title: Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy.
abstract: Thirty-one patients treated with mesenchymal stromal cells (MSCs) for acute graft-versus-host disease (aGVHD) or hemorrhagic cystitis between 2002 and 2007 were followed to investigate predictors of outcome, immunologic effects in vivo, and long-term survival. There was no correlation between in vitro suppression by MSCs in mixed lymphocyte cultures and outcome. Soluble IL-2 receptors were measured in blood before and after MSC infusion and declined significantly during the first week after MSC infusion (P = .03). Levels of interleukin-6 and HLA-G were unaffected. Infectious complications occurred several years after recovery from aGVHD. Cytomegalovirus viral load was high, and cytomegalovirus disease was common. Among patients recovering from aGVHD, 54% died of late infections, between 4 months and 2 years after MSC treatment. No increase in leukemia relapse or graft rejection was found. Children had a better survival rate than adults (P = .005). In GVHD patients, 1-year survival was 75% in patients who received early-passage MSCs (from passages 1-2) in contrast to 21% using later passage MSCs (from passages 3-4) (P < .01). We conclude that treatment with early-passage MSCs improved survival in patients with therapy-resistant GVHD. Death from infection was common in MSC-treated patients, but there was no increase in leukemia relapse.
authors.affiliation: Haematology Centre, Department of Clinical Immunology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. lena.von.bahr@ki.se
authors.forename: Lena
authors.initials: L
authors.lastname: von Bahr
authors.forename: Berit
authors.initials: B
authors.lastname: Sundberg
authors.forename: Lena
authors.initials: L
authors.lastname: Lönnies
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
authors.forename: Holger
authors.initials: H
authors.lastname: Karbach
authors.forename: Hans
authors.initials: H
authors.lastname: Hägglund
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Britt
authors.initials: B
authors.lastname: Gustafsson
authors.forename: Helen
authors.initials: H
authors.lastname: Karlsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003556:Cystitis / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007223:Infant; D007938:Leukemia / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning; D019562:Viral Load
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2