To identify the types and timing of infections in infants with severe combined immunodeficiency (SCID), who were either diagnosed by newborn screen (NBS) or family history (FH), before hematopoietic stem cell transplant (HSCT). Additionally, in the study, the researchers assessed infection prevention management practices used by Primary Immune Deficiency Treatment Consortium (PIDTC) centers in SCID infants before HSCT.In this study, we included 59 infants diagnosed with SCID via NBS or FH who underwent HSCT (PIDTC protocol 6901) among 25 different PIDTC centers between 2010–2014.This study had 2 parts. Part 1 was a retrospective chart review in which researchers evaluated age at SCID diagnosis, method of diagnosis (NBS versus FH), age at infection onset, type and frequency of infection(s), time to HSCT, and outcomes. Part 2 was a 29-question survey administered to 42 PIDTC centers inquiring about their pre-HSCT management practices for SCID infants. With the survey, the researchers assessed infection prevention management practices including location (inpatient versus outpatient), antimicrobial prophylaxis, immunoglobulin therapies, and practices for monitoring and preventing viral infections.Part 1 (infection and survival outcomes) results were as follows: Among the 59 infants diagnosed with SCID, 64% were diagnosed via NBS, and 36% were diagnosed via FH. Infants with FH were diagnosed significantly earlier than those diagnosed by NBS (median: 6 days versus 25 days, respectively; P < .001). Patients diagnosed via NBS were more likely to experience at least 1 pre-HSCT infection, compared with those diagnosed by FH (55% vs 19%; P = .012) and had higher infection density (0.3 per month versus 0.1 per month; P = .029). The rate of active infection at the time of HSCT was higher in patients diagnosed by NBS (39% vs 5%; P = .005). The location of pre-HSCT management (outpatient versus inpatient) did not impact infection rates. The most common infections reported in both groups were cytomegalovirus, Epstein-Barr virus, and respiratory viruses. The median time to HSCT was significantly longer in those diagnosed by NBS, compared with that of those diagnosed by FH (96.5 days versus 49 days; P < .001). Two-year survival post-HSCT was comparable (89%) in both groups. Part 2 (survey) results were as follows: 50 physicians from 42 PIDTC centers completed the survey with 100% response rate. Initiation of SCID management was started at a median age of 21 days. There were variable recommendations on location of pre-HSCT management, although 31% routinely planned for inpatient care and 17% routinely planned for outpatient care. Inpatient hygiene measures were variable, but most (70%) recommended reverse isolation with (50%) or without (20%) positive pressure ventilation. Most centers (79%) restricted nonstaff caregivers to 2 individuals. Antimicrobial prophylaxis was recommended against Pneumocystis jiroveci universally (most commonly, trimethoprim-sulfamethoxazole: 91%), although the age at initiation varied. Fungal prophylaxis was routinely started by 79%, although the timing and agent varied. Most providers (98%) used immunoglobulin, although routes varied. A minority of centers (45%) routinely recommended viral prophylaxis with acyclovir. Routine viral screening was performed for cytomegalovirus at 93% of centers, whereas monitoring for other viruses (Epstein-Barr virus and adenovirus) was not consistent.Infants diagnosed with SCID via FH were diagnosed sooner, were less likely to develop infection pre-HSCT, and had a shorter time to HSCT, when compared with those diagnosed by NBS. Despite this, 2-year survival post-HSCT was the same. Pre-HSCT medical management was variable among PIDTC centers, specifically the location of pre-HSCT management outpatient versus that of inpatient.T-cell receptor excision circle analysis is an easy and efficient way to screen for SCID and now part of the NBS in all 50 states. Because of this, we are now able to diagnose and intervene early for SCID infants, greatly improving these vulnerable patients’ clinical outcomes. Despite this, when comparing infants diagnosed with SCID by NBS with those diagnosed by FH, NBS falls short. In this study, the authors found that infants diagnosed with SCID by NBS had a longer time to diagnosis and HSCT, had a higher infection density, and were more likely to be infected at time of HSCT. Although all 50 states screen for SCID on NBS, it is clear there is more work to be done to streamline evaluation and management to reduce delays to and infections before HSCT. Additionally, there is robust data supporting early HSCT to improve clinical outcomes, but even at PIDTC centers, pre-HSCT management practices for SCID infants is variable. Clinicians would benefit from more uniform SCID management guidelines in the future.
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Apr 23, 2024
Christin Deal + 20
Open Access