SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Haddad Elie, Logan Brent R, Griffith Linda M, Buckley Rebecca H, Parrott Roberta E, Prockop Susan E, Small Trudy N, Chaisson Jessica, Dvorak Christopher C, Murnane Megan, Kapoor Neena, Abdel-Azim Hisham, Hanson Imelda C, Martinez Caridad, Bleesing Jack J H, Chandra Sharat, Smith Angela R, Cavanaugh Matthew E, Jyonouchi Soma, Sullivan Kathleen E, Burroughs Lauri, Skoda-Smith Suzanne, Haight Ann E, Tumlin Audrey G, Quigg Troy C, Taylor Candace, Dávila Saldaña Blachy J, Keller Michael D, Seroogy Christine M, Desantes Kenneth B, Petrovic Aleksandra, Leiding Jennifer W, Shyr David C, Decaluwe Hélène, Teira Pierre, Gillio Alfred P, Knutsen Alan P, Moore Theodore B, Kletzel Morris, Craddock John A, Aquino Victor, Davis Jeffrey H, Yu Lolie C, Cuvelier Geoffrey D E, Bednarski Jeffrey J, Goldman Frederick D, Kang Elizabeth M, Shereck Evan, Porteus Matthew H, Connelly James A, Fleisher Thomas A, Malech Harry L, Shearer William T, Szabolcs Paul, Thakar Monica S, Vander Lugt Mark T, Heimall Jennifer, Yin Ziyan, Pulsipher Michael A, Pai Sung-Yun, Kohn Donald B, Puck Jennifer M, Cowan Morton J, O'Reilly Richard J, Notarangelo Luigi D
Аннотация
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.