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

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 O'Reilly, Michael Boyer, Sung-Yun Pai, Frederick Goldman, Lauri Burroughs, Sharat Chandra, Morris Kletzel, Monica Thakar, James Connelly, Geoff Cuvelier, Blachy Davila, Evan Shereck, Alan Knutsen, Kathleen E. Sullivan, Kenneth DeSantes, Alfred Gillio, Elie Haddad, Aleksandra Petrovic, Troy Quigg, Angela R. Smith, Elizabeth Stenger, Ziyan Yin, William T. Shearer, Thomas Fleisher, Rebecca H. Buckley and Christopher C. Dvorak

Key points

  • Active Infection pre-transplant adversely impacts survival (81% in those with active infection vs. 95% in those who were infection-free, p=0.009).

  • Preparative chemotherapy improved 1-year post-HCT median CD4 counts (p=0.02) and freedom from IVIG (p<0.001).

Abstract

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.

  • Submitted May 2, 2017.
  • Accepted September 20, 2017.