SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery

Elie Haddad, Brent R. Logan, Linda M. Griffith, Rebecca H. Buckley, Roberta E. Parrott, Susan E. Prockop, Trudy N. Small, Jessica Chaisson, Christopher C. Dvorak, Megan Murnane, Neena Kapoor, Hisham Abdel-Azim, Imelda C. Hanson, Caridad Martinez, Jack J. H. Bleesing, Sharat Chandra, Angela R. Smith, Matthew E. Cavanaugh, Soma Jyonouchi, Kathleen E. Sullivan, Lauri Burroughs, Suzanne Skoda-Smith, Ann E. Haight, Audrey G. Tumlin, Troy C. Quigg, Candace Taylor, Blachy J. Dávila Saldaña, Michael D. Keller, Christine M. Seroogy, Kenneth B. Desantes, Aleksandra Petrovic, Jennifer W. Leiding, David C. Shyr, Hélène Decaluwe, Pierre Teira, Alfred P. Gillio, Alan P. Knutsen, Theodore B. Moore, Morris Kletzel, John A. Craddock, Victor Aquino, Jeffrey H. Davis, Lolie C. Yu, Geoffrey D. E. Cuvelier, Jeffrey J. Bednarski, Frederick D. Goldman, Elizabeth M. Kang, Evan Shereck, Matthew H. Porteus, James A. Connelly, Thomas A. Fleisher, Harry L. Malech, William T. Shearer, Paul Szabolcs, Monica S. Thakar, Mark T. Vander Lugt, Jennifer Heimall, Ziyan Yin, Michael A. Pulsipher, Sung-Yun Pai, Donald B. Kohn, Jennifer M. Puck, Morton J. Cowan, Richard J. O'Reilly, Luigi D. Notarangelo

The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 662 patients with Severe Combined Immunodeficiency (SCID) who received an Hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched sibling donors (MSD). Among recipients of non-MSD HCT, multivariate analysis showed that SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG or JAK3 defects, and was significantly better compared to patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced intensity or myeloablative conditioning had a lower incidence of treatment failure and better T and B cell reconstitution, but higher risk of graft versus host disease compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were each associated with improved survival. Typical SCID, leaky SCID and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.