIG were improved after use of preparative chemotherapy, other immunologic reconstitution parameters were not affected and the potential for late sequelae in extremely young infants requires further evaluation. Following a T-cell-replete graft, landmark analysis at Day +100 post-HCT revealed that CD3 <300 cells/uL, CD8 <50 cells/uL, CD45RA <10%, or a restricted Vβ T cell receptor repertoire (<13 of 24 families) was associated with need for second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although NBS has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial is registered at www.clinicaltrials.gov as NCT01186913.

https://www.ncbi.nlm.nih.gov/pubmed/29021228

blood-2017-05-781849

1528-0020

https://hdl.handle.net/10161/15691

eng

American Society of Hematology

Blood

10.1182/blood-2017-05-781849

Immune Reconstitution and Survival of 100 SCID Patients Post Hematopoietic Cell Transplant: A PIDTC Natural History Study.

Journal article

Parikh, Suhag|0000-0002-6066-9852

Buckley, Rebecca H|0000-0002-6914-346X

https://www.ncbi.nlm.nih.gov/pubmed/29021228

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Immunology

Institutes and Centers

Pediatrics

Pediatrics, Allergy and Immunology

School of Medicine

Published online