Allogeneic marrow transplantation in patients with severe systemic sclerosis: resolution of dermal fibrosis.
OBJECTIVE
To evaluate the safety and efficacy of allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning in patients with severe systemic sclerosis (SSc).


METHODS
Eligibility criteria for the study included SSc patients with features indicative of a poor prognosis. The myeloablative conditioning regimen included busulfan, cyclophosphamide, and antithymocyte globulin. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate. Bone marrow was transplanted from HLA-identical siblings.


RESULTS
Two patients with diffuse cutaneous SSc and lung involvement who were refractory to conventional immunosuppressive treatment were enrolled in the study. In patient 1, there were no complications related to the conditioning regimen, and GVHD did not develop after transplantation. At 5 years after HCT, there was nearly complete resolution of the scleroderma and marked improvement in physical functioning. Internal organ function improved (lung) or remained stable. On examination of serial skin biopsy samples, there was resolution of the dermal fibrosis. Patient 2 experienced skin toxicity from the conditioning regimen and hypertensive crisis that was likely related to high-dose corticosteroids given for treatment of GVHD. Although this patient experienced an improvement in scleroderma and overall functioning, a fatal opportunistic infection developed 17 months after HCT.


CONCLUSIONS
Allogeneic HCT may result in sustained remission of SSc. GVHD and opportunistic infections are the major risks associated with allogeneic HCT for SSc, as for allogeneic HCT in general.
Nash
Richard A
RA
Fred Hutchinson Cancer Research Center, Seattle, WA, USA. rnash@fhcrc.org
McSweeney
Peter A
PA
Nelson
J Lee
JL
Wener
Mark
M
Georges
George E
GE
Langston
Amelia A
AA
Shulman
Howard
H
Sullivan
Keith M
KM
Lee
Julie
J
Henstorf
Gretchen
G
Storb
Rainer
R
Furst
Daniel E
DE
D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000601:surgery*; D012867:Skin / Q000473:pathology*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D003520:Cyclophosphamide; D002066:Busulfan; D008727:Methotrexate