Approximately ∼13% of instances of severe combined immune deficiency (SCID) are due to adenosine deaminase (ADA) deficiency. Gene therapy (GT), hematopoietic cell transplantation (HCT), and enzyme replacement therapy (ERT) are examples of treatment.
For a study, researchers sought to look at 131 patients who had been engaged in the Primary Immune Deficiency Treatment Consortium SCID trials and had been diagnosed with ADA-SCID between 1982 and 2017. Clinical, immunologic, genetic, and therapeutic results at baseline were examined.
A total of 56 patients had their first definitive cellular therapy (FDCT) receiving HCT without preceding ERT (HCT), 31 received ERT before getting HCT (ERT-HCT), and 33 received GT before receiving ERT (ERT-GT). About 49.5% for HCT, 73% for ERT-HCT, and 75.3% for ERT-GT; P<.01; for 5 years of event-free survival (EFS, alive, no need for more ERT or cellular treatment). Five years following FDCT, the overall survival (OS) rates were 72.5% (HCT), 79.6% (ERT-HCT), and 100% (ERT-GT; P=.01). Patients having HCT at <3.5 months of age had a better 5-year OS (91.6% vs 68% if ≥3.5 months, P=.02). The 5-year EFS (33.1% vs 68.2%, P<.01) and OS (64.7% vs 82.3%, P=.02) were worse in patients who had an active infection at the time of HCT (independent of ERT). For matched sibling and matched family donors (MSD/MFD), 5-year EFS (90.5%) and OS (100%) performed best.
There was no difference between HCT utilizing a variety of transplant techniques and ERT-GT for patients treated after the year 2000 who had no current infection at the time of FDCT in terms of 5-year EFS or OS. When MSD/MFD HCT and GT were not accessible, it implied that alternate donor HCT may be investigated. It was especially true when newborn screening detects patients with ADA-SCID shortly after delivery and before the start of infections.