Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Thakar Monica S, Logan Brent R, Puck Jennifer M, Dunn Elizabeth A, Buckley Rebecca H, Cowan Morton J, O'Reilly Richard J, Kapoor Neena, Satter Lisa Forbes, Pai Sung-Yun, Heimall Jennifer, Chandra Sharat, Ebens Christen L, Chellapandian Deepak, Williams Olatundun, Burroughs Lauri M, Saldana Blachy Davila, Rayes Ahmad, Madden Lisa M, Chandrakasan Shanmuganathan, Bednarski Jeffrey J, DeSantes Kenneth B, Cuvelier Geoffrey D E, Teira Pierre, Gillio Alfred P, Eissa Hesham, Knutsen Alan P, Goldman Frederick D, Aquino Victor M, Shereck Evan B, Moore Theodore B, Caywood Emi H, Lugt Mark T Vander, Rozmus Jacob, Broglie Larisa, Yu Lolie C, Shah Ami J, Andolina Jeffrey R, Liu Xuerong, Parrott Roberta E, Dara Jasmeen, Prockop Susan, Martinez Caridad A, Kapadia Malika, Jyonouchi Soma C, Sullivan Kathleen E, Bleesing Jack J, Chaudhury Sonali, Petrovic Aleksandra, Keller Michael D, Quigg Troy C, Parikh Suhag, Shenoy Shalini, Seroogy Christine, Rubin Tamar, Decaluwe Hélène, Routes John M, Torgerson Troy R, Leiding Jennifer W, Pulsipher Michael A, Kohn Donald B, Griffith Linda M, Haddad Elie, Dvorak Christopher C, Notarangelo Luigi D
Аннотация
METHODS: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18. Categorical variables were compared by χ2 test and continuous outcomes by the Kruskal-Wallis test. Overall survival was estimated by the Kaplan-Meier method. A multivariable analysis using Cox proportional hazards regression models examined risk factors for HCT outcomes, including the variables of time interval of HCT, infection status and age at HCT, trigger for diagnosis, SCID type and genotype, race and ethnicity of the patient, non-HLA-matched sibling donor type, graft type, GVHD prophylaxis, and conditioning intensity.
FINDINGS: For 902 children with confirmed SCID, 5-year overall survival remained unchanged at 72%-73% for 28 years until 2010-18, when it increased to 87% (95% CI 82·1-90·6; n=268; p=0·0005). For children identified as having SCID by newborn screening since 2010, 5-year overall survival was 92·5% (95% CI 85·8-96·1), better than that of children identified by clinical illness or family history in the same interval (79·9% [69·5-87·0] and 85·4% [71·8-92·8], respectively [p=0·043]). Multivariable analysis demonstrated that the factors of active infection (hazard ratio [HR] 2·41, 95% CI 1·56-3·72; p<0·0001), age 3·5 months or older at HCT (2·12, 1·38-3·24; p=0·001), Black or African-American race (2·33, 1·56-3·46; p<0·0001), and certain SCID genotypes to be associated with lower overall survival during all time intervals. Moreover, after adjusting for several factors in this multivariable analysis, HCT after 2010 no longer conveyed a survival advantage over earlier time intervals studied (HR 0·73, 95% CI 0·43-1·26; p=0·097). This indicated that younger age and freedom from infections at HCT, both directly driven by newborn screening, were the main drivers for recent improvement in overall survival.
INTERPRETATION: Population-based newborn screening has facilitated the identification of infants with SCID early in life, in turn leading to prompt HCT while avoiding infections. Public health programmes worldwide can benefit from this definitive demonstration of the value of newborn screening for SCID.
FUNDING: National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research, and National Center for Advancing Translational Sciences.