Induction of remission of severe and refractory rheumatoid arthritis by allogeneic mixed chimerism.
This report describes the first allogeneic hematopoietic stem cell transplantation (HSCT) performed for the indication of rheumatoid arthritis (RA). We used nonmyeloablative allogeneic HSCT to treat a 52-year-old woman who had treatment-refractory RA and a poor prognosis (24 swollen and 38 involved joints). She was treated with fludarabine, cyclophosphamide, CAMPATH-1H, and CD34-selected HSCT (8 million CD34+ donor cells/kg); the donor was the patient's HLA-matched, rheumatoid factor-negative sister. One year post-HSCT, the patient has had no infection except dermatomal varicella-zoster virus infection and no acute or chronic graft-versus-host disease (GVHD). Her RA has remained in remission with no immunosuppressive or immunomodulatory medications. The patient is a mixed chimera, with 55% donor T (CD3+) cells and 70% donor myeloid (CD33+) cells. This is the first published report of allogeneic HSCT performed for the indication of RA. Mixed chimerism has resulted in marked amelioration of RA, without GVHD.
Burt
Richard K
RK
Division of Immunotherapy, Northwestern University School of Medicine, Chicago, Illinois 60611, USA. rburt@northwestern.edu
Oyama
Yu
Y
Verda
Larissa
L
Quigley
Kathleen
K
Brush
Mary
M
Yaung
Kimberly
K
Statkute
Laisvyde
L
Traynor
Ann
A
Barr
Walter G
WG
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D017252:CD3 Complex / Q000032:analysis; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008875:Middle Aged; D063268:Sialic Acid Binding Ig-like Lectin 3; D018183:Transplantation Chimera; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018501:Antirheumatic Agents; D017252:CD3 Complex; C571163:CD33 protein, human; D007166:Immunosuppressive Agents; D063268:Sialic Acid Binding Ig-like Lectin 3; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine