Protective conditioning for acute graft-versus-host disease.
BACKGROUND
Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans.


METHODS
Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor.


RESULTS
Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy).


CONCLUSIONS
A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.
Lowsky
Robert
R
Department of Medicine, Stanford University School of Medicine, Stanford, Calif, USA.
Takahashi
Tsuyoshi
T
Liu
Yin Ping
YP
Dejbakhsh-Jones
Sussan
S
Grumet
F Carl
FC
Shizuru
Judith A
JA
Laport
Ginna G
GG
Stockerl-Goldstein
Keith E
KE
Johnston
Laura J
LJ
Hoppe
Richard T
RT
Bloch
Daniel A
DA
Blume
Karl G
KG
Negrin
Robert S
RS
Strober
Samuel
S
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D007970:Leukopenia / Q000209:etiology; D015182:Lymphatic Irradiation; D008223:Lymphoma / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D018183:Transplantation Chimera / Q000235:genetics; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*
D000961:Antilymphocyte Serum; D016207:Cytokines