Immune reconstitution and survival of 100 SCID patients post–hematopoietic cell transplant: a PIDTC natural history study

Authors: Jennifer Heimall, Brent R. Logan, Morton J. Cowan, Luigi D. Notarangelo, Linda M. Griffith, Jennifer M. Puck, Donald B. Kohn, Michael A. Pulsipher, Suhag Parikh, Caridad Martinez, Neena Kapoor, Richard J. O’Reilly, Michael Boyer, Sung‐Yun Pai, Frederick D. Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica S. Thakar, James A. Connelly, Geoff D.E. Cuvelier, Blachy J. Dávila Saldaña, Evan Shereck, Alan P. Knutsen, Kathleen E. Sullivan, Kenneth B. DeSantes, Alfred P. Gillio, Élie Haddad, Aleksandra Petrović, Troy C. Quigg, Angela R. Smith, Elizabeth Stenger, Ziyan Yin, William T. Shearer, Thomas A. Fleisher, Rebecca H. Buckley, Christopher C. Dvorak - Blood 2017 cited by 266

= .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed that CD3 < 300 cells/μL, CD8 < 50 cells/μL, CD45RA < 10%, or a restricted Vβ T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening 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 was registered at www.clinicaltrials.gov as #NCT01186913.