Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Transplant Cell Ther. 2022 Aug;28(8):501.e1-501.e7. doi: 10.1016/j.jtct.2022.05.021. Epub 2022 May 23.
Conditioning regimens play a major role in determining disease outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of i.v. busulfan (Bu) as part of conditioning chemotherapy has been shown to be effective in controlling disease relapse; however, disease relapse remains a major cause of death following allo-HSCT. This study was conducted to determine the long-term outcomes of vorinostat with i.v. Bu plus dual nucleoside analogs clofarabine (Clo) and fludarabine (Flu) in the conditioning regimen for patients undergoing allo-HSCT. This was a rapid dose escalation phase I/II study designed to determine whether the addition of vorinostat would improve the efficacy of standard i.v. Bu/Flu/Clo conditioning regimen. This report presents the long-term disease outcomes of this combination in 68 patients with high-risk leukemia, including 31 (46%) with acute lymphoblastic leukemia (ALL) and 37 (54%) with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Fifty-eight patients (85%) were in morphologic complete remission at time of transplantation, and 38 (56%) received a matched unrelated donor graft. Over the median follow-up of 37.6 months, 29 of the 68 patients died (43%), and the nonrelapse mortality (NRM) rate was 22% (n = 15). The median overall survival and median NRM were not reached. Nineteen patients (28%) experienced disease progression. The median progression-free survival was 36.8 months. Thirty-seven patients (57%) developed grade II-IV acute graft-versus-host disease (GVHD), and 20 patients (31%) developed chronic GVHD. Our results suggest a lack of benefit from adding a short course of vorinostat to i.v. Bu/Flu/Clo conditioning regimens for leukemia patients undergoing allo- HSCT.
预处理方案在异基因造血干细胞移植（allo-HSCT）后决定疾病结局方面发挥着重要作用。静脉注射白消安（Bu）作为预处理化疗的一部分已被证明可有效控制疾病复发；然而，疾病复发仍然是 allo-HSCT 后死亡的主要原因。本研究旨在确定伏立诺他联合静脉注射 Bu 加双核苷类似物克拉屈滨（Clo）和氟达拉滨（Flu）在 allo-HSCT 患者预处理方案中的长期疗效。这是一项快速剂量递增的 I/II 期研究，旨在确定添加伏立诺他是否会提高标准静脉注射 Bu/Flu/Clo 预处理方案的疗效。本报告介绍了该联合方案在 68 例高危白血病患者中的长期疾病结局，其中 31 例（46%）为急性淋巴细胞白血病（ALL），37 例（54%）为急性髓系白血病（AML）或骨髓增生异常综合征（MDS）。58 例（85%）患者在移植时处于形态学完全缓解状态，38 例（56%）接受了匹配的无关供体移植。在中位数为 37.6 个月的随访中，68 例患者中有 29 例（43%）死亡，非复发死亡率（NRM）为 22%（n=15）。中位总生存期和中位 NRM 尚未达到。19 例（28%）患者发生疾病进展。无进展生存期的中位数为 36.8 个月。37 例（57%）患者发生 II-IV 级急性移植物抗宿主病（GVHD），20 例（31%）患者发生慢性 GVHD。我们的结果表明，在接受 allo-HSCT 的白血病患者中，静脉注射 Bu/Flu/Clo 预处理方案中添加短疗程伏立诺他没有获益。
