Sequential third-party mesenchymal stromal cell therapy for refractory acute graft-versus-host disease

Biol Blood Marrow Transplant. 2014 Oct;20(10):1580-5. doi: 10.1016/j.bbmt.2014.06.015. Epub 2014 Jun 19.

Abstract

We evaluated the feasibility, safety, and efficacy of the administration of 4 sequential doses (intravenously administered on days 1, 4, 11, and 18) of cryopreserved bone marrow-derived mesenchymal stromal cells (MSC) expanded with platelet lysate and obtained from third-party donors as a second-line treatment for steroid-refractory acute graft-versus-host (aGVHD) disease in a series of 25 patients. All patients received at least 2 doses of MSC, whereas 21 received 3 doses and 18 received the initially planned 4 doses. Because of the achievement of partial response, 4 patients received additional doses of MSC. Median single cell dose administered was 1.1 × 10(6) MSC/kg of recipient body weight. There were no adverse events related to the MSC infusion in the 99 procedures performed, with the exception of a cardiac ischemic event that occurred twice in a patient with prior history of cardiac ischemia. Response to MSC at 60 days after the first dose was evaluable in 24 patients. Seventeen patients (71%) responded (11 complete and 6 partial responses), with a median time to response of 28 days after the first MSC dose, whereas 7 patients did not respond. In summary, we can conclude that sequential cryopreserved third-party MSC therapy administered on days 1, 4, 11, and 18 is a safe procedure for patients with steroid-refractory aGVHD. This strategy may provide a high rate of overall responses of aGVHD with a low toxicity profile.

Keywords: Graft-versus-host disease (GVHD); Mesenchymal stromal cells (MSC).

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Blood Platelets / chemistry
  • Cell Count
  • Cryopreservation*
  • Drug Resistance, Neoplasm
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / therapy*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Middle Aged
  • Prospective Studies
  • Steroids / therapeutic use
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Steroids