Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan; Department of Oncology, Blood and Marrow Stem Cell Transplant Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
Department of Oncology, Blood and Marrow Stem Cell Transplant Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
Transplant Cell Ther. 2021 Aug;27(8):665.e1-665.e7. doi: 10.1016/j.jtct.2021.04.029. Epub 2021 May 12.
Fludarabine 30 mg/m/d × 5 and melphalan 140 mg/m × 1 (Flu-Mel140) is a commonly used reduced-intensity conditioning regimen. We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes. Primary objectives was overall survival (OS) at 3 years. Secondary objectives were to assess the cumulative incidences of acute and chronic GVHD, relapse-free survival (RFS), relapse rate, and nonrelapse mortality (NRM). We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell transplantation (alloSCT) using peripheral blood stem cells. Eighty-one patients (median age, 58 years) underwent alloSCT between January 2008 and December 2018. Thirty-one percent of patients had a prior transplant, 32% had high or very-high disease risk index, and the donor was unrelated in 70% of patients. Grade 3 to 4 regimen-related toxicities were mucositis (37%), cardiac toxicity (17%), and renal toxicity (10%). The cumulative incidence of grade III to IV acute GVHD at day +100 was 24.7% and chronic GVHD at 1 year was 51.3%. Median follow-up for survival was 6.1 years. At 3 years, OS was 39.81%, RFS was 31.47%, and relapse rate was 30.5%. One-year NRM was 29.9%. Patients undergoing first transplantation experienced improved OS compared with second or beyond (63.08% versus 42.31%, P = .02). After adjusting for disease subtypes, age (≤55 versus 55), comorbidity index (CI), number of transplant and GVHD prophylaxis, multivariable analysis did not demonstrate any survival difference among disease subtypes. High CI (≥3) was predictive of adverse OS and NRM, whereas older age (>55 years) was associated with high NRM. Our study shows that Flu-Mel140-TBI seems feasible and provides durable disease control. Addition of TBI did not appear to improve outcomes compared to previously published reports of Flu-Mel140. Considerable NRM could result from the inclusion of patients with older age and prior transplants.
氟达拉滨 30mg/m/d×5 和马法兰 140mg/m×1（Flu-Mel140）是一种常用的减低强度预处理方案。我们假设在 Flu-Mel140 中加入 200cGy 全身照射（TBI）可能会提高抗肿瘤活性和移植结果。主要目标是 3 年的总生存（OS）。次要目标是评估急性和慢性移植物抗宿主病（GVHD）、无复发生存（RFS）、复发率和非复发死亡率（NRM）的累积发生率。我们回顾性评估了 81 例接受 Flu-Mel140-TBI 后继以 HLA 匹配供体异基因造血干细胞移植（alloSCT）的患者的结果，这些患者使用外周血干细胞。81 例患者（中位年龄 58 岁）于 2008 年 1 月至 2018 年 12 月期间接受 alloSCT。31%的患者有既往移植史，32%的患者有高或极高疾病风险指数，70%的患者供者为无关供者。3 级至 4 级方案相关毒性为黏膜炎（37%）、心脏毒性（17%）和肾毒性（10%）。第 100 天的 3 级至 4 级急性 GVHD 的累积发生率为 24.7%，1 年慢性 GVHD 的发生率为 51.3%。生存随访中位数为 6.1 年。3 年时，OS 为 39.81%，RFS 为 31.47%，复发率为 30.5%。1 年 NRM 为 29.9%。与第二次或以后的移植相比，第一次移植的患者 OS 改善（63.08%比 42.31%，P=0.02）。在调整疾病亚型、年龄（≤55 岁与＞55 岁）、合并症指数（CI）、移植和 GVHD 预防次数后，多变量分析显示疾病亚型之间的生存无差异。高 CI（≥3）预示 OS 和 NRM 不良，而年龄＞55 岁与高 NRM 相关。我们的研究表明，Flu-Mel140-TBI 似乎是可行的，并能提供持久的疾病控制。与 Flu-Mel140 的先前报告相比，加入 TBI 似乎并没有改善结果。由于包括年龄较大和既往移植的患者，相当高的 NRM 可能导致。
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