A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease

H. Tsukamoto, K. Nagafuji, T. Horiuchi, T. Miyamoto, K. Aoki, K. Takase, H. Henzan, D. Himeji, T. Koyama, K. Miyake, Y. Inoue, H. Nakashima, T. Otsuka, Y. Tanaka, K. Nagasawa, M. Harada

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objectives: To carry out a phase I-II trial to elucidate the feasibility and efficacy of high dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) in the treatment of severe and refractory autoimmune disease (AD). Methods: Peripheral blood stem cells (PBSCs) were mobilised during haematological recovery after relatively high dose CY (2 g/m2) for 2 days, followed by administration of granulocyte colony stimulating factor. After collecting PBSCs-more than 2 × l0 6 CD34+ cells/kg-by apheresis, CD34+ cells were immunologically selected and cryopreserved. Eight patients were enrolled-five had systemic sclerosis (SSc) alone, one had SSc with systemic lupus erythematosus, one amyopathic dermatomyositis (ADM), and one Wegener's granulomatosis (WG). All of the patients were treated with high dose CY (50 mg/kg) for 4 days and autologous PBSCT. Results: Haematopoietic reconstitution was rapid and sustained. Toxicity due to the regimen included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure. However, there was no treatment related mortality. Encouraging results were obtained after autologous PBSCT. Sclerosis of the skin was markedly improved in all of the patients with SSc. Interstitial pneumonia (IP), evaluated by PaO2, serum KL-6 levels, and pulmonary high resolution computed tomography, improved significantly. In a patient with ADM, severe and progressive IP also improved markedly. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos. Conclusions: These observations suggest that high dose CY with autologous PBSCT is feasible and may be effective in the treatment of severe and refractory AD.

Original languageEnglish
Pages (from-to)508-514
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume65
Issue number4
DOIs
Publication statusPublished - Apr 1 2006

Fingerprint

Peripheral Blood Stem Cell Transplantation
Stem cells
Refractory materials
Autoimmune Diseases
Blood
Cyclophosphamide
Systemic Scleroderma
Granulomatosis with Polyangiitis
Interstitial Lung Diseases
Therapeutics
Blood Component Removal
Exophthalmos
Cystitis
Herpes Zoster
Sclerosis
Granulocyte Colony-Stimulating Factor
Granuloma
Systemic Lupus Erythematosus
Sepsis
Pneumonia

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease. / Tsukamoto, H.; Nagafuji, K.; Horiuchi, T.; Miyamoto, T.; Aoki, K.; Takase, K.; Henzan, H.; Himeji, D.; Koyama, T.; Miyake, K.; Inoue, Y.; Nakashima, H.; Otsuka, T.; Tanaka, Y.; Nagasawa, K.; Harada, M.

In: Annals of the Rheumatic Diseases, Vol. 65, No. 4, 01.04.2006, p. 508-514.

Research output: Contribution to journalArticle

Tsukamoto, H, Nagafuji, K, Horiuchi, T, Miyamoto, T, Aoki, K, Takase, K, Henzan, H, Himeji, D, Koyama, T, Miyake, K, Inoue, Y, Nakashima, H, Otsuka, T, Tanaka, Y, Nagasawa, K & Harada, M 2006, 'A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease', Annals of the Rheumatic Diseases, vol. 65, no. 4, pp. 508-514. https://doi.org/10.1136/ard.2005.037879
Tsukamoto, H. ; Nagafuji, K. ; Horiuchi, T. ; Miyamoto, T. ; Aoki, K. ; Takase, K. ; Henzan, H. ; Himeji, D. ; Koyama, T. ; Miyake, K. ; Inoue, Y. ; Nakashima, H. ; Otsuka, T. ; Tanaka, Y. ; Nagasawa, K. ; Harada, M. / A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease. In: Annals of the Rheumatic Diseases. 2006 ; Vol. 65, No. 4. pp. 508-514.
@article{fd29ce03fc024f7fb5f194e5d5f6fcaf,
title = "A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease",
abstract = "Objectives: To carry out a phase I-II trial to elucidate the feasibility and efficacy of high dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) in the treatment of severe and refractory autoimmune disease (AD). Methods: Peripheral blood stem cells (PBSCs) were mobilised during haematological recovery after relatively high dose CY (2 g/m2) for 2 days, followed by administration of granulocyte colony stimulating factor. After collecting PBSCs-more than 2 × l0 6 CD34+ cells/kg-by apheresis, CD34+ cells were immunologically selected and cryopreserved. Eight patients were enrolled-five had systemic sclerosis (SSc) alone, one had SSc with systemic lupus erythematosus, one amyopathic dermatomyositis (ADM), and one Wegener's granulomatosis (WG). All of the patients were treated with high dose CY (50 mg/kg) for 4 days and autologous PBSCT. Results: Haematopoietic reconstitution was rapid and sustained. Toxicity due to the regimen included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure. However, there was no treatment related mortality. Encouraging results were obtained after autologous PBSCT. Sclerosis of the skin was markedly improved in all of the patients with SSc. Interstitial pneumonia (IP), evaluated by PaO2, serum KL-6 levels, and pulmonary high resolution computed tomography, improved significantly. In a patient with ADM, severe and progressive IP also improved markedly. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos. Conclusions: These observations suggest that high dose CY with autologous PBSCT is feasible and may be effective in the treatment of severe and refractory AD.",
author = "H. Tsukamoto and K. Nagafuji and T. Horiuchi and T. Miyamoto and K. Aoki and K. Takase and H. Henzan and D. Himeji and T. Koyama and K. Miyake and Y. Inoue and H. Nakashima and T. Otsuka and Y. Tanaka and K. Nagasawa and M. Harada",
year = "2006",
month = "4",
day = "1",
doi = "10.1136/ard.2005.037879",
language = "English",
volume = "65",
pages = "508--514",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "4",

}

TY - JOUR

T1 - A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease

AU - Tsukamoto, H.

AU - Nagafuji, K.

AU - Horiuchi, T.

AU - Miyamoto, T.

AU - Aoki, K.

AU - Takase, K.

AU - Henzan, H.

AU - Himeji, D.

AU - Koyama, T.

AU - Miyake, K.

AU - Inoue, Y.

AU - Nakashima, H.

AU - Otsuka, T.

AU - Tanaka, Y.

AU - Nagasawa, K.

AU - Harada, M.

PY - 2006/4/1

Y1 - 2006/4/1

N2 - Objectives: To carry out a phase I-II trial to elucidate the feasibility and efficacy of high dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) in the treatment of severe and refractory autoimmune disease (AD). Methods: Peripheral blood stem cells (PBSCs) were mobilised during haematological recovery after relatively high dose CY (2 g/m2) for 2 days, followed by administration of granulocyte colony stimulating factor. After collecting PBSCs-more than 2 × l0 6 CD34+ cells/kg-by apheresis, CD34+ cells were immunologically selected and cryopreserved. Eight patients were enrolled-five had systemic sclerosis (SSc) alone, one had SSc with systemic lupus erythematosus, one amyopathic dermatomyositis (ADM), and one Wegener's granulomatosis (WG). All of the patients were treated with high dose CY (50 mg/kg) for 4 days and autologous PBSCT. Results: Haematopoietic reconstitution was rapid and sustained. Toxicity due to the regimen included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure. However, there was no treatment related mortality. Encouraging results were obtained after autologous PBSCT. Sclerosis of the skin was markedly improved in all of the patients with SSc. Interstitial pneumonia (IP), evaluated by PaO2, serum KL-6 levels, and pulmonary high resolution computed tomography, improved significantly. In a patient with ADM, severe and progressive IP also improved markedly. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos. Conclusions: These observations suggest that high dose CY with autologous PBSCT is feasible and may be effective in the treatment of severe and refractory AD.

AB - Objectives: To carry out a phase I-II trial to elucidate the feasibility and efficacy of high dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) in the treatment of severe and refractory autoimmune disease (AD). Methods: Peripheral blood stem cells (PBSCs) were mobilised during haematological recovery after relatively high dose CY (2 g/m2) for 2 days, followed by administration of granulocyte colony stimulating factor. After collecting PBSCs-more than 2 × l0 6 CD34+ cells/kg-by apheresis, CD34+ cells were immunologically selected and cryopreserved. Eight patients were enrolled-five had systemic sclerosis (SSc) alone, one had SSc with systemic lupus erythematosus, one amyopathic dermatomyositis (ADM), and one Wegener's granulomatosis (WG). All of the patients were treated with high dose CY (50 mg/kg) for 4 days and autologous PBSCT. Results: Haematopoietic reconstitution was rapid and sustained. Toxicity due to the regimen included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure. However, there was no treatment related mortality. Encouraging results were obtained after autologous PBSCT. Sclerosis of the skin was markedly improved in all of the patients with SSc. Interstitial pneumonia (IP), evaluated by PaO2, serum KL-6 levels, and pulmonary high resolution computed tomography, improved significantly. In a patient with ADM, severe and progressive IP also improved markedly. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos. Conclusions: These observations suggest that high dose CY with autologous PBSCT is feasible and may be effective in the treatment of severe and refractory AD.

UR - http://www.scopus.com/inward/record.url?scp=33645120856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645120856&partnerID=8YFLogxK

U2 - 10.1136/ard.2005.037879

DO - 10.1136/ard.2005.037879

M3 - Article

C2 - 16126798

AN - SCOPUS:33645120856

VL - 65

SP - 508

EP - 514

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 4

ER -