title: Autologous lymphocytes as vectors to target therapeutic radiation, using indium-114m, in patients with lymphoid cell malignancy.
abstract: Autologous lymphocytes provide a potential vector for the delivery of a cytotoxic agent in patients with lymphoid cell malignancy. This report describes a phase I-II study using autologous lymphocytes to target the radionuclide indium-114m ((114m)In) in patients with refractory chronic lymphocytic leukaemia or small lymphocytic non-Hodgkin's lymphoma. Nineteen patients, the majority of whom had been heavily pretreated with conventional chemotherapy and radiotherapy, received between 69 and 211 MBq (114m)In-labelled autologous lymphocytes. Approximately 80% of the administered activity was localized in the liver and spleen, with around 5% accumulating in the bone marrow. Ten patients (53%) responded (one complete response and nine partial responses). The median duration of response was 7 months. The median survival for the responders was 14 months and for the non-responders was 3 months. The first notable response in every patient was a fall in peripheral lymphocyte count. The indium treatment was not associated with any subjective toxicity, although all patients suffered from myelosuppression, with thrombocytopenia being the dose-limiting factor. This study has demonstrated a significant anti-tumour effect in a group of patients with late-stage highly resistant disease.
authors.affiliation: Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester, UK. Richard.cowan@christie-tr.nwest.nhs.uk
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cowan
authors.forename: Brian
authors.initials: B
authors.lastname: Murby
authors.forename: Deborah
authors.initials: D
authors.lastname: Gunton
authors.forename: Susan E
authors.initials: SE
authors.lastname: Owens
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Hoyes
authors.forename: Harbans L
authors.initials: HL
authors.lastname: Sharma
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Smith
authors.forename: James
authors.initials: J
authors.lastname: Chang
authors.forename: Bregje
authors.initials: B
authors.lastname: van Kessel
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Nuttall
authors.forename: Derek
authors.initials: D
authors.lastname: Crowther
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006207:Half-Life; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000532:radiotherapy*; D008099:Liver / Q000528:radiation effects; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D013154:Spleen / Q000528:radiation effects; D014182:Transplantation, Autologous
chemical_list: D007205:Indium Radioisotopes