Prophylactic reinfusion of T cells for T cell-depleted allogeneic bone marrow transplantation.
To increase the graft-vs.-leukemia (GVL) effect while maintaining a low mortality from graft-vs.-host disease (GVHD), we conducted a prospective study of T cell titration for 144 patients (90 related, 54 unrelated) between June 1994 and June 1997. Following infusion of a T cell-depleted marrow graft, predetermined doses of T cells, based on the risk factors for GVHD, were administered up to 3 times if greater than a grade II acute GVHD was not seen. Graft failure occurred in three unrelated recipients (2%). Cumulative grades II-IV acute GVHD were seen in 58 +/- 9% of all recipients; 52 +/- 11% related and 75 +/- 13% unrelated. The incidence of grades II-IV acute GVHD following the third add-back (AB) of T cells 78 median days after marrow infusion was lower than that of the earlier ABs: first AB, 36 +/- 8%; second AB, 32 +/- 11%; third AB, 15 +/- 12% (p < 0.05). Chronic GVHD occurred in 56 +/- 12% of related and 79 +/- 16% of unrelated patients. Six died of acute GVHD and two died of chronic GVHD, with an overall GVHD mortality of 6 +/- 4%. In multivariate analyses, unrelated recipients and patients at low risk for GVHD who received a larger number of T cells were identified as patient groups with significant risk for acute and chronic GVHD (both p < 0.05). Unrelated transplant is also shown to be significant for GVHD-related death (p < 0.01). Relapse-free survival of patients with leukemia was shown to be most dependent on chronic GVHD and grades II-IV acute GVHD (both p < 0.01). Anti-leukemic activity independent of GVHD was not observed.
Lee
C K
CK
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, USA.
Gingrich
R D
RD
deMagalhaes-Silverman
M
M
Hohl
R J
RJ
Joyce
J K
JK
Scott
S D
SD
Wen
B C
BC
Schlueter
A
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D020350:Graft vs Tumor Effect; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019233:Retreatment; D012307:Risk Factors; D013601:T-Lymphocytes / Q000637:transplantation*; D014184:Transplantation, Homologous