Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease

Yu Oyama*, Robert M. Craig, Ann E. Traynor, Kathleen Quigley, Laisvyde Statkute, Amy Halverson, Mary Brush, Larissa Verda, Barbara Kowalska, Nela Krosnjar, Morris Kletzel, Peter F. Whitington, Richard K. Burt

*Corresponding author for this work

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Background & Aims: Crohn's disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or an increase in mortality in refractory cases, a new treatment approach is needed. In theory, maximum immune ablation by autologous hematopoietic stem cell transplantation (HSCT) can induce a remission. Methods: We conducted a phase 1 HSCT study in 12 patients with refractory CD. Candidates were younger than 60 years of age with a Crohn's Disease Activity Index (CDAI) of 250-400 despite conventional therapies including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34+ enriched. The immune ablative (conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin. Results: The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range, 8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range, 250-358). Symptoms and CDAI improved before hospital discharge, whereas radiographic and colonoscopy findings improved gradually over months to years following HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI ≤150. After a median follow-up of 18.5 months (range, 7-37 months), only one patient has developed a recurrence of active CD, which occurred 15 months after HSCT. Conclusions: Autologous HSCT may be performed safely and has a marked salutary effect on CD activity. A randomized study will be needed to confirm the efficacy of this therapy.

Original languageEnglish (US)
Pages (from-to)552-563
Number of pages12
JournalGastroenterology
Volume128
Issue number3
DOIs
StatePublished - Jan 1 2005

Fingerprint

Hematopoietic Stem Cell Transplantation
Crohn Disease
Cyclophosphamide
Fever
Antilymphocyte Serum
Anorexia
Granulocyte Colony-Stimulating Factor
Colonoscopy
Nausea
Horses
Vomiting
Gastrointestinal Tract
Diarrhea
Neutrophils
Therapeutics
Blood Platelets
Morbidity
Recurrence
Mortality

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Oyama, Yu ; Craig, Robert M. ; Traynor, Ann E. ; Quigley, Kathleen ; Statkute, Laisvyde ; Halverson, Amy ; Brush, Mary ; Verda, Larissa ; Kowalska, Barbara ; Krosnjar, Nela ; Kletzel, Morris ; Whitington, Peter F. ; Burt, Richard K. / Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. In: Gastroenterology. 2005 ; Vol. 128, No. 3. pp. 552-563.
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abstract = "Background & Aims: Crohn's disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or an increase in mortality in refractory cases, a new treatment approach is needed. In theory, maximum immune ablation by autologous hematopoietic stem cell transplantation (HSCT) can induce a remission. Methods: We conducted a phase 1 HSCT study in 12 patients with refractory CD. Candidates were younger than 60 years of age with a Crohn's Disease Activity Index (CDAI) of 250-400 despite conventional therapies including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34+ enriched. The immune ablative (conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin. Results: The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range, 8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range, 250-358). Symptoms and CDAI improved before hospital discharge, whereas radiographic and colonoscopy findings improved gradually over months to years following HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI ≤150. After a median follow-up of 18.5 months (range, 7-37 months), only one patient has developed a recurrence of active CD, which occurred 15 months after HSCT. Conclusions: Autologous HSCT may be performed safely and has a marked salutary effect on CD activity. A randomized study will be needed to confirm the efficacy of this therapy.",
author = "Yu Oyama and Craig, {Robert M.} and Traynor, {Ann E.} and Kathleen Quigley and Laisvyde Statkute and Amy Halverson and Mary Brush and Larissa Verda and Barbara Kowalska and Nela Krosnjar and Morris Kletzel and Whitington, {Peter F.} and Burt, {Richard K.}",
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Oyama, Y, Craig, RM, Traynor, AE, Quigley, K, Statkute, L, Halverson, A, Brush, M, Verda, L, Kowalska, B, Krosnjar, N, Kletzel, M, Whitington, PF & Burt, RK 2005, 'Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease', Gastroenterology, vol. 128, no. 3, pp. 552-563. https://doi.org/10.1053/j.gastro.2004.11.051

Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. / Oyama, Yu; Craig, Robert M.; Traynor, Ann E.; Quigley, Kathleen; Statkute, Laisvyde; Halverson, Amy; Brush, Mary; Verda, Larissa; Kowalska, Barbara; Krosnjar, Nela; Kletzel, Morris; Whitington, Peter F.; Burt, Richard K.

In: Gastroenterology, Vol. 128, No. 3, 01.01.2005, p. 552-563.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease

AU - Oyama, Yu

AU - Craig, Robert M.

AU - Traynor, Ann E.

AU - Quigley, Kathleen

AU - Statkute, Laisvyde

AU - Halverson, Amy

AU - Brush, Mary

AU - Verda, Larissa

AU - Kowalska, Barbara

AU - Krosnjar, Nela

AU - Kletzel, Morris

AU - Whitington, Peter F.

AU - Burt, Richard K.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Background & Aims: Crohn's disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or an increase in mortality in refractory cases, a new treatment approach is needed. In theory, maximum immune ablation by autologous hematopoietic stem cell transplantation (HSCT) can induce a remission. Methods: We conducted a phase 1 HSCT study in 12 patients with refractory CD. Candidates were younger than 60 years of age with a Crohn's Disease Activity Index (CDAI) of 250-400 despite conventional therapies including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34+ enriched. The immune ablative (conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin. Results: The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range, 8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range, 250-358). Symptoms and CDAI improved before hospital discharge, whereas radiographic and colonoscopy findings improved gradually over months to years following HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI ≤150. After a median follow-up of 18.5 months (range, 7-37 months), only one patient has developed a recurrence of active CD, which occurred 15 months after HSCT. Conclusions: Autologous HSCT may be performed safely and has a marked salutary effect on CD activity. A randomized study will be needed to confirm the efficacy of this therapy.

AB - Background & Aims: Crohn's disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or an increase in mortality in refractory cases, a new treatment approach is needed. In theory, maximum immune ablation by autologous hematopoietic stem cell transplantation (HSCT) can induce a remission. Methods: We conducted a phase 1 HSCT study in 12 patients with refractory CD. Candidates were younger than 60 years of age with a Crohn's Disease Activity Index (CDAI) of 250-400 despite conventional therapies including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34+ enriched. The immune ablative (conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin. Results: The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range, 8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range, 250-358). Symptoms and CDAI improved before hospital discharge, whereas radiographic and colonoscopy findings improved gradually over months to years following HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI ≤150. After a median follow-up of 18.5 months (range, 7-37 months), only one patient has developed a recurrence of active CD, which occurred 15 months after HSCT. Conclusions: Autologous HSCT may be performed safely and has a marked salutary effect on CD activity. A randomized study will be needed to confirm the efficacy of this therapy.

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