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. 2023 Jun 24;11(7):1809.
doi: 10.3390/biomedicines11071809.

Outcome of BCG Vaccination in ADA-SCID Patients: A 12-Patient Series

Daniele Canarutto  1   2   3 , Chiara Oltolini  4 , Federica Barzaghi  2   3 , Valeria Calbi  2   3 , Maddalena Migliavacca  2   3 , Francesca Tucci  2   3 , Vera Gallo  2   3 , Giulia Consiglieri  2   3 , Francesca Ferrua  2   3 , Salvatore Recupero  2   3 , Maria Celia Cervi  5 , Hamoud Al-Mousa  6 , Anna Pituch-Noworolska  7 , Chiara Tassan Din  4 , Paolo Scarpellini  4 , Paolo Silvani  8 , Claudia Fossati  2 , Miriam Casiraghi  2 , Daniela Maria Cirillo  9 , Antonella Castagna  1   4 , Maria Ester Bernardo  1   2   3 , Alessandro Aiuti  1   2   3 , Maria Pia Cicalese  1   2   3
Affiliations

Outcome of BCG Vaccination in ADA-SCID Patients: A 12-Patient Series

Daniele Canarutto et al. Biomedicines. .

Abstract

Vaccination with Bacillus Calmette-Guérin (BCG) can be harmful to patients with combined primary immunodeficiencies. We report the outcome of BCG vaccination in a series of twelve patients affected by adenosine deaminase deficiency (ADA-SCID). BCG vaccination resulted in a very high incidence of complications due to uncontrolled replication of the mycobacterium. All patients who developed BCG-related disease were treated successfully and remained free from recurrence of disease. We recommend the prompt initiation of enzyme replacement therapy and secondary prophylaxis to reduce the risk of BCG-related complications in ADA-SCID patients.

Keywords: enzyme replacement therapy; gene therapy; isoniazid; newborn screening; rifampin; tuberculosis.

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Conflict of interest statement

The San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) is a joint venture between the Telethon Foundation and Ospedale San Raffaele (OSR). Gene therapy for ADA-SCID was developed at SR-TIGET and licensed to GlaxoSmithKline (GSK) in 2010. The treatments under the Named Patient Program and Hospital Exemption were provided free of charge by GSK. Strimvelis’s marketing authorization in Europe was approved in 2016 (under GSK holding), and the product is currently licensed in Iceland, Norway, Liechtenstein, and the UK. Orchard Therapeutics (Netherlands) B.V. is the marketing authorization holder in the EU and Orchard Therapeutics (Europe) Limited is the marketing authorization holder in the UK. A. Aiuti was the PI of the pilot and the pivotal SR-TIGET clinical trial of gene therapy for ADA-SCID. M.P. Cicalese is the PI of the Strimvelis Registry, RIS, and RMMs studies. All the authors declare no other relevant competing interests. D.C. conducted this study as a partial fulfillment of his Ph.D. in Molecular Medicine, International Ph.D. School, Vita-Salute San Raffaele University (Milan, Italy).

Figures

Figure 1
Figure 1
Distant BCG-related disease with visible lesions at the neck, left shoulder, and left axilla (white arrows) in patient #2.
Figure 2
Figure 2
Incidence of BCG-related disease in patients receiving secondary TB prophylaxis or not (n = 8 in no prophylaxis group and n = 4 in secondary prophylaxis group).
See this image and copyright information in PMC

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