Single and multiple dose multistem (multipotent adult progenitor cell) therapy prophylaxis of acute graft-versus-host disease in myeloablative allogeneic hematopoietic cell transplantation: A phase 1 trial

Richard T. Maziarz, Timothy Devos, Carlos R. Bachier, Steven C. Goldstein, Jose F. Leis, Steven M. Devine, Gabrielle Meyers, James L. Gajewski, Johan Maertens, Robert J. Deans, Wouter Van't Hof, Hillard M. Lazarus

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)720-728
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2015

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Cell Transplantation
Graft vs Host Disease
Cell- and Tissue-Based Therapy
Stem Cells
Incidence
Safety
Chimerism
Stromal Cells
Neutrophils
Blood Platelets
Tissue Donors
Transplants
Weights and Measures
Antibodies
Therapeutics
Infection
Serum

Keywords

  • Graft-versus-host disease
  • Mesenchymal stromal cells
  • Multipotent adult progenitor cells
  • Myeloablative allogeneic hematopoietic cell transplantation
  • Phase 1

ASJC Scopus subject areas

  • Transplantation
  • Hematology

Cite this

Single and multiple dose multistem (multipotent adult progenitor cell) therapy prophylaxis of acute graft-versus-host disease in myeloablative allogeneic hematopoietic cell transplantation : A phase 1 trial. / Maziarz, Richard T.; Devos, Timothy; Bachier, Carlos R.; Goldstein, Steven C.; Leis, Jose F.; Devine, Steven M.; Meyers, Gabrielle; Gajewski, James L.; Maertens, Johan; Deans, Robert J.; Van't Hof, Wouter; Lazarus, Hillard M.

In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 4, 01.04.2015, p. 720-728.

Research output: Contribution to journalArticle

Maziarz, Richard T. ; Devos, Timothy ; Bachier, Carlos R. ; Goldstein, Steven C. ; Leis, Jose F. ; Devine, Steven M. ; Meyers, Gabrielle ; Gajewski, James L. ; Maertens, Johan ; Deans, Robert J. ; Van't Hof, Wouter ; Lazarus, Hillard M. / Single and multiple dose multistem (multipotent adult progenitor cell) therapy prophylaxis of acute graft-versus-host disease in myeloablative allogeneic hematopoietic cell transplantation : A phase 1 trial. In: Biology of Blood and Marrow Transplantation. 2015 ; Vol. 21, No. 4. pp. 720-728.
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