Consensus guidelines for management of ADA-SCID released
Published Date: 13/11/18Access Full Text Article
In light of the advances in the treatment options for ADA deficiency that have occurred since the initial set of guidelines were issued almost a decade ago, the group – comprising clinicians and researchers as well as representatives of patient advocacy groups, the pharmaceutical industry and US government – set out “to review the new information and provide updated guidance.”
With regard to the treatment of immune deficiency, the guideline authors advise the initiation of enzyme replacement therapy (ERT) in all newly diagnosed patients “as an immediate stabilizing measure”, but note that for most patients, “ERT should be used as a ‘bridge’ for relatively short periods” until definitive procedures can be employed.
Based on the available evidence, they believe that allogeneic haematopoietic stem cell transplantation (HSCT) using cells from an HLA-matched sibling donor (MSD) or matched family donor (MFD), and autologous HSC-gene therapy (GT) with a gamma-retroviral or lentiviral vector are equally viable definitive options for the treatment of ADA-deficient patients.
The consideration of HSC-GT as one of the first-line treatment choices for ADA-SCID represents “a major change” from earlier guidelines and “reflects the promising results” obtained with the approach, say Eyal Grunebaum, from The Hospital for Sick Children in Toronto, Ontario, Canada, and fellow guideline authors.
They highlight, however, that the currently approved GT Strimvelis (Orchard Therapeutics [Netherlands] BV) is only indicated in the European Union for patients for whom a suitable MSD is not available and that the associated costs are thought to be more than those for HSCT.
Patients without a suitable MSD or MFD or access to HSC-GT are a “particularly challenging” population, say the consensus authors. Although ERT is often continued for extended periods in these patients, it often does not lead to sustained restoration of immunity and is expensive, leading the authors to recommend against its indefinite use.
They therefore emphasise that “the possibility of HSCT using alternative donors needs to be considered in all newly diagnosed patients”, even though the outcomes are not as good as with an MSD or MFD.
Finally, for patients who have impaired immunity even after receiving the first definitive therapy, several options are recommended, including repeating the procedure after a suitable interval. If the initial procedure was HSCT, they suggest altering the conditioning regimen or using a different graft source when it is repeated.
In the article published in The Journal of Allergy and Clinical Immunology, the authors have also included a treatment algorithm for managing the condition, but they acknowledge that “management choices depend on experience and knowledge of health care providers, the patient’s and family’s preferences, institutional policies, access and availability of treatments, national health systems and insurers decisions, new information in the rapidly developing field of ERT, HSCT and HSC-GT.”
Therefore, they stress that “the proposed algorithm should serve as a guideline, rather than a mandated structured treatment map.”
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