title: The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation.
abstract: We describe the toxicity and efficacy of donor lymphocyte infusions (DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations performed at 16 centers in the United Kingdom. The diseases treated included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia (CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9). Eighty-eight percent received stem cells from sibling donors. The patients received 130 infusions (median, 1; range, 1-4). Indications for DLI were unsatisfactory response/disease progression in 51 patients, mixed chimerism in 18, preemptive in 10, and other in 2. Graft hypoplasia was uncommon (11%). Grade II to IV graft-versus-host disease (GVHD) occurred in 23 of 81 patients (28%) and limited and extensive chronic GVHD in 5 of 69 and 18 of 69 evaluable patients (total incidence 33%). Conversion from mixed to full donor chimerism occurred in 19 of 55 evaluable patients (35%) at a median of 48 days after the DLI; partial responses occurred in 6 patients (total response rate 45%). Eighteen of 51 (35%) patients with measurable disease after stem cell transplantation had a complete response (2 molecular), and 5 a partial response (total response rate 45%). Eleven of 17 evaluable complete responders had full donor chimerism. Eight of 13 patients with follicular NHL had complete responses as did 4 of 12 patients with CML. Clinical and chimeric responses correlated strongly with acute and chronic GVHD. Forty-seven patients (58%) survive at a median of 508 days after transplantation (range, 155-1171 days) with a median Karnofsky score of 90. Thirty-four patients (42%) died at a median of 211 days after transplantation with the major causes being progressive disease (26%) and GVHD (9%). Further systematic studies are required to determine the efficacy and optimum use of DLI for patients with each disease treated by nonmyeloablative stem cell transplantation.
authors.affiliation: Adult BMT Unit, Bristol Children's Hospital, Upper Maudlin Street, Bristol BS2 8BJ, UK. dmarks@nildram.co.uk
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: Richard
authors.initials: R
authors.lastname: Lush
authors.forename: Jamie
authors.initials: J
authors.lastname: Cavenagh
authors.forename: Donald W
authors.initials: DW
authors.lastname: Milligan
authors.forename: Steven
authors.initials: S
authors.lastname: Schey
authors.forename: Anne
authors.initials: A
authors.lastname: Parker
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Clark
authors.forename: Linda
authors.initials: L
authors.lastname: Hunt
authors.forename: John
authors.initials: J
authors.lastname: Yin
authors.forename: Steven
authors.initials: S
authors.lastname: Fuller
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Vandenberghe
authors.forename: Judith
authors.initials: J
authors.lastname: Marsh
authors.forename: Timothy
authors.initials: T
authors.lastname: Littlewood
authors.forename: Graeme M
authors.initials: GM
authors.lastname: Smith
authors.forename: Dominic
authors.initials: D
authors.lastname: Culligan
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chopra
authors.forename: Andrew
authors.initials: A
authors.lastname: Davies
authors.forename: Keiren
authors.initials: K
authors.lastname: Towlson
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Williams
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D016572:Cyclosporine / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage; D003625:Data Collection; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006082:Graft Enhancement, Immunologic / Q000009:adverse effects; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017710:Lymphocyte Transfusion / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D012074:Remission Induction; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007166:Immunosuppressive Agents; D003561:Cytarabine; D000074323:Alemtuzumab; D005047:Etoposide; D016572:Cyclosporine; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan; D002330:Carmustine