TY - JOUR
T1 - Single and multiple dose multistem (multipotent adult progenitor cell) therapy prophylaxis of acute graft-versus-host disease in myeloablative allogeneic hematopoietic cell transplantation
T2 - A phase 1 trial
AU - Maziarz, Richard T.
AU - Devos, Timothy
AU - Bachier, Carlos R.
AU - Goldstein, Steven C.
AU - Leis, Jose F.
AU - Devine, Steven M.
AU - Meyers, Gabrielle
AU - Gajewski, James L.
AU - Maertens, Johan
AU - Deans, Robert J.
AU - Van't Hof, Wouter
AU - Lazarus, Hillard M.
N1 - Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after myeloablative allogeneic hematopoietic cell transplantation (HCT). Patients received increasing doses of MAPC (1, 5, or 10 million cells per kilogram recipient weight) as a single i.v. dose on day+2 after HCT (n= 18), or once weekly for up to 5 doses (1 or 5 million cells per kilogram; n= 18). Infusional and regimen-related toxicities were assessed for 30 days after the last MAPC dose. Of 36 allogeneic HCT donors (17 related and 19 unrelated), 35 were 6/6 HLA matched. MAPC infusions were well tolerated without associated infusional toxicity, graft failure, or increased incidence of infection. Median times to neutrophil (n= 36) and platelet (n= 31) engraftment were 15 (range, 11 to 25) and 16 (range, 11 to 41) days, respectively. The overall cumulative incidences of grades II to IV and III and IV acute graft-versus-host disease (GVHD) at day 100 were 37% and 14%, respectively (n= 36). In the group that received the highest single MAPC dose (10 million cells/kg), day 100 incidence of grade II to IV GVHD was 11.1% (1 of 9) with no observed cases of grade III and IV GVHD. We found no evidence for MHC class II allogeneic antibody induction, although some patients showed an increase in serum anticlass I titers compared with baseline. MAPC contribution to blood chimerism was negligible. These phase I data support the safety of stromal stem cell therapy and suggest that MAPC should be tested prospectively as a novel therapeutic option for GVHD prophylaxis after HCT.
AB - We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after myeloablative allogeneic hematopoietic cell transplantation (HCT). Patients received increasing doses of MAPC (1, 5, or 10 million cells per kilogram recipient weight) as a single i.v. dose on day+2 after HCT (n= 18), or once weekly for up to 5 doses (1 or 5 million cells per kilogram; n= 18). Infusional and regimen-related toxicities were assessed for 30 days after the last MAPC dose. Of 36 allogeneic HCT donors (17 related and 19 unrelated), 35 were 6/6 HLA matched. MAPC infusions were well tolerated without associated infusional toxicity, graft failure, or increased incidence of infection. Median times to neutrophil (n= 36) and platelet (n= 31) engraftment were 15 (range, 11 to 25) and 16 (range, 11 to 41) days, respectively. The overall cumulative incidences of grades II to IV and III and IV acute graft-versus-host disease (GVHD) at day 100 were 37% and 14%, respectively (n= 36). In the group that received the highest single MAPC dose (10 million cells/kg), day 100 incidence of grade II to IV GVHD was 11.1% (1 of 9) with no observed cases of grade III and IV GVHD. We found no evidence for MHC class II allogeneic antibody induction, although some patients showed an increase in serum anticlass I titers compared with baseline. MAPC contribution to blood chimerism was negligible. These phase I data support the safety of stromal stem cell therapy and suggest that MAPC should be tested prospectively as a novel therapeutic option for GVHD prophylaxis after HCT.
KW - Graft-versus-host disease
KW - Mesenchymal stromal cells
KW - Multipotent adult progenitor cells
KW - Myeloablative allogeneic hematopoietic cell transplantation
KW - Phase 1
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UR - http://www.scopus.com/inward/citedby.url?scp=84924273627&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2014.12.025
DO - 10.1016/j.bbmt.2014.12.025
M3 - Article
C2 - 25555450
AN - SCOPUS:84924273627
SN - 1083-8791
VL - 21
SP - 720
EP - 728
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -