title: Phase 1/2 trial of total marrow and lymph node irradiation to augment reduced-intensity transplantation for advanced hematologic malignancies.
abstract: This phase 1/2 study assessed the augmentation of reduced-intensity conditioning (RIC) with total marrow and lymph node irradiation (TMLI), for peripheral blood stem cell transplantation, in patients with advanced hematologic disease. The regimen consisted of fludarabine 25 mg/m(2) per day for 5 days, melphalan 140 mg/m(2) for one day, and TMLI radiation at 150 cGy/fraction in 8 fractions over 4 days. Eligible patients were over 50 years old and/or had compromised organ function. Median age of the 33 evaluable patients was 55.2 years. Eighteen events of nonhematologic grade III or higher toxicities occurred in 9 patients. Day 30 and day 100 mortalities were 3% and 15%, respectively. Patients achieved myeloid and platelet engraftment at a median of 14 days after transplantation. Long-term toxicities occurred in 2 patients: hypokalemia and tremor, both grade III, on days 370 and 361 after transplantation. Fourteen patients died, 7 of relapse-related causes and 7 of non-relapse-related causes. With a median follow-up for living patients of 14.7 months, 1-year overall survival, event-free survival, and non-relapse-related mortality were 75%, 65%, and 19%, respectively. Addition of TMLI to RIC is feasible and safe and could be offered to patients with advanced hematologic malignancies who might not otherwise be candidates for RIC.
authors.affiliation: Department of Hematology/Hematopoietic Stem Cell Transplantation, City of Hope, Duarte, CA 91010, USA. jrosenthal@coh.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenthal
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wong
authors.forename: Anthony
authors.initials: A
authors.lastname: Stein
authors.forename: Dajun
authors.initials: D
authors.lastname: Qian
authors.forename: Debbie
authors.initials: D
authors.lastname: Hitt
authors.forename: Hossameldin
authors.initials: H
authors.lastname: Naeem
authors.forename: Andrew
authors.initials: A
authors.lastname: Dagis
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Thomas
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D002648:Child; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D010865:Pilot Projects; D011446:Prospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan