title: Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer.
abstract: 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.
authors.affiliation: Hematopoietic Stem Cell Transplant Unit, the National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kojima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kami
authors.forename: Akiko
authors.initials: A
authors.lastname: Hori
authors.forename: Naoko
authors.initials: N
authors.lastname: Murashige
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Tamae
authors.initials: T
authors.lastname: Hamaki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kishi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Masauzi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Heike
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Mori
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Masuo
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tanosaki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takaue
mesh_terms: 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
chemical_list: D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen