Shi Yuan-Yuan, Liu Zeng-Yan, Zhang Gui-Xin, He Yi, Han Ming-Zhe, Feng Si-Zhou, Zhang Rong-Li, Jiang Er-Lie
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Department of Hematology, Binzhou Medical University Hospital, Binzhou, China.
Front Pharmacol. 2023 Feb 3;14:1014306. doi: 10.3389/fphar.2023.1014306. eCollection 2023.
This is a small phase I study examining the safety and efficacy of a cladribine (CLAD)-containing conditioning regimen prior to autologous hematopoietic stem cell transplantion (auto-HSCT) for patients with acute myeloid leukemia (AML). All patients, aged 15-54 years (median 32 years), had favorable/intermediate risk AML (n = 20) or acute promyelocytic leukemia (APL; n = 2) and no evidence of minimal residual disease (MRD) prior to transplantation. Fourteen of the 22 patients received the conditioning regimen as follows: busulfan (Bu) + cyclophosphamide (Cy) + CLAD + cytarabine (Ara-c) or idarubicin. The conditioning regimen of 8 patients was without Cy nor idarubicin to reducing adverse cardiac reaction: the regimen of Bu + CLAD+ Ara-c for 6 patients; and the regimen of Bu + melphalan + CLAD + Ara-c for the other 2 patients. All 22 AML patients received peripheral blood stem cell transplantation. The number of infused mononuclear cells and CD34 cells was 10.00 (2.88-20.97) × 10/kg and 1.89 (1.52-10.44) × 10/kg, respectively. Hematopoietic reconstitution was achieved in all patients, with a median time of 13 (10-34) days for neutrophils and 28 (14-113) days for platelets. Two patients suffered from pulmonary infection, 4 patients suffered from septicemia during the neutropenic stage, and the others suffered from infection or gastrointestinal reaction without exceeding grade 3 after conditioning, which were all alleviated by anti-infection and other supportive treatment. None of the patients died of transplantation-related complications. At a median follow-up of 29.5 (ranging from 4.0 to 60.0) months, three patients relapsed after auto-HSCT at a median time of 6 (ranging from 0.5 to 10.0) months. One patient died due to relapse at 18 months after auto-HSCT. The remaining 21 patients were all alive, including 19 patients with negative MRD. The other 2 patients achieved negative MRD after allogeneic HSCT or chemotherapy. The estimated 2-year survival, relapse, and Leukemia-free survival rates were 94.1 ± 5.7%, 14.7 ± 7.9% and 85.3 ± 7.9%, respectively. A CLAD-combination conditioning regimen is efficient and safe for auto-HSCT, indicating an effective approach for AML treatment.
这是一项小型的I期研究，旨在检验含克拉屈滨（CLAD）的预处理方案在急性髓系白血病（AML）患者自体造血干细胞移植（auto-HSCT）前的安全性和有效性。所有患者年龄在15 - 54岁（中位年龄32岁），患有预后良好/中等风险的AML（n = 20）或急性早幼粒细胞白血病（APL；n = 2），且移植前无微小残留病（MRD）证据。22例患者中的14例接受了如下预处理方案：白消安（Bu）+环磷酰胺（Cy）+CLAD+阿糖胞苷（Ara-c）或伊达比星。8例患者的预处理方案中不含Cy或伊达比星以减少不良心脏反应：6例患者接受Bu + CLAD + Ara-c方案；另外2例患者接受Bu +美法仑+CLAD + Ara-c方案。所有22例AML患者均接受了外周血干细胞移植。输注的单个核细胞和CD34细胞数量分别为10.00（2.88 - 20.97）×10⁸/kg和1.89（1.52 - 10.44）×10⁶/kg。所有患者均实现造血重建，中性粒细胞中位重建时间为13（10 - 34）天，血小板为28（14 - 113）天。2例患者发生肺部感染，4例患者在中性粒细胞减少期发生败血症，其他患者在预处理后出现感染或胃肠道反应，均未超过3级，经抗感染及其他支持治疗后均缓解。无患者死于移植相关并发症。中位随访29.5（4.0至60.0）个月时，3例患者在auto-HSCT后复发，中位复发时间为6（0.5至10.0）个月。1例患者在auto-HSCT后18个月因复发死亡。其余21例患者均存活，其中19例患者MRD阴性。另外2例患者在异基因HSCT或化疗后实现MRD阴性。估计2年生存率、复发率和无白血病生存率分别为94.1±5.7%、14.7±7.9%和85.3±7.9%。含CLAD的联合预处理方案对auto-HSCT有效且安全，表明是AML治疗的一种有效方法。
