TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors.
A hematopoietic cell transplantation regimen was adapted from a preclinical model that used reduced-intensity conditioning (RIC) and protected against graft-versus-host disease (GVHD) by skewing residual host T-cell subsets to favor regulatory natural killer T cells. One hundred eleven patients with lymphoid (64) and myeloid (47) malignancies received RIC using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) followed by the infusion of granulocyte colony-stimulating factor-mobilized grafts. Included were 34 patients at least 60 years of age, 32 patients at high risk of lymphoma relapse after disease recurrence following prior autologous transplantation, and 51 patients at high risk of developing GVHD due to lack of a fully human leukocyte antigen (HLA)-matched related donor. Durable chimerism was achieved in 97% of patients. Cumulative probabilities of acute GVHD (grades II-IV) were 2 and 10% of patients receiving related and unrelated donor grafts. Nonrelapse mortality (NRM) at 1 year was less than 4%. Cumulative incidence of chronic GVHD was 27%. The 36-month probability of overall and event-free survival was 60% and 40%, respectively. Disease status at start of conditioning and the level of chimerism achieved after transplantation significantly impacted clinical outcome. The high incidence of sustained remission among patients with active disease at time of transplantation suggests retained graft-versus-tumor reactions. Active trial registration currently at clinicaltrials.gov under IDs of NCT00185640 and NCT00186615.
Department of Medicine, Stanford University School of Medicine, CA 94305, USA.
Holbrook E
HE
Kohrt
Brit B
BB
Turnbull
Kartoosh
K
Heydari
Judith A
JA
Shizuru
Ginna G
GG
Laport
David B
DB
Miklos
Laura J
LJ
Johnston
Sally
S
Arai
Wen-Kai
WK
Weng
Richard T
RT
Hoppe
Philip W
PW
Lavori
Karl G
KG
Blume
Robert S
RS
Negrin
Samuel
S
Strober
Robert
R
Lowsky
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D016572:Cyclosporine / Q000627:therapeutic use; D018572:Disease-Free Survival; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019520:Living Donors; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011292:Premedication; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D009173:Mycophenolic Acid