A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease.
OBJECTIVE
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 2x10(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.
Tsukamoto
H
H
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. tsukamot@intmed1.med.kyushu-u.ac.jp
Nagafuji
K
K
Horiuchi
T
T
Miyamoto
T
T
Aoki
K
K
Takase
K
K
Henzan
H
H
Himeji
D
D
Koyama
T
T
Miyake
K
K
Inoue
Y
Y
Nakashima
H
H
Otsuka
T
T
Tanaka
Y
Y
Nagasawa
K
K
Harada
M
M
D000328:Adult; D018952:Antigens, CD34 / Q000097:blood; D001327:Autoimmune Diseases / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D003882:Dermatomyositis / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D012595:Scleroderma, Systemic / Q000628:therapy; D016896:Treatment Outcome
D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide