| Literature DB >> 30154114 |
Elie Haddad1, Brent R Logan2, Linda M Griffith3, Rebecca H Buckley4, Roberta E Parrott4, Susan E Prockop5, Trudy N Small5, Jessica Chaisson5, Christopher C Dvorak6, Megan Murnane6, Neena Kapoor7, Hisham Abdel-Azim7, Imelda C Hanson8, Caridad Martinez9, Jack J H Bleesing10, Sharat Chandra10, Angela R Smith11, Matthew E Cavanaugh12, Soma Jyonouchi13, Kathleen E Sullivan13, Lauri Burroughs14,15, Suzanne Skoda-Smith15, Ann E Haight16, Audrey G Tumlin16, Troy C Quigg17, Candace Taylor17, Blachy J Dávila Saldaña18, Michael D Keller18, Christine M Seroogy19, Kenneth B Desantes19, Aleksandra Petrovic20, Jennifer W Leiding20,21, David C Shyr22, Hélène Decaluwe1, Pierre Teira1, Alfred P Gillio23, Alan P Knutsen24, Theodore B Moore25, Morris Kletzel26, John A Craddock27, Victor Aquino28, Jeffrey H Davis29, Lolie C Yu30, Geoffrey D E Cuvelier31, Jeffrey J Bednarski32, Frederick D Goldman33, Elizabeth M Kang34, Evan Shereck35, Matthew H Porteus36, James A Connelly37, Thomas A Fleisher38, Harry L Malech34, William T Shearer8, Paul Szabolcs39, Monica S Thakar40, Mark T Vander Lugt41, Jennifer Heimall13, Ziyan Yin2, Michael A Pulsipher7, Sung-Yun Pai12, Donald B Kohn25, Jennifer M Puck6, Morton J Cowan6, Richard J O'Reilly5, Luigi D Notarangelo42.
Abstract
The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a 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 (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the 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 with 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 a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 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.Entities:
Mesh：
Year: 2018 PMID： 30154114 PMCID： PMC6202916 DOI： 10.1182/blood-2018-03-840702
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113