Bacillus Calmette-Guerin (BCG) Vaccine-associated Complications in Immunodeficient Patients Following Stem Cell Transplantation.
BCG Vaccine
/ adverse effects
Biomarkers
Child, Preschool
Diagnosis, Differential
Disease Susceptibility
Female
Graft vs Host Disease
/ diagnosis
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immunocompromised Host
Infant
Infant, Newborn
Male
Patient Outcome Assessment
Primary Immunodeficiency Diseases
/ complications
Retrospective Studies
Vaccination
/ adverse effects
BCG vaccination
hematopoietic stem cell transplantation
immune reconstitution inflammatory syndrome
primary immune deficiency
severe combined immunodeficiency
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
25
06
2020
accepted:
07
10
2020
pubmed:
29
10
2020
medline:
15
1
2022
entrez:
28
10
2020
Statut:
ppublish
Résumé
Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine with the potential of causing severe iatrogenic complications in patients with primary immunodeficiency diseases (PID) before and after hematopoietic stem cell transplantation (HSCT). We aim to investigate risk factors of post-HSCT BCG-related complications in PID patients. A retrospective analysis of pediatric PID patients who had received the BCG vaccine and underwent HSCT at Hadassah-Hebrew University Medical Center, between 2007 and 2019. We found 15/36 (41.67%) patients who developed post-HSCT BCG-related complications. The most significant risk factor for developing BCG-related complications was T cell deficiency (47.6% of the non-complicated vs 83.3% of the BCGitis and 100% of the BCGosis groups had T cell lymphopenia, p = 0.013). None of the chronic granulomatous patients developed BCG-related manifestation post-transplant. Among T cell-deficient patients, lower NK (127 vs 698 cells/μl, p = 0.04) cell counts and NK-SCID were risk factors for ongoing post-HSCT BCGosis, as was pretransplant disseminated BCGosis (33.3% of patients with BCGosis vs none of the non-BCGosis patients, p = 0.04). Immune reconstitution inflammatory syndrome (IRIS) was observed in 3/5 patients with Omenn syndrome. Prophylactic antimycobacterial treatment was not proven effective. BCG vaccination can cause significant morbidity and mortality in the post-transplant T cell-deficient patient, especially in the presence of pre-transplant disease. Taking a detailed medical history prior to administering, the BCG vaccine is crucial for prevention of this complication.
Identifiants
pubmed: 33111199
doi: 10.1007/s10875-020-00892-6
pii: 10.1007/s10875-020-00892-6
pmc: PMC7591244
doi:
Substances chimiques
BCG Vaccine
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-162Références
WHO. Global tuberculosis report 2019. WHO; 2020
Liu J, Tran V, Leung AS, Alexander DC, Zhu B. BCG vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy. Hum Vaccin. 2009;5:70–8.
pubmed: 19164935
Marciano BE, Huang CY, Joshi G, Rezaei N, Carvalho BC, Allwood Z, et al. BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies. J Allergy Clin Immunol. 2014;133(4):1134–41 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24679470 .
pubmed: 24679470
pmcid: 4015464
Hesseling AC, Rabie H, Marais BJ, Manders M, Lips M, Schaaf HS, et al. Bacille Calmette-Guerin vaccine–induced disease in HIV-infected and HIV-uninfected children. Clin Infect Dis. 2006;42(4):548–58.
pubmed: 16421800
Ying W, Sun J, Liu D, Hui X, Yu Y, Wang J, et al. Clinical characteristics and immunogenetics of BCGosis/BCGitis in Chinese children: a 6 year follow-up study. PLoS One. 2014;9(4):e94485 [Internet]. [cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24722620 .
pubmed: 24722620
pmcid: 3983162
Fekrvand S, Yazdani R, Olbrich P, Gennery A, Rosenzweig SD, Condino-Neto A, et al. Primary Immunodeficiency Diseases and Bacillus Calmette-Guérin (BCG)-vaccine–derived complications: a systematic review. J Allergy Clin Immunol Pract. 2020;8(4):1371–86 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32006723 .
pubmed: 32006723
Norouzi S, Aghamohammadi A, Mamishi S, Rosenzweig SD, Rezaei N. Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases. J Infect. 2012;64:543–54.
pubmed: 22430715
pmcid: 4792288
Al-Hammadi S, Alsuwaidi AR, Alshamsi ET, Ghatasheh GA, Souid AK. Disseminated Bacillus Calmette-Guérin (BCG) infections in infants with immunodeficiency. BMC Res Notes. 2017;10(1):177. https://doi.org/10.1186/s13104-017-2499-7 .
Sadeghi-Shanbestari M, Ansarin K, Maljaei SH, Rafeey M, Pezeshki Z, Kousha A, et al. Immunologic aspects of patients with disseminated bacille Calmette-Guerin disease in north-west of Iran. Ital J Pediatr. 2009;35(42):42 [Internet]. [cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20030825 .
pubmed: 20030825
pmcid: 2806263
Lee W-I, Huang J-L, Yeh K-W, Jaing T-H, Lin T-Y, Huang Y-C, et al. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs). J Formos Med Assoc. 2011;110(12):750–8 [Internet]. [cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22248828 .
pubmed: 22248828
Pöyhönen L, Bustamante J, Casanova JL, Jouanguy E, Zhang Q. Life-threatening infections due to live-attenuated vaccines: early manifestations of inborn errors of immunity [Internet]. J Clin Immunol. 2019;39:376–90 Springer New York LLC. [cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31123910 .
pubmed: 31123910
pmcid: 7192346
De Beaucoudrey L, Samarina A, Bustamante J, Cobat A, Boisson-Dupuis S, Feinberg J, et al. Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries. Medicine. 2010;89:381–402.
pubmed: 21057261
pmcid: 3129625
Conti F, Lugo-Reyes SO, Blancas Galicia L, He J, Aksu G, Borges de Oliveira E, et al. Mycobacterial disease in patients with chronic granulomatous disease: a retrospective analysis of 71 cases. J Allergy Clin Immunol. 2016;138(1):241–248.e3 [Internet]. [cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26936803 .
pubmed: 26936803
Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International Union of Immunological Societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38(1):96–128.
pubmed: 29226302
Roifman CM, Somech R, Kavadas F, Pires L, Nahum A, Dalal I, et al. Defining combined immunodeficiency. J Allergy Clin Immunol. 2012;130(1):177–83.
pubmed: 22664165
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from hl-a-matched sibling donors1. Transplantation. 1974;18(4):295–304.
pubmed: 4153799
Stepensky P, Keller B, Shamriz O, NaserEddin A, Rumman N, Weintraub M, et al. Deep intronic mis-splicing mutation in JAK3 gene underlies T-B+NK- severe combined immunodeficiency phenotype. Clin Immunol. 2016;163:91–5.
pubmed: 26769277
Gantzer A, Neven B, Picard C, Brousse N, Lortholary O, Fischer A, et al. Severe cutaneous bacillus Calmette-Guérin infection in immunocompromised children: the relevance of skin biopsy. J Cutan Pathol. 2013;40(1):30–7 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23157280 .
pubmed: 23157280
Erbey F, Dur AH, Atay D, Akçay A, Tecimer T, Öztürk G. Successful treatment of BCG-related immune reconstitution inflammatory syndrome following ex vivo T-cell-depleted haploidentical hematopoietic stem cell transplantation: a case report. Pediatr Transplant. 2019;23(5):e13464 [Internet]. [cited 2020 May 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31081274 .
pubmed: 31081274
Abu-Arja RF, Gonzalez BE, Jacobs MR, Cabral L, Egler R, Auletta J, et al. Primary immunodeficiency diseases and Bacillus Calmette-Guérin (BCG)-vaccine–derived complications: a systematic review. J Allergy Clin Immunol Pract. 2020;8(4):1371–86 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32006723 .
Aytekin C, Yuksek M, Dogu F, Yagmurlu A, Yildiran A, Fitoz S, Kologlu M, Babacan E, Hershfield MS, Ikinciogullari A. An unconditioned bone marrow transplantation in a child with purine nucleoside phosphorylase deficiency and its unique complication. Pediatr Transplant. 2008;12(4):479–82. https://doi.org/10.1111/j.1399-3046.2007.00890.x .
Amayiri N, Al-Zaben A, Ghatasheh L, Frangoul H, Hussein AA. Hematopoietic stem cell transplantation for children with primary immunodeficiency diseases: single center experience in Jordan. Pediatr Transplant. 2013;17(4):394–402 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23692601 .
pubmed: 23692601
Bacalhau S, Freitas C, Valente R, Barata D, Neves C, Schäfer K, et al. Successful handling of disseminated BCG disease in a child with severe combined immunodeficiency. Case Rep Med. 2011;2011:527569 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22110512 .
pubmed: 22110512
pmcid: 3202142
Bernatowska EA, Wolska-Kusnierz B, Pac M, Kurenko-Deptuch M, Zwolska Z, Casanova JL, et al. Disseminated bacillus Calmette-Guérin infection and immunodeficiency [14]. Emerg Infect Dis. Centers for Disease Control and Prevention (CDC). 2007;13:799–801.
pubmed: 18044052
pmcid: 2738440
Heyderman RS, Morgan G, Levinsky RJ, Strobel S. Successful bone marrow transplantation and treatment of BCG infection in two patients with severe combined immunodeficiency. Eur J Pediatr. 1991;150(7):477–80.
pubmed: 1915499
Ikincioğullari A, Doğu F, Ciftci E, Unal E, Ertem M, Reisli I, et al. An intensive approach to the treatment of disseminated BCG infection in a SCID patient. Bone Marrow Transplant. 2002;30(1):45–7 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12105777 .
pubmed: 12105777
Laberko A, Yukhacheva D, Rodina Y, Abramov D, Konovalov D, Radygina S, et al. BCG-related inflammatory syndromes in severe combined immunodeficiency after TCRαβ+/CD19+ depleted HSCT. J Clin Immunol. 2020;40(4):625–36 [Internet]. [cited 2020 Aug 16]. Available from: https://pubmed.ncbi.nlm.nih.gov/32377975/ .
pubmed: 32377975
Jaing T-H, Lee W-I, Lin T-Y, Huang J-L, Chen S-H, Chow R. Successful unrelated mismatched cord blood transplantation in an infant with severe combined immunodeficiency and Mycobacterium bovis bacillus Calmette-Guèrin disease. Pediatr Transplant. 2006;10(4):501–4 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16712611 .
pubmed: 16712611
McKenzie RH, Roux P. Disseminated BCG infection following bone marrow transplantation for X-linked severe combined immunodeficiency. Pediatr Dermatol. 2000;17(3):208–12 [Internet]. [cited 2020 may 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10886754 .
pubmed: 10886754
Skinner R, Appleton AL, Sprott MS, Barer MR, Magee JG, Darbyshire PJ, et al. Disseminated BCG infection in severe combined immunodeficiency presenting with severe anaemia and associated with gross hypersplenism after bone marrow transplantation. Bone Marrow Transplant. 1996;17(5):877–80 [Internet]. [cited 2020 may 12]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8733714 .
pubmed: 8733714
Fisch P, Millner M, Müller SM, Wahn U, Friedrich W, Renz H. Expansion of γδt cells in an infant with severe combined immunodeficiency syndrome after disseminated BCG infection and bone marrow transplantation. J Allergy Clin Immunol. 1999;103(6):1218–9.
pubmed: 10359912
Lee PPW, Chan KW, Chen TX, Jiang LP, Wang XC, Zeng HS, et al. Molecular diagnosis of severe combined immunodeficiency—identification of IL2RG, JAK3, IL7R, DCLRE1C, RAG1, and RAG2 mutations in a cohort of Chinese and Southeast Asian children. J Clin Immunol. 2011;31(2):281–96 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21184155 .
pubmed: 21184155
Naselli A, Losurdo G, Giardino S, Morreale G, Savioli C, Castagnola E. Successful management of cutaneous BCG dissemination in a child affected by SCID and receiving allogeneic hematopoietic stem cell transplant. Bone Marrow Transplant. 2015;50(12):1572–3 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26121110 .
pubmed: 26121110
Wahadneh A, Bin-Dahman H, Habahbeh Z, Abu-Shukear M, Ajarmeh M, Zyood R, Khaled A. Successful second bone marrow transplantation in Omenn's syndrome after bone marrow aplasia: a case report. Pediatr Transplant. 2012;16(2):E43–8. https://doi.org/10.1111/j.1399-3046.2010.01413.x .
Yildiran A, Fişgin T, Güner SN, Kiliç M, Sancak R, Özyürek E, et al. Hemophagocytic bone marrow aplasia with plasma cells in a RAG2-deficient SCID case after a nonconditioned transplantation from a fully matched sibling. J Pediatr Hematol Oncol. 2013;35(8):e335–7 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23389499 .
pubmed: 23389499
Deffert C, Schäppi MG, Pache JC, Cachat J, Vesin D, Bisig R, Ma Mulone X, Kelkka T, Holmdahl R, Garcia I, Olleros ML, Krause KH. Bacillus calmette-guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation. PLoS Pathog. 2014;10(9):e1004325. https://doi.org/10.1371/journal.ppat.1004325 .
Lin CJ, Wang SC, Ku CL, Kao JK, Chen M, Liu CS. Successful unrelated cord blood stem cell transplantation in an X-linked chronic granulomatous disease patient with disseminated BCG-induced infection. Pediatr Neonatol. 2015;56(5):346–50.
pubmed: 23680261
Moliva JI, Turner J, Torrelles JB. Immune Responses to Bacillus Calmette-Guérin vaccination: why do they fail to protect against Mycobacterium tuberculosis? Front Immunol. 2017;8(APR):407. [Internet]. [cited 2020 APR 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28424703 .
Mazzucchelli JTL, Bonfim C, Castro GG, Condino-Neto AA, Costa NMX, Cunha L, et al. Severe combined immunodeficiency in Brazil: management, prognosis, and BCG-associated complications. J Investig Allergol Clin Immunol. 2014;24(3):184–91.
pubmed: 25011356
French MA. Immune reconstitution inflammatory syndrome: a reappraisal. Clin Infect Dis. 2009;48(1):101–7 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19025493 .
pubmed: 19025493
Bozzano F, Marras F, De Maria A. Immunology of tuberculosis [Internet]. Mediterr J Hematol Infect Dis. 2014;6:e2014027 Universita Cattolica del Sacro Cuore; [cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24804000 .
pubmed: 24804000
pmcid: 4010607
Millman AC, Salman M, Dayaram YK, Connell ND, Venketaraman V. Natural killer cells, glutathione, cytokines, and innate immunity against Mycobacterium tuberculosis. J Interf Cytokine Res. 2008 Mar 1;28(3):153–65.
Cotton MF, Rabie H, Nemes E, Mujuru H, Bobat R, Njau B, Violari A, Mave V, Mitchell C, Oleske J, Zimmer B, Varghese G, Pahwa S; P1073 team. A prospective study of the immune reconstitution inflammatory syndrome (IRIS) in HIV-infected children from high prevalence countries. PLoS One. 2019;14(7):e0211155. https://doi.org/10.1371/journal.pone.0211155 .
Sun HY, Singh N. Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients. Curr Opin Infect Dis. 2009;22:394–402.
pubmed: 19483618
Scharschmidt TC, Amerson EH, Rosenberg OS, Jacobs RA, McCalmont TH, Shinkai K. Immune reconstitution reactions in human immunodeficiency virus-negative patients: report of a case and review of the literature. JAMA Dermatol. 2013;149(1):74–8.
pubmed: 23324760
pmcid: 3773570
Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol. 2008;122(6):1082–6.
pubmed: 18992930
Sun HY, Singh N. Opportunistic infection-associated immune reconstitution syndrome in transplant recipients. Clin Infect Dis. 2011;53(2):168–76 [Internet]. [cited 2020 May 8]. Available from: https://www-ncbi-nlm-nih-gov.clalit-ez.medlcp.tau.ac.il/pubmed/?term=Opportunistic+Infection-Associated+Immune+Reconstitution+Syndrome+in+Transplant+Recipients .
pubmed: 21690625
Searle E, Patel H, Vilar FJ, Gharib M, Turner AJ, Batra G, et al. Inflammatory BCG adenitis associated with immune reconstitution following allogeneic haematopoietic stem cell transplant in infancy. Pediatr Blood Cancer. 2010;54(1):166–9 [Internet]. [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19606456 .
pubmed: 19606456
Yu R, Satoh T, Wakabayashi T, Ueda N, Yokozeki H. Disseminated BCG infection in severe combined immunodeficiency [Internet]. Acta Derm Venereol. 2012;92:158–9 [cited 2020 Apr 16]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21879238 .
pubmed: 21879238
World Health Organization. BCG vaccine: WHO position paper, February 2018, Recommendations [Internet]. Vaccine. 2018;36:3408–10 Elsevier Ltd; [cited 2020 May 6]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29609965 .
pubmed: 29609965
Koppel A, Leonardo-Guerrero J, Rives S, Paniagua-Torres N, Sparrow C, Beck-Sagué CM. Immune reconstitution inflammatory syndrome due to Mycobacterium bovis Bacillus Calmette-Guerin in infants receiving highly active antiretroviral therapy: a call for universal perinatal rapid HIV testing prior to administration of BCG immunization of neonates. J Trop Pediatr. 2010;56(4):280–3 [Internet]. [cited 2020 May 14]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19952057 .
pubmed: 19952057
de Jesus Nunes-Santos C, Rosenzweig SD. Bacille Calmette-Guerin complications in newly described primary immunodeficiency diseases: 2010-2017 [Internet]. Front Immunol. 2018;9:1423 Frontiers Media S.A.[cited 2020 Apr 20]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29988375 .
Bacille Calmette-Guérin (BCG) vaccination and COVID-19 Scientific brief 12 April 2020 Summary. In: clinicaltrials.gov. 2020 [cited 2020; Available from: http://www.clinicaltrials.gov/ct2/show/NCT04327206 .
Hamiel U, Kozer E, Youngster I. SARS-CoV-2 Rates in BCG-Vaccinated and Unvaccinated Young Adults. JAMA. 2020;323(22):2340–2341. https://doi.org/10.1001/jama.2020.8189 .