Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Bone Marrow Transplant. 2023 Jun;58(6):667-672. doi: 10.1038/s41409-023-01947-z. Epub 2023 Mar 13.
Clofarabine (Clo) is an immunosuppressive purine analog that may have better anti-leukemic activity than fludarabine (Flu). The addition of total body irradiation (TBI) to conditioning regimens has been widely investigated. However, the use of single agent Clo in combination with intermediate doses of TBI ranging from 4 to 8 Gy has not been studied yet. This study is a double center, observational, retrospective study of patients with high-risk hematological malignancies diagnosed from 2012 to 2021, treated at the American University of Beirut Medical Center in Beirut (AUBMC), Lebanon, and Saint-Antoine Hospital (SAH) in Paris, France. It aims to identify the outcome of patients with high-risk hematological malignancies who underwent allogeneic stem cell transplant (allo-SCT) and received Clo and TBI (4-8 Gy) before transplant. Data regarding patient baseline characteristics, disease-related factors, and transplant outcomes including graft-versus-host disease (GVHD), Non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), were collected. We identified 24 high-risk patients diagnosed with a hematological malignancy. The median age at transplant was 37 years (range 22-78). At the time of the transplant, only 15 patients (63%) were in complete remission (CR). All patients received Clo/TBI (4-8 Gy). After a median follow-up of 40 months, the cumulative incidences of grade II-III acute GVHD, grade IV acute GVHD, and chronic GVHD were 50%, 4%, and 8%, respectively. NRM at 100 days, and 1 year after transplant was 4% and 25%, respectively. 17% of the patients had a relapse or progression of the disease by the end of the study. The 2-year PFS and OS were 50% and 56%, respectively. The median PFS and OS were 66 and 68 months respectively. As a conclusion, Clo/TBI (4-8 Gy) as a conditioning regimen for allo-SCT in high-risk patients confers disease control with an acceptable toxicity profile.
克拉屈滨(Clo)是一种免疫抑制嘌呤类似物,其抗白血病活性可能优于氟达拉滨(Flu)。全身照射(TBI)联合预处理方案已得到广泛研究。然而,尚未研究使用单药克拉屈滨联合 4 至 8Gy 中等剂量 TBI 的方案。这项研究是一项在黎巴嫩贝鲁特美国大学医学中心(AUBMC)和法国巴黎圣安东尼医院(SAH)进行的、针对 2012 年至 2021 年间诊断为高危血液系统恶性肿瘤的患者的双中心、观察性、回顾性研究。其旨在确定接受 allo-SCT 且在移植前接受 Clo 和 TBI(4-8Gy)的高危血液系统恶性肿瘤患者的结局。收集了患者基线特征、疾病相关因素以及移植结局的数据,包括移植物抗宿主病(GVHD)、非复发死亡率(NRM)、无进展生存期(PFS)和总生存期(OS)。我们共纳入了 24 例高危血液系统恶性肿瘤患者。移植时的中位年龄为 37 岁(范围 22-78 岁)。移植时,仅有 15 例患者(63%)处于完全缓解(CR)。所有患者均接受 Clo/TBI(4-8Gy)。中位随访 40 个月后,Ⅱ-Ⅲ级急性 GVHD、Ⅳ级急性 GVHD 和慢性 GVHD 的累积发生率分别为 50%、4%和 8%。移植后 100 天和 1 年的 NRM 分别为 4%和 25%。研究结束时,17%的患者疾病复发或进展。2 年 PFS 和 OS 分别为 50%和 56%。中位 PFS 和 OS 分别为 66 个月和 68 个月。总之,高危患者接受 Clo/TBI(4-8Gy)预处理方案进行 allo-SCT 可控制疾病,且毒性可接受。