Brammer Jonathan E, Stentz Alexander, Gajewski James, Curtin Peter, Hayes-Lattin Brandon, Kovacsovics Tibor, Leis Jose F, Meyers Gabrielle, Nemecek Eneida, Subbiah Nan, Frires Rachel, Palmbach Gundula, Avraham Galit Perets, Slater Susan, Maziarz Richard T
Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
Center for Hematologic Malignancies, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.
Biol Blood Marrow Transplant. 2015 Jan;21(1):89-96. doi: 10.1016/j.bbmt.2014.09.024. Epub 2014 Oct 16.
The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m(2) IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.
BuFluTBI预处理方案的设计主要目标是降低非复发死亡率（NRM），同时在不符合清髓性预处理条件的患者中最大限度地控制原发性疾病。对于预计标准治疗长期生存率有限的血液系统恶性肿瘤患者，在第-5天给予3.2mg/kg静脉注射白消安的门诊预处理方案，在第-4、-3、-2天给予30mg/m²静脉注射氟达拉滨，并进行200cGy全身照射（TBI），随后接受来自相关或无关供体的干细胞输注。移植物抗宿主病（GVHD）预防措施包括环孢素和霉酚酸酯。2005年至2011年共纳入147例患者；59%为髓系疾病，41%为淋巴系疾病。中位年龄为64岁，中位合并症指数（HCT-CI）评分为3分。中位随访3.2年，1年总生存率（OS）为60%，2年为48%，预计5年OS为37%。1年复发率为29%，2年为33%，1年复发死亡率为13%，2年为20%。1年非复发死亡率为27%，2年为33%。54%的患者在2年内发生II-IV级急性移植物抗宿主病（aGVHD），67%的患者在2年内发生慢性移植物抗宿主病（cGVHD）。多因素分析显示，HCT-CI评分4分或更高、移植前Karnofsky功能状态评分（KPS）低于90、血小板植入延迟超过15天以及II-IV级aGVHD是生存不良的独立预测因素。淋巴系和髓系恶性肿瘤的OS或无进展生存期（PFS）无差异。BuFluTBI是一种有效的非清髓性预处理方案，对髓系和淋巴系疾病均有效，非常适合65岁及以上或HCT-CI为4分或更高的患者使用。
