Pulmonology Xagena

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Multidrug and extensively drug-resistant tuberculosis: autologous mesenchymal stromal cell infusion as adjunct treatment

Novel treatment options are urgently needed for multidrug-resistant ( MDR ) and extensively drug-resistant ( XDR ) tuberculosis, which are associated with immune dysfunction and poor treatment outcomes.
Mesenchymal stromal cells ( MSCs ) are immunomodulatory and adjunct autologous treatment with bone marrow-derived MSCs might improve clinical outcome by transforming chronic inflammation into productive immune responses.
The aim was to assess the safety of infusion of autologous mesenchymal stromal cells as an adjunct treatment in patients with tuberculosis.

30 patients with microbiologically confirmed MDR or XDR tuberculosis were treated with single-dose autologous bone marrow-derived MSCs ( aimed for 1×106 cells per kg ), within 4 weeks of the start of antituberculosis-drug treatment in a specialist centre in Minsk, Belarus.
Inclusion patients were those with pulmonary tuberculosis confirmed by sputum smear microscopy, culture, or both; MDR or XDR tuberculosis confirmed by drug-susceptibility testing to first-line and second-line drugs; age older than 21 years to 65 years or younger; and absence of lesion compatible with a malignant process or ongoing tuberculosis in organs other than the lungs and pleura.
In addition to the inclusion criteria, patients were excluded if they were pregnant, coinfected with HIV, or infected with hepatitis B, C, or both.

The primary endpoint was safety measured by MSC-infusion related events; any tuberculosis-related event within the 6 month observation period that related to a worsening of the underlying infectious disease, measured by conversion of Mycobacterium tuberculosis culture or microscopic examination; or any adverse event defined clinically or by changes in blood haematology and biochemistry variables, measured monthly for 6 months after mesenchymal stromal cells infusion per protocol.

The most common ( grade 1 or 2 ) adverse events were high cholesterol levels ( 14 of 30 patients ), nausea ( 11 of 30 patients ), and lymphopenia or diarrhoea ( ten of 30 patients ).
There were no serious adverse events reported.
Two grade 3 events were recorded that were transitory ( ie, increased plasma potassium ion concentrations in one patient and a transitory grade 3 gamma-glutamyltransferase elevation in another patient ).

In conclusion, mesenchymal stromal cells as an adjunct therapy are safe and can now be explored further for the treatment of patients with MDR or XDR tuberculosis in combination with standard drug regimens.
Adjunct treatment with mesenchymal stromal cells needs to be evaluated in controlled phase 2 trials to assess effects on immune responses and clinical and microbiological outcomes. ( Xagena )

Skrahin A et al, Lancet Respiratory Medicine 2014; 2: 108–122