The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation

• Published in: Blood Vol. 100; no. 9; pp. 3108 - 3114
• Main Authors: Marks, David I., Lush, Richard, Cavenagh, Jamie, Milligan, Donald W., Schey, Steven, Parker, Anne, Clark, Fiona J., Hunt, Linda, Yin, John, Fuller, Steven, Vandenberghe, Elisabeth, Marsh, Judith, Littlewood, Timothy, Smith, Graeme M., Culligan, Dominic, Hunter, Ann, Chopra, Rajesh, Davies, Andrew, Towlson, Keiren, Williams, Catherine D.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2002; The Americain Society of Hematology
• Subjects: Adult; Aged; Alemtuzumab; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Busulfan - administration & dosage; Carmustine - administration & dosage; Cyclosporine - therapeutic use; Cytarabine - administration & dosage; Data Collection; Etoposide - administration & dosage; Female; Follow-Up Studies; Graft Enhancement, Immunologic - adverse effects; Graft Survival; Graft vs Host Disease - epidemiology; Graft vs Host Disease - prevention & control; Hematologic and hematopoietic diseases; Hematologic Neoplasms - therapy; Humans; Immunosuppressive Agents - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Transfusion - adverse effects; Male; Medical sciences; Melphalan - administration & dosage; Middle Aged; Peripheral Blood Stem Cell Transplantation; Remission Induction; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation Chimera; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Human; Immunopathology; Transfusion; Stem cell; Treatment efficiency; Hematopoietic cell; Homograft; Graft versus host reaction; Malignant hemopathy; Non myeloablative treatment; Treatment; Donor; Graft; Complication; Clinical trial; Conditioning; Therapeutic protocol; Lymphocyte
• DOI: 10.1182/blood-2002-02-0506
• ISSN: 0006-4971

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.