Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses.
Data on the application of donor lymphocyte infusions (DLIs) following reduced-intensity transplantation (RIT) remain limited. Persistence of host antigen-presenting cells might increase the efficacy or toxicity of cellular immunotherapies. We report the results of dose-escalating DLIs in 46 patients undergoing RIT, who received a total of 109 infusions to treat mixed chimerism or residual or progressive disease. Diagnoses were myeloma (n = 19), Hodgkin lymphoma (n = 13), non-Hodgkin lymphoma (n = 10), and other (n = 4). Thirty-two had an HLA-matched family donor and 14 an unrelated donor. Grades II to IV graft-versus-host disease (GVHD) occurred in 5 sibling and 7 unrelated donor recipients. GVHD was more common (P =.002), occurred at lower T-cell doses, and was more severe in the unrelated donor cohort. Conversion from mixed to multilineage full donor chimerism occurred in 30 of 35 evaluable patients. Presence of mixed chimerism in the granulocyte lineage at the time of DLI did not predict for chimerism response or GVHD. Disease responses occurred in 63% of patients with myeloma and 70% of those with Hodgkin lymphoma and were not predicted by changes in chimerism. These data support the presence of clinically relevant graft-versus-Hodgkin activity and indicate that DLI may be associated with a significantly increased toxicity in unrelated compared to sibling donor transplant recipients receiving identical treatment protocols.
Department of Haematology, University College Hospital, 98 Chenies Mews, London, WC1E 6HX, United Kingdom. kpeggs@hotmail.com
Karl S
KS
Peggs
Kirsty
K
Thomson
Daniel P
DP
Hart
Johanne
J
Geary
Emma C
EC
Morris
Kwee
K
Yong
Anthony H
AH
Goldstone
David C
DC
Linch
Stephen
S
Mackinnon
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology; D017710:Lymphocyte Transfusion / Q000009:adverse effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018183:Transplantation Chimera; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D000074323:Alemtuzumab