Nonmyeloablative allogeneic hematopoietic stem cell transplantation as immunotherapy for pancreatic cancer

Pancreas. 2009 Oct;38(7):815-9. doi: 10.1097/MPA.0b013e3181b576ee.

Abstract

Objective: Advanced unresectable pancreatic cancer has an extremely poor prognosis despite intensive chemotherapy. As a new therapeutic modality, we investigated nonmyeloablative allogeneic hematopoietic stem cell transplantation from a related donor.

Methods: Five patients with chemotherapy-resistant pancreatic cancer received allogeneic peripheral blood stem cell transplantation after a conditioning regimen consisting of low-dose total body irradiation and fludarabine. The prophylaxis for graft-versus-host disease consisted of mycophenolate mofetil and cyclosporine.

Results: The median age of the 5 patients was 54 years, and the median duration from diagnosis to nonmyeloablative allogeneic hematopoietic stem cell transplantation was 10 months. Three of the 5 patients achieved complete donor chimerism of peripheral T cells, at a median time of day 42. Acute graft-versus-host disease developed in 3 patients: grade 2 in 2 patients and grade 1 in 1. Tumor reduction was observed in 2 patients: 1 patient showed disappearance of the pancreatic tumor, and the other patient showed approximately 20% reduction of the tumor. Marked elevation of tumor necrosis factor alpha was observed as the tumor regressed.

Conclusions: Although advanced pancreatic cancer progresses rapidly, some graft-versus-tumor effects and pivotal role of tumor necrosis factor alpha were suggested. To obtain the durable response, patient selection and new strategies become important.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclosporine / administration & dosage
  • Female
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunotherapy / methods*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Pancreatic Neoplasms / therapy*
  • Time Factors
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Tumor Necrosis Factor-alpha / metabolism
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Whole-Body Irradiation

Substances

  • Antineoplastic Agents
  • Tumor Necrosis Factor-alpha
  • Cyclosporine
  • Vidarabine
  • Mycophenolic Acid
  • fludarabine