Voegeli Michèle, Rondeau Stephanie, Berardi Vilei Simona, Lerch Erika, Wannesson Luciano, Pabst Thomas, Rentschler Jochen, Bargetzi Mario, Jost Lorenz, Ketterer Nicolas, Bischof Delaloye Angelika, Ghielmini Michele
Medizinische Universitätsklinik, Liestal, Switzerland.
SAKK Coordinating Center, Bern, Switzerland.
Hematol Oncol. 2017 Dec;35(4):576-583. doi: 10.1002/hon.2348. Epub 2016 Sep 28.
Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y -Ibritumomab tiuxetan (Y -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity.
一方面，自体干细胞移植（ASCT）的标准预处理方案老年患者往往无法耐受。另一方面，单一高剂量美法仑已被证明作为老年患者移植前预处理方案是安全且有效的。钇-伊布替尼（Y-IT）在移植环境中耐受性良好且可行。因此，我们研究了高剂量美法仑与Y-IT联合作为≥65岁患者的预处理方案。挽救化疗后缓解的复发或难治性CD20阳性淋巴瘤患者可以入组。高剂量治疗包括标准剂量的Y-IT（0.4毫居里/千克体重），随后是逐步递增剂量（100、140、170和200毫克/平方米）的美法仑及ASCT。主要目标是确定最大耐受剂量；次要终点是移植后100天的完全缓解（CR）率和毒性。纳入了20例患者（中位年龄72岁）。在任何剂量水平均未发生剂量限制性毒性（DLT）。13例患者完成了治疗，11例可评估疗效。7例患者未完成治疗，原因分别为动员失败（3例）、疾病进展（2例）、心功能恶化（1例）和3级呼吸困难（1例）。7例患者达到CR/完全缓解/未确认（CRu），2例病情稳定。7例缓解患者中有5例在移植后3年以上仍存活。2例病情稳定的患者长期生存分别为3年和5年。3级或更高等级的非血液学治疗相关不良事件（AE）包括感染（6例），其中2例为发热性中性粒细胞减少，腹泻（3例）、粘膜炎、厌食、病毒性肝炎、低钾血症、脱水和多器官功能衰竭（各1例）。Y-IT与高剂量美法仑联合在老年患者ASCT前是可行的，具有良好的活性且毒性可控。
