Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Biol Blood Marrow Transplant. 2018 Jan;24(1):142-149. doi: 10.1016/j.bbmt.2017.08.040. Epub 2017 Sep 22.
Ex vivo CD34 selection before allogeneic hematopoietic stem cell transplantation (allo-HCT) reduces graft-versus-host disease without increasing relapse but usually requires myeloablative conditioning. We aimed to identify toxicity patterns in older patients and the association with overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of 200 patients who underwent CD34 selection allo-HCT using the ClinicMACS® system between 2006 and 2012. All grade 3 to 5 toxicities by CTCAE v4.0 were collected. Eighty patients aged ≥ 60 years with a median age of 64 (range, 60 to 73) were compared with 120 patients aged < 60 years. Median follow-up in survivors was 48.2 months. OS and NRM were similar between ages ≥ 60 and <60, with 1-year OS 70% versus 78% (P = .07) and 1-year NRM 23% versus 13% (P = .38), respectively. In patients aged ≥ 60 the most common toxicities by day 100 were metabolic, with a cumulative incidence of 88% (95% CI, 78% to 93%), infectious 84% (95% CI, 73% to 90%), hematologic 80% (95% CI, 69% to 87%), oral/gastrointestinal (GI) 48% (95% CI, 36% to 58%), cardiovascular (CV) 35% (95% CI, 25% to 46%), and hepatic 25% (95% CI, 16% to 35%). Patients aged ≥ 60 had a higher risk of neurologic (HR, 2.63 [95% CI, 1.45 to 4.78]; P = .001) and CV (HR, 1.65 [95% CI, 1.04 to 2.63]; P = .03) toxicities but a lower risk of oral/GI (HR, .58 [95% CI, .41 to .83]; P = .003) compared with those aged < 60. CV, hepatic, neurologic, pulmonary, and renal toxicities remained independent risk factors for the risk of death and NRM in separate multivariate models adjusting for age and hematopoietic cell transplantation-specific comorbidity index. Overall, the toxicity of a more intense regimen is potentially balanced by the absence of toxicity related to methotrexate and calcineurin inhibitors in older patients. Prospective study of toxicities after allo-HCT in older patients is essential.
在异基因造血干细胞移植（allo-HCT）前进行体外 CD34 选择可降低移植物抗宿主病（GVHD）而不增加复发，但通常需要骨髓清除性预处理。我们旨在确定老年患者的毒性模式及其与总生存（OS）和非复发死亡率（NRM）的关系。我们对 200 例于 2006 年至 2012 年期间使用 ClinicMACS®系统进行 CD34 选择 allo-HCT 的患者进行了回顾性分析。根据 CTCAE v4.0 收集所有 3 至 5 级毒性。比较了 80 名年龄≥60 岁（中位年龄 64 岁[范围：60 至 73]）的患者与 120 名年龄<60 岁的患者。幸存者的中位随访时间为 48.2 个月。年龄≥60 岁与年龄<60 岁的 OS 和 NRM 相似，1 年 OS 分别为 70%和 78%（P=0.07），1 年 NRM 分别为 23%和 13%（P=0.38）。在年龄≥60 岁的患者中，第 100 天最常见的毒性是代谢毒性，累积发生率为 88%（95%CI：78%至 93%），感染性毒性为 84%（95%CI：73%至 90%），血液学毒性为 80%（95%CI：69%至 87%），口腔/胃肠道（GI）毒性为 48%（95%CI：36%至 58%），心血管（CV）毒性为 35%（95%CI：25%至 46%），肝毒性为 25%（95%CI：16%至 35%）。年龄≥60 岁的患者发生神经毒性（HR：2.63[95%CI：1.45 至 4.78]；P=0.001）和 CV 毒性（HR：1.65[95%CI：1.04 至 2.63]；P=0.03）的风险较高，但发生口腔/GI 毒性（HR：0.58[95%CI：0.41 至 0.83]；P=0.003）的风险较低。与年龄<60 岁的患者相比，CV、肝、神经、肺和肾毒性是调整年龄和造血细胞移植特异性合并症指数后死亡和 NRM 风险的独立危险因素。总的来说，在老年患者中，强化治疗方案的毒性可能被甲氨蝶呤和钙调神经磷酸酶抑制剂相关毒性的缺失所平衡。对老年患者 allo-HCT 后毒性进行前瞻性研究至关重要。
