Myeloablative I-131-Tositumomab with Escalating Doses of Fludarabine and Autologous Hematopoietic Transplantation for Adults Aged ≥ 60 Years with B-Cell Lymphoma.

Publication Type:

Journal Article


Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Volume 20, Issue 6, p.770-5 (2014)


2014, Biologics Production Core Facility, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Experimental Histopathology Core Facility, Flow Cytometry Core Facility, March 2014, Research Trials Office Core Facility - Biostatistics Service, Scientific Imaging Core Facility, Shared Resources


Myeloablative therapy and autologous stem cell transplant (ASCT) is underutilized in older patients with B-cell non-Hodgkin (B-NHL) lymphoma. We hypothesized that myeloablative doses of (131)I-tositumomab could be augmented by concurrent fludarabine based on preclinical data indicating synergy. Patients were ≥60 years of age, had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of (131)I-tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤27Gy to critical organs. Fludarabine was initiated 72 hours later followed by ASCT to define the maximally tolerated dose. Thirty-six patients with a median age of 65 yrs (range 60-76), 2 (range 1-9) prior regimens, and 33% with chemoresistant disease were treated on this trial. Dose limiting organs included lung (30), kidney (4), and liver (2) with a median administered (131)I activity of 471 mCi (range 260-1620). Fludarabine was safely escalated to 30 mg/m(2) x 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 non-hematologic toxicities. The estimated 3 yr overall survival, progression-free survival, and non-relapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 yrs). Fludarabine up to 210mg/m(2) can be safely delivered with myeloablative (131)I-tositumomab and ASCT in older adults with B-NHL.