Nonmyeloablative allogeneic hematopoietic stem cell transplantation as immunotherapy for pancreatic cancer.
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.
Abe
Yasunobu
Y
Department of Medicine and Bioregulatory Science, Kyushu University, Fukuoka, Japan. abey@intmed3.med.kyushu-u.ac.jp
Ito
Tetsuhide
T
Baba
Eishi
E
Nagafuji
Koji
K
Kawabe
Ken
K
Choi
Ilseung
I
Arita
Yoshiyuki
Y
Miyamoto
Toshihiro
T
Teshima
Takanori
T
Nakano
Shuji
S
Harada
Mine
M
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000378:metabolism / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010190:Pancreatic Neoplasms / Q000628:therapy*; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine