122: Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon

Abstract

Purpose: Mesenchymal stem cells (MSC) can differentiate to several mesenchymal tissues and have been suggested to be used for tissue repair. We explored the possibility to use MSCs to heal chemoirradiation therapy-induced tissue toxicity.Patients and Methods: Ten patients, median age 48 (13-64), who had undergone allogeneic hematopoietic stem cell transplantation (ASCT) were included. Seven had severe hemorrhagic cystitis (HC), two had pneumomediastinum and one had recurrent perforated colon diverticulitis and peritonitis. MSC were HLA- mismatched (n=11), from haploidentical donors (n=3) or siblings (n=2). Median MSC cell dose was 1.0 (range 0.7-2) × 106/kg. MSC were infused i.v. One infusion was given to six patients, two infusions to three and three infusions to one patient. A sensitive nested PCR method for HLA alleles, sensitivity 10-5 - 10-6, was used to detect residual MSC donor DNA in various tissues.Results: Two patients with grades 4-5 HC had decreased transfusion requirements after MSC infusion, but died of multi-organ failure. In one patient, MSC donor DNA was demonstrated in the urinary bladder. In five patients, with moderate to severe grades 2-3 HC, urine cleared after MSC infusion. In two patients, pneumomediastinum disappeared after MSC infusions. A patient with steroid-resistant graft-versus-host disease of the gut experienced perforated diverticulitis and peritonitis that was reversed twice by MSC. Five patients died from infections and three are alive 5, 10 and 16 months after ASCT.Conclusion: MSC is a novel therapy for therapy-induced tissue toxicity that deserves further evaluation. Purpose: Mesenchymal stem cells (MSC) can differentiate to several mesenchymal tissues and have been suggested to be used for tissue repair. We explored the possibility to use MSCs to heal chemoirradiation therapy-induced tissue toxicity. Patients and Methods: Ten patients, median age 48 (13-64), who had undergone allogeneic hematopoietic stem cell transplantation (ASCT) were included. Seven had severe hemorrhagic cystitis (HC), two had pneumomediastinum and one had recurrent perforated colon diverticulitis and peritonitis. MSC were HLA- mismatched (n=11), from haploidentical donors (n=3) or siblings (n=2). Median MSC cell dose was 1.0 (range 0.7-2) × 106/kg. MSC were infused i.v. One infusion was given to six patients, two infusions to three and three infusions to one patient. A sensitive nested PCR method for HLA alleles, sensitivity 10-5 - 10-6, was used to detect residual MSC donor DNA in various tissues. Results: Two patients with grades 4-5 HC had decreased transfusion requirements after MSC infusion, but died of multi-organ failure. In one patient, MSC donor DNA was demonstrated in the urinary bladder. In five patients, with moderate to severe grades 2-3 HC, urine cleared after MSC infusion. In two patients, pneumomediastinum disappeared after MSC infusions. A patient with steroid-resistant graft-versus-host disease of the gut experienced perforated diverticulitis and peritonitis that was reversed twice by MSC. Five patients died from infections and three are alive 5, 10 and 16 months after ASCT. Conclusion: MSC is a novel therapy for therapy-induced tissue toxicity that deserves further evaluation.