Mesenchymal Stem Cell As a Salvage Treatment for Patients with Refractory Bronchiolitis Obliterans Syndrome after Allogenetic Hematopoietic Stem Cell Transplantation

Abstract

Background Bronchiolitis obliterans syndrome (BOS) is the most detrimental late pulmonary complications after allogeneic hematopoietic stem cell transplantation, as it is characterized by non-responsiveness to treatment, leading to high morbidity and mortality. Mesenchymal stem cell (MSC) has been considered as an effective treatment for refractory aGVHD, but the response to treat cGVHD, especially refractory BOS, is rarely reported. This study evaluated the efficacy of MSC from bone marrow (BM) of a third-party donor to BOS patients.Methods Fifty-three patients with refractory BOS were enrolled in our prospective study, including 29 patients in MSC group and 24 patients in non-MSC group. All patients had previously failed to at least 2 lines of immunosuppressive therapy. MSCs were given at a median dose of 1×106 cells/kg once weekly for 4 weeks as one cycle treatment. The responsiveness of MSC was evaluated after one cycle, non-responsive patients discontinued MSC treatments, others continued to accept another cycle of MSC treatments.Results Fifty-three patients developed BOS at a median time of 172 days (range, 94 to 398). After a total of 169 doses of MSC were administered, with a median of 6 (range:3-11) doses per patient, the overall response (OR) rate in MSC group was 75.9%, including CR in 13.8% and partial response (PR) in 62.1%. Compared with MSC group, OR rate in non-MSC group was 16.7%, including CR in 4.2% and PR in 12.5% (P=0.000; P=0.233; P=0.000, respectively). Furthermore, the efficacy of MSC to refractory BOS was significantly related with the severity of pulmonary function (mild VS severity, P=0.039). During the median follow-up time of 814 (range:228-2499) days post-transplantation, 7 patients were dead in MSC group, while 18 patients died in non-MSC group. The 5-year OS post-transplantation in MSC group were 68.6%±5.7%, compared with 21.2%±7.1% in non-MSC group (P=0.033). No patients experienced any toxic side effects and other secondary tumors after MSC treatment.Conclusion MSC derived from BM of third-party donors is a promising treatment for patients with refractory BOS. DisclosuresNo relevant conflicts of interest to declare.