Background SCID is a syndrome characterized by profound T cell deficiency. BCG vaccine is contraindicated in SCID patients. Because most countries encourage BCG vaccination at birth, a high percent of SCID patients are vaccinated before their immune defect is detected. Objectives To describe the complications and risks associated with BCG vaccination in SCID patients. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcome regarding BCG in patients diagnosed with SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG vaccinated SCID patients from 28 centers in 17 countries was analyzed. Fifty-one percent of the patients developed BCG complications, 34% disseminated and 17% localized (a 33,000 and 400 fold increase, respectively, over the general population). Patients receiving early vaccination (≤ 1 month) showed an increased prevalence of complications (p=0.006) and death due to BCG complications (p<0.0001). The odds of experiencing complications among patients with T cells ≤ 250/uL at diagnosis was 2.1 times higher (95% CI, 1.4-3.4; p = 0.001) than among those with T cells > 250/uL. BCG complications were reported in 2/78 patients who received anti-mycobacterial therapy while asymptomatic and no deaths due to BCG complications occurred in this group. In contrast 46 BCG-associated deaths were reported among 160 patients treated with anti-mycobacterial therapy for a symptomatic BCG infection (p<0.0001). Conclusions BCG vaccine has a very high rate of complications in SCID patients, which increase morbidity and mortality rates. Until safer and more efficient anti-tuberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved. (Blood. 2012;120(17):3615-3624)

Severe combined immunodeficiency (SCID) carries a poor prognosis without definitive treatment by hematopoietic stem cell transplantation. The outcome for transplantation varies and is dependent on donor status and the condition of the child at the time of transplantation. Diagnosis at birth may allow for better protection of SCID babies from infection and improve transplantation outcome. In this comparative study conducted at the 2 designated SCID transplantation centers in the United Kingdom, we show that SCID babies diagnosed at birth because of a positive family history have a significantly improved outcome compared with the first presenting family member. IntroductionSevere combined immunodeficiencies (SCIDs) are a genetically heterogeneous group of inherited defects characterized by severe abnormalities of immune system development and function. 1,2 Affected infants present in the first few months of life with severe and recurrent infections; without definitive treatment, the condition is invariably fatal. The genetic defects in approximately 90% of the different forms of SCID have now been identified; and despite genetic heterogeneity, all patients are characterized by abnormalities of thymopoiesis and T-cell maturation and function.Definitive treatment is available for SCID predominantly by allogeneic hematopoietic stem cell transplantation (HSCT) 3,4 but also in specific forms of SCID (SCID-X1 and ADA-SCID) by gene therapy 5-8 and by enzyme replacement therapy for adenosine deaminase (ADA) SCID. 9 Detailed analysis of a large European SCID cohort showed that survival after HSCT was dependent on a number of factors. 3 Patients transplanted before 6 months of age had a significantly better outcome. Matched sibling donor and matched unrelated donor transplants in SCID had approximately 90% and 80% 3-year survival rates, respectively, whereas mismatched transplants predominantly from parental donors showed a 65% success rate. The outcomes in the T Ϫ B Ϫ and ADA-deficient forms of SCID were also shown to be less successful, especially after mismatched donor transplants. Also important was the presence of pneumonitis before transplantation, with patients who have had such infections having a significantly poorer outcome (P Ͻ .0001).Over the last 5 years, considerable interest has been generated by the ability to screen for SCID babies at birth. Detection of recent thymic emigrants by quantitative polymerase chain reaction of DNA extracted from neonatal dried blood spots can detect all SCID forms regardless of genetic diagnosis. 10,11 The potential advantage of SCID newborn screening would be to protect infants at the time of birth from respiratory pathogens, including Pneumocystis jiroveci, and respiratory viruses (eg, adenovirus and parainfluenzae), and to undertake a transplantation at an earlier age. Myers et al 12 showed that this strategy may be effective in 21 patients diagnosed at birth, but in this series all patients received an unconditioned procedure with the majority (19 of 21) receiving a T cell-...

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