Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of pathology and laboratory medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Eur Urol Oncol. 2021 Oct;4(5):826-828. doi: 10.1016/j.euo.2020.03.004. Epub 2020 May 29.
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.
卡介苗（BCG）一直存在供应短缺的情况，而 BCG 是治疗高级别非肌肉浸润性膀胱癌（NMIBC）患者的金标准免疫疗法。一些组织已经发布了应对这一短缺的指南，包括使用分剂量 BCG，即一管可以治疗多达三名患者。然而，由于建议在复溶后 2 小时内使用 BCG，这种策略在现实环境中的物流实施受到了阻碍。我们评估了 BCG 的菌落形成单位（CFU）活力，并证明在复溶后至少 8 小时内活力保持不变（第 1 批产品在 8 小时时下降 9.1%[p=0.3]，第 2 批产品下降 4.8%[p=0.2]）。虽然 24 小时时的活力较低，但并未降至将 BCG 剂量减少三分之一（第 1 批产品为 67%，第 2 批产品为 60%）以下的水平，并且至少在 72 小时内仍接近 50%。使用 BCG 与白细胞共培养的体外模型与 BCG 敏感细胞系（RT4-V6），在 72 小时时未发现 BCG 的细胞毒性潜力下降。在短缺时期，BCG 小瓶可以在复溶后至少 8 小时（甚至 72 小时）内进行分装和给药，从而使更多患者受益于 BCG，同时减少对临床实践物流的压力。患者总结：由于用于治疗膀胱癌的卡介苗（BCG）的供应增加和需求增加，导致 BCG 反复短缺。解决此问题的一种方法是提供减少的 BCG 剂量，从而可以治疗更多的患者。在这项研究中，我们发现 BCG 的活力在复溶后长达 72 小时仍然具有临床相关性，因此可以从一个小瓶中治疗更多的患者。
