Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis (M/XDR-TB): An open-label phase 1 safety trial

Novel treatment options are urgently needed for M/XDR-TB, which is associated with immune dysfunction and poor treatment outcomes. Mesenchymal stromal cells (MSCs) are immunomodulatory and adjunct treatment with autologous MSCs might improve clinical outcome by transforming chronic inflammation into productive immune responses. Our aim was to assess the safety of autologous MSC infusion as an adjunct treatment for M/XDR-TB. 30 patients with confirmed M/XDR-TB were treated with single-dose autologous bone marrow-derived MSCs, within 4 weeks of the start of anti-TB drug treatment. The primary endpoint was safety measured by MSC-infusion related events; any tuberculosis-related event within the 6 months observation period that related to a worsening of the underlying infectious disease, measured by sputum smear and culture examination; any adverse event defined clinically or by changes in hematology and biochemistry variables, measured monthly during 6 months after MSC infusion. The most common (grade 1 or 2) adverse events were nausea, lymphopenia and diarrhea. There were no serious adverse events reported. We recorded two grade 3 events that were transitory (ie, increased plasma potassium ion concentrations in one patient and γ-glutamyltransferase elevation in another one). Autologous MSCs infusion as an adjunct therapy is safe and can now be explored further for the treatment of patients with M/XDR-TB in combination with drug regimens. Adjunct treatment with MSCs needs to be evaluated in controlled phase 2 trial to assess effects on immune responses and also the clinical and microbiological outcomes.