Department of Hematology, Aerospace Center Hospital, Beijing, China.
Ann Palliat Med. 2021 Nov;10(11):11798-11807. doi: 10.21037/apm-21-3122.
Teniposide, as a more potent inhibitor of topoisomerase II compared with etoposide, shows less damage on hematopoietic stem cells. Few data are available on teniposide in hematopoietic stem cell transplantation (HSCT) for high-risk or refractory recurrent hematopoietic malignant diseases, particularly for acute myeloid leukemia (AML).
A retrospective single arm study was conducted to confirm the feasibility of teniposide (300 mg/m2) -intensified HSCT in the treatment of high-risk or refractory recurrent hematopoietic malignant disease by analysing the outcomes of 32 patients, who received transplantation between January 2016 and December 2018. Univariate and multivariate analyses were performed to evaluate prognostic factors of the endpoints. Statistically significant factors (P<0.05) in multivariate analyses were regarded to be predictive.
All patients achieved myeloid engraftment at a median of 13 days (range, 9-28 days), platelet engraftment at 15.5 days (range, 6-142 days), with a cumulative incidence (CI) of platelet engraftment of 93.75%±0.26%. The CI of grade II-IV acute graft versus host disease (aGVHD) was 43.75%±0.80% and that of grade III-IV aGVHD 12.50%±0.35%. The CI of chronic (c)GVHD was 74.07%±0.82% and that of extensive cGVHD 33.33%±0.87%. The CI of relapse was 35.03%±0.76%. The one-year probability of overall survival (OS) was 62.50%±0.09%, while 2-year OS was 46.90%±0.09%, and those of 1- and 2-year leukemia-free-survival (LFS) were 56.30%±0.09% and 46.90%±0.09%, respectively. Generally, the OS and LFS until the end of our follow up were 43.50%±0.09% and 34.80%±0.11%, respectively. The probability of GVHD-free and relapse-free survival (GRFS) was 24.60%±0.08%. Multivariate analysis indicated that the probability of OS was significantly lower in patients with a disease duration of more than 280 days before receiving HSCT and in those with fewer mononuclear cells. For LFS, other than the above two factors, failure to achieve complete response (CR) before HSCT was another independent risk factor. Similarly, the probability of GRFS was significantly lower in patients with longer disease duration (≥280 days) and those receiving stem cells from female donors.
For patients with high-risk or refractory recurrent hematopoietic malignant disease, teniposide-based conditioning regimens followed by allo-HSCT can be considered as an alternative therapy with encouraging prognoses.
依托泊苷作为拓扑异构酶 II 的更强抑制剂，相较于依托泊苷对造血干细胞的损伤较小。在造血干细胞移植（HSCT）治疗高危或难治性复发性血液恶性疾病中，依托泊苷的数据较少，特别是对于急性髓系白血病（AML）。
采用回顾性单臂研究，分析 2016 年 1 月至 2018 年 12 月期间接受移植的 32 例患者的结果，以确认依托泊苷（300mg/m2）强化 HSCT 治疗高危或难治性复发性血液恶性疾病的可行性。采用单变量和多变量分析评估终点的预后因素。将多变量分析中具有统计学意义的因素（P<0.05）视为预测因素。
所有患者均在中位数为 13 天（范围为 9-28 天）时获得骨髓植入，血小板植入中位数为 15.5 天（范围为 6-142 天），血小板植入累积发生率（CI）为 93.75%±0.26%。Ⅱ-Ⅳ级急性移植物抗宿主病（aGVHD）的 CI 为 43.75%±0.80%，Ⅲ-Ⅳ级 aGVHD 的 CI 为 12.50%±0.35%。慢性（c）GVHD 的 CI 为 74.07%±0.82%，广泛性 cGVHD 的 CI 为 33.33%±0.87%。复发的 CI 为 35.03%±0.76%。总生存（OS）的 1 年概率为 62.50%±0.09%，2 年 OS 为 46.90%±0.09%，1 年和 2 年无白血病生存（LFS）的概率分别为 56.30%±0.09%和 46.90%±0.09%。一般来说，我们随访结束时的 OS 和 LFS 分别为 43.50%±0.09%和 34.80%±0.11%。GVHD 无复发和无复发生存（GRFS）的概率为 24.60%±0.08%。多变量分析表明，HSCT 前疾病持续时间超过 280 天和单核细胞数量较少的患者 OS 概率显著降低。对于 LFS，除上述两个因素外，HSCT 前未达到完全缓解（CR）也是另一个独立的危险因素。同样，疾病持续时间较长（≥280 天）和接受女性供者干细胞的患者 GRFS 概率显著降低。
对于高危或难治性复发性血液恶性疾病患者，依托泊苷为基础的预处理方案联合 allo-HSCT 可作为一种有前途的替代治疗方法。
