TY - JOUR
T1 - Bacillus Calmette-Guérin Retains Clinically Relevant Viability for up to 72 Hours After Reconstitution
T2 - Potential Implications for Clinical Practice in Times of Shortage
AU - Brooks, Nathan
AU - Nagaraju, Supriya
AU - Matulay, Justin
AU - Han, Xiang Yang
AU - Kamat, Ashish M.
N1 - Publisher Copyright:
Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - There have been repeated supply shortages of bacillus Calmette-Guérin (BCG), the gold-standard immunotherapy for patients with high-grade non-muscle-invasive bladder cancer (NMIBC). Organizations have issued guidance on coping with this shortage, including administering split-dose BCG such that one vial may treat up to three patients. However, logistical implementation of this strategy in a real-world setting is hampered by the recommendation to use BCG within 2 h of reconstitution. We assessed BCG viability in terms of colony-forming units (CFUs) and demonstrated that viability remained constant for at least 8 h after reconstitution (decline at 8 h of 9.1% for lot 1 [p = 0.3] and 4.8% for lot 2 [p = 0.2]). While the viability at 24 h was lower, it did not drop to a level below that of reducing the BCG dose to one-third (67% for lot 1 and 60% for lot 2) and remained close to 50% for at least 72 h. An in vitro model using co-culture of BCG and leukocytes with a BCG-sensitive cell line (RT4-V6) demonstrated no decrease in the cytotoxic potential of BCG at 72 h. In times of shortage, BCG vials may be split and administered for up to at least 8 h (or even 72 h) after reconstitution, allowing more patients to benefit from BCG while placing less strain on the logistics of clinical practice. PATIENT SUMMARY: The current supply of and increased demand for bacillus Calmette-Guérin (BCG), used in the treatment of bladder cancer, have led to repeated BCG shortages. One way to address this is to provide a reduced BCG dose to allow more patients to be treated. In this study we found that BCG viability remains clinically relevant up to 72 h after reconstitution, thus allowing for more patients to be treated from a single vial.
AB - There have been repeated supply shortages of bacillus Calmette-Guérin (BCG), the gold-standard immunotherapy for patients with high-grade non-muscle-invasive bladder cancer (NMIBC). Organizations have issued guidance on coping with this shortage, including administering split-dose BCG such that one vial may treat up to three patients. However, logistical implementation of this strategy in a real-world setting is hampered by the recommendation to use BCG within 2 h of reconstitution. We assessed BCG viability in terms of colony-forming units (CFUs) and demonstrated that viability remained constant for at least 8 h after reconstitution (decline at 8 h of 9.1% for lot 1 [p = 0.3] and 4.8% for lot 2 [p = 0.2]). While the viability at 24 h was lower, it did not drop to a level below that of reducing the BCG dose to one-third (67% for lot 1 and 60% for lot 2) and remained close to 50% for at least 72 h. An in vitro model using co-culture of BCG and leukocytes with a BCG-sensitive cell line (RT4-V6) demonstrated no decrease in the cytotoxic potential of BCG at 72 h. In times of shortage, BCG vials may be split and administered for up to at least 8 h (or even 72 h) after reconstitution, allowing more patients to benefit from BCG while placing less strain on the logistics of clinical practice. PATIENT SUMMARY: The current supply of and increased demand for bacillus Calmette-Guérin (BCG), used in the treatment of bladder cancer, have led to repeated BCG shortages. One way to address this is to provide a reduced BCG dose to allow more patients to be treated. In this study we found that BCG viability remains clinically relevant up to 72 h after reconstitution, thus allowing for more patients to be treated from a single vial.
KW - BCG shortage
KW - Bacillus Calmette-Guérin
KW - Bladder cancer
KW - Microbial viability
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U2 - 10.1016/j.euo.2020.03.004
DO - 10.1016/j.euo.2020.03.004
M3 - Article
C2 - 32475716
AN - SCOPUS:85120720880
SN - 2588-9311
VL - 4
SP - 826
EP - 828
JO - European Urology Oncology
JF - European Urology Oncology
IS - 5
ER -