Gopal Ajay K, Gooley Ted A, Rajendran Joseph G, Pagel John M, Fisher Darrell R, Maloney David G, Appelbaum Frederick R, Cassaday Ryan D, Shields Andrew, Press Oliver W
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Biol Blood Marrow Transplant. 2014 Jun;20(6):770-5. doi: 10.1016/j.bbmt.2014.02.004. Epub 2014 Feb 12.
Myeloablative therapy and autologous stem cell transplantation (ASCT) are 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 and had high-risk, relapsed, or refractory B-NHL. Therapeutic infusions of (131)I-tositumomab were derived from individualized organ-specific absorbed dose estimates delivering ≤ 27 Gy 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 years (range, 60 to 76), 2 (range, 1 to 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 to 1620). Fludarabine was safely escalated to 30 mg/m(2) × 7 days. Engraftment was prompt, there were no early treatment-related deaths, and 2 patients had ≥ grade 4 nonhematologic toxicities. The estimated 3-year overall survival, progression-free survival, and nonrelapse mortality were 54%, 53%, and 7%, respectively (median follow up of 3.9 years). Fludarabine up to 210 mg/m(2) can be safely delivered with myeloablative (131)I-tositumomab and ASCT in older adults with B-NHL.
清髓性疗法和自体干细胞移植（ASCT）在老年B细胞非霍奇金（B-NHL）淋巴瘤患者中未得到充分利用。我们推测，基于临床前数据显示的协同作用，同时使用氟达拉滨可增加清髓剂量的（131）I-托西莫单抗。患者年龄≥60岁，患有高危、复发或难治性B-NHL。（131）I-托西莫单抗的治疗性输注源自个体化的器官特异性吸收剂量估计，向关键器官输送的剂量≤27 Gy。72小时后开始使用氟达拉滨，随后进行ASCT以确定最大耐受剂量。36例患者参与了该试验，中位年龄为65岁（范围60至76岁），接受过2种（范围1至9种）先前治疗方案，33%患有化疗耐药疾病。剂量限制器官包括肺（30例）、肾（4例）和肝（2例），（131）I的中位给药活性为471 mCi（范围260至1620）。氟达拉滨安全地递增至30 mg/m²×7天。造血重建迅速，无早期治疗相关死亡，2例患者出现≥4级非血液学毒性。估计3年总生存率、无进展生存率和非复发死亡率分别为54%、53%和7%（中位随访3.9年）。在老年B-NHL患者中，氟达拉滨剂量高达210 mg/m²可与清髓性（131）I-托西莫单抗和ASCT安全联用。
