Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer

Rie Kojima, Masahiro Kami, Akiko Hori, Naoko Murashige, Mutsuko Ohnishi, Sung Won Kim, Tamae Hamaki, Yukiko Kishi, Yutaka Tsutsumi, Nobuo Masauzi, Yuji Heike, Shin Ichiro Mori, Kazuhiko Kobayashi, Shigeru Masuo, Ryuji Tanosaki, Yoichi Takaue

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1740-1746
Number of pages7
JournalTransplantation
Volume78
Issue number12
DOIs
Publication statusPublished - 2004 Dec 27
Externally publishedYes

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Hematopoietic Stem Cell Transplantation
Immunotherapy
Colorectal Neoplasms
Stem Cell Transplantation
Graft vs Host Disease
HLA Antigens
Transplants
Tissue Donors
Cancer Care Facilities
Busulfan
Carcinoembryonic Antigen
Hematologic Neoplasms
Accidents
Gastrointestinal Tract
Cause of Death
Autopsy
Immunity
Leukemia
Lymph Nodes

Keywords

  • Allogeneic immunity
  • Carcinoembryonic antigen
  • Fludarabine
  • Graft-versus-host disease
  • Graft-versus-tumor effect

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer. / Kojima, Rie; Kami, Masahiro; Hori, Akiko; Murashige, Naoko; Ohnishi, Mutsuko; Kim, Sung Won; Hamaki, Tamae; Kishi, Yukiko; Tsutsumi, Yutaka; Masauzi, Nobuo; Heike, Yuji; Mori, Shin Ichiro; Kobayashi, Kazuhiko; Masuo, Shigeru; Tanosaki, Ryuji; Takaue, Yoichi.

In: Transplantation, Vol. 78, No. 12, 27.12.2004, p. 1740-1746.

Research output: Contribution to journalArticle

Kojima, R, Kami, M, Hori, A, Murashige, N, Ohnishi, M, Kim, SW, Hamaki, T, Kishi, Y, Tsutsumi, Y, Masauzi, N, Heike, Y, Mori, SI, Kobayashi, K, Masuo, S, Tanosaki, R & Takaue, Y 2004, 'Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer', Transplantation, vol. 78, no. 12, pp. 1740-1746. https://doi.org/10.1097/01.TP.0000146194.36297.4E
Kojima, Rie ; Kami, Masahiro ; Hori, Akiko ; Murashige, Naoko ; Ohnishi, Mutsuko ; Kim, Sung Won ; Hamaki, Tamae ; Kishi, Yukiko ; Tsutsumi, Yutaka ; Masauzi, Nobuo ; Heike, Yuji ; Mori, Shin Ichiro ; Kobayashi, Kazuhiko ; Masuo, Shigeru ; Tanosaki, Ryuji ; Takaue, Yoichi. / Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer. In: Transplantation. 2004 ; Vol. 78, No. 12. pp. 1740-1746.
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AU - Kojima, Rie

AU - Kami, Masahiro

AU - Hori, Akiko

AU - Murashige, Naoko

AU - Ohnishi, Mutsuko

AU - Kim, Sung Won

AU - Hamaki, Tamae

AU - Kishi, Yukiko

AU - Tsutsumi, Yutaka

AU - Masauzi, Nobuo

AU - Heike, Yuji

AU - Mori, Shin Ichiro

AU - Kobayashi, Kazuhiko

AU - Masuo, Shigeru

AU - Tanosaki, Ryuji

AU - Takaue, Yoichi

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N2 - 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.

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