Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer.
BACKGROUND
Allogeneic stem-cell transplantation (allo-SCT) can induce curative graft-versus-leukemia reactions for hematologic malignancies through allogeneic immunity. Because the gastrointestinal tract is a target of graft-versus-host disease (GvHD), colorectal cancer might be a candidate for allo-SCT.


METHODS
Four patients with metastatic colorectal cancer underwent reduced-intensity stem-cell transplantation (RIST) in the National Cancer Center Hospital between July 2002 and February 2003. Three patients received transplants from an human leukocyte antigen (HLA)-identical related donor, and the remaining patient received selected CD34-positive cells from a two-loci HLA-mismatched donor. The basis of preparative regimen was busulfan 4 mg/kg for 2 days and fludarabine 25 mg/kg for 6 days.


RESULTS
All the patients tolerated the preparative regimen and achieved engraftment without significant toxicities. All developed acute or chronic GvHD. Although serum levels of CA19-9 and carcinoembryonic antigen were transiently elevated after RIST in all the patients, the levels subsequently decreased below the levels from before RIST in all but one patient. Three had measurable lesions before RIST, one achieved partial response, and the others stable disease, which was durable for 120 and 60 days. Three patients died; the causes of death were progressive disease, GvHD, and accident. Postmortem examination was obtained for two patients; in one patient, the peritoneal metastatic lesions macroscopically disappeared, and in the other patient, the supraclavicular lymph node disappeared while the other measurable lesions remained stable.


CONCLUSIONS
All the patients showed some evidence suggesting the presence of a graft-versus-tumor effect for colorectal cancer, which should be confirmed in a future prospective trial.
Kojima
Rie
R
Hematopoietic Stem Cell Transplant Unit, the National Cancer Center Hospital, Tokyo, Japan.
Kami
Masahiro
M
Hori
Akiko
A
Murashige
Naoko
N
Ohnishi
Mutsuko
M
Kim
Sung-Won
SW
Hamaki
Tamae
T
Kishi
Yukiko
Y
Tsutsumi
Yutaka
Y
Masauzi
Nobuo
N
Heike
Yuji
Y
Mori
Shin-Ichiro
S
Kobayashi
Kazuhiko
K
Masuo
Shigeru
S
Tanosaki
Ryuji
R
Takaue
Yoichi
Y
D000328:Adult; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology* / Q000601:surgery* / Q000628:therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000601:surgery; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen