Bone marrow infection with bacillus Calmette-Guérin (BCG) after intravesical immunotherapy

Abstract

Instillation of bacillus Calmette-Guérin (BCG) into the urine bladder is an effective treatment of superficial bladder cancer. BCG-mediated anti-tumor activity appears to be a local phenomenon in which cell-mediated immunity, involving cytotoxic T cells, lymphokine-activated killer cells and natural killer cells, is important for the elimination of malignant cells. Serious side-effects of BCG therapy are rare; nevertheless, BCG is a live, attenuated strain of Mycobacterium (M.) bovis and may exhibit invasive properties. Both local and distant or generalized infections have been reported after treatment with BCG. We describe the case of a 68-year-old man who developed bone marrow infection with BCG two years after intravesical instillation of BCG for treatment of superficial bladder cancer. He presented with intermittent fever, weight loss and pronounced pancytopenia. A bone marrow biopsy specimen showed granulomatous inflammation and BCG was cultured from the urine. Anti-mycobacterial treatment with isoniazid, rifampicin and ethambutol (pyrazinamide is inactive against M. bovis) led to full clinical recovery of the patient.

Bacillus Calmette-Guérin (BCG) Infection Following Intravesical BCG Administration as Adjunctive Therapy For Bladder Cancer

“…Chest imaging also play a crucial role in diagnosing disseminated BCG infection and the present review suggests that CT scan should always be preferred over conventional radiography, as the latter technique failed to reveal a miliary pattern in about one-quarter of the patients eventually found to have miliary tuberculosis. 11 , 29 , 37 , 39 , 46 , 63 , 85 , 117 , 141 , 142 , 177 , 214 , 231…”

Mycobacterium Bovis BCG Strain Osteomyelitis Masquerading as Spinal Metastasis from Bladder Cancer

“…Another case developed pancytopenia from bone marrow infection with BCG two years after intravesical instillation of BCG for bladder cancer. 22 Mycobacterium bovis osteomyelitis involving a hip arthroplasty 17 and infected aortic aneurysm along with vertebral osteomyelitis also has been reported. 26 Although the systemic complications are known from the use of intravesical BCG, osteomyelitis is a rare complication and recognition of this syndrome is critical to institution of appropriate therapy and prevention of long-term complications in patients treated with intravesical BCG.…”

“…At least fifteen cases of M. bovis BCG strain osteomyelitis have been reported following intravesical therapy. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] The range for presentation post instillation varies between two weeks and 12 years. In one report, 1.5 years after diagnosis and surgical and anti-tuberculous treatment, the patient was pain-free with no functional limitations or clinical and imaging findings of recurrent infection.…”

Transitory Spontaneous Remission of Myelodysplasia in an Elderly Man while Receiving Intravesical Bacillus Calmette-Guérin for Bladder Cancer: A Case Report and Review of the Literature

“…The use of intravescial BCG has been reported to be associated with systemic autoimmune diseases, such as cyroglobulinemia vasculitis [ 17 ], autoimmune retinopathy [ 18 ], Henoch-Schonlein purpura [ 19 ], and haemophagocytic syndrome [ 20 ]. BCG has also caused a pancytopenia due to bone marrow infection, which may be delayed up to two years post-treatment [ 4 , 20 ]. This highlights that intravesical BCG may produce systemic side-effects.…”