Tao Shan-Dong, Song Li-Xiao, Deng Yuan, Chen Yue, Zhang Xin, Ding Bang-He, Wang Chun-Ling, Yu Liang
Department of Hematology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Department of Hematology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):677-684. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.010.
To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).
CLAE regimen [cladribine 5 mg/(m·d), d 1-5; cytarabine 1.5 g/(m·d), d 1-5; etoposide 100 mg/(m·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.
2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by and mutations in kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.
CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.
观察克拉屈滨联合阿糖胞苷强化化疗后行异基因造血干细胞移植（allo-HSCT）治疗复发/难治性急性白血病（R/R AL）患者的疗效及安全性。
采用克拉屈滨联合阿糖胞苷方案[克拉屈滨5 mg/(m²·d)，第1 - 5天；阿糖胞苷1.5 g/(m²·d)，第1 - 5天；依托泊苷100 mg/(m²·d)，第3 - 5天]后行allo-HSCT治疗3例R/R AL患者。患者在复发或难治状态下接受克拉屈滨联合阿糖胞苷化疗，并进行骨髓穿刺以判断骨髓发育异常状态。间隔3至5天后，进行allo-HSCT预处理方案[氟达拉滨30 mg/(m²·d)，第 -7至 -3天；白消安0.8 mg/kg，每6小时1次，第 -6至 -3天或第 -5至 -2天。若骨髓增生不活跃且原始细胞小于10%，白消安使用3天。若骨髓增生活跃且原始细胞大于10%，白消安使用4天]。使用环孢素A、霉酚酸酯和短期甲氨蝶呤预防移植物抗宿主病（GVHD）。移植后，对所有3例患者定期监测微小残留病（MRD）状态和骨髓嵌合情况，并在移植后3个月使用去甲基化药物或达沙替尼预防复发。
2例t(11;19)易位及复发/难治性急性髓系白血病患者在诱导缓解后6个月内复发，分别接受克拉屈滨联合阿糖胞苷方案强化化疗后行单倍体allo-HSCT和无关供者allo-HSCT。2例患者均在移植后6个月复发，随后通过供者淋巴细胞输注、干扰素、白细胞介素-2等方法达到完全缓解，移植后无病生存期为2年。另1例患者为慢性髓性白血病，在口服酪氨酸激酶抑制剂期间发生急性淋巴细胞白血病，伴有激酶区域和其他染色体异常的 和 突变。诱导化疗达到形态学缓解后并发中枢神经系统白血病。在MRD阳性状态下，采用克拉屈滨联合阿糖胞苷方案强化化疗后行同胞allo-HSCT。患者在移植后3个月复发，嵌合抗原受体T细胞（CAR-T）治疗后达到缓解，然而，他在移植后5个月因严重细胞因子释放综合征（CRS）和GVHD死亡。
克拉屈滨联合阿糖胞苷方案后行allo-HSCT可能是R/R AL患者延长总生存期的有效挽救治疗选择。
