Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease.
The unique immunomodulatory properties of mesenchymal stem cells (MSCs) make them a rationale agent to investigate for graft-versus-host disease (GVHD). Human MSCs were used to treat de novo acute GVHD (aGVHD). Patients with grades II-IV GVHD were randomized to receive 2 treatments of human MSCs (Prochymal(R)) at a dose of either 2 or 8 million MSCs/kg in combination with corticosteroids. Patients received GVHD prophylaxis with tacrolimus, cyclosporine, (CsA) or mycophenolate mofetil (MMF). Study endpoints included safety of Prochymal administration, induction of response to Prochymal, and overall response of aGVHD by day 28, and long-term safety. Thirty-two patients were enrolled, with 31 evaluable: 21 males, 10 females; median age 52 years (range: 34-67). Twenty-one patients had grade II, 8 had grade III, and 3 had grade IV aGVHD. Ninety-four percent of patients had an initial response to Prochymal (77% complete response [CR] and 16% partial response [PR]). No infusional toxicities or ectopic tissue formations were reported. There was no difference with respect to safety or efficacy between the low and high Prochymal dose. In conclusion, Prochymal can be infused safely into patients with aGVHD and induces response in a high proportion of GVHD patients.
Kebriaei
Partow
P
Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. pkebriae@mdanderson.org
Isola
Luis
L
Bahceci
Erkut
E
Holland
Kent
K
Rowley
Scott
S
McGuirk
Joseph
J
Devetten
Marcel
M
Jansen
Jan
J
Herzig
Roger
R
Schuster
Michael
M
Monroy
Rod
R
Uberti
Joseph
J
D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016559:Tacrolimus / Q000008:administration & dosage
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus