Abstract:
In the era of molecular targeted drugs, elderly patients with acute myeloid leukemia (AML) are still very difficult to treat, especially those older than 70 years. The decline in immune function leads to serious infection and disease recurrence. The microtransplant treatment regimen (MST) chemotherapy combined with allogeneic hematopoietic stem cell infusion is a new cell therapy regimen. The aim of this MST study was to improve the survival of elderly patients by graft versus leukemia action and improving T-cell immune function. From May 2012 to July 2020, one hundred and eleven patients aged 70 to 88 years with de novo AML were analyzed retrospectively. After induction chemotherapy, patients whom complete remission (CR) was achieved were given another 2 cycles of postremission therapy. The MST groups were given allogeneic stem cell infusion after each chemotherapy cycle. CR, leukemia-free survival, and overall survival (OS) were compared between groups. Additionally, the immune function and the T cell receptor (TCR) library of T cells were detected and analyzed. The MST group exhibited an encouragingly high CR rate (63.8%), even in high-risk patients (54%), and this rate was significantly higher than that in the chemotherapy alone group. The 1-year OS of MST patients was 57.7%, and it was 55.9% in the high-risk group. It was only 37.3% in the chemotherapy alone group. Higher numbers of naive T cells were found in the MST population than in the chemotherapy alone group. More updated T-cell clones were observed in MST patients by T-cell receptor repertoire analysis with a next-generation sequencing methodology. These results suggest that MST is a safe and practical regimen conducive to longer-term survival in patients of a highly advanced age with AML. Furthermore, it has broad clinical value in the recovery of immune function in elderly patients.
摘要:
在分子靶向药物时代,老年急性髓系白血病(AML)患者仍然很难治疗,尤其是70岁以上的人。免疫功能的下降导致严重的感染和疾病复发。微移植治疗方案(MST)化疗联合异基因造血干细胞输注是一种新的细胞治疗方案。这项MST研究的目的是通过移植物抗白血病作用和改善T细胞免疫功能来改善老年患者的生存率。回顾性分析2012年5月至2020年7月的111例70至88岁的初发AML患者。诱导化疗后,获得完全缓解(CR)的患者再接受2个周期的停药后治疗.MST组在每个化疗周期后给予异基因干细胞输注。CR,无白血病生存,比较两组总生存期(OS)。此外,检测和分析T细胞的免疫功能和T细胞受体(TCR)文库。MST组表现出令人鼓舞的高CR率(63.8%),即使是高危患者(54%),这一比率明显高于单纯化疗组。MST患者的1年OS为57.7%,在高危人群中占55.9%。单独化疗组仅为37.3%。在MST群体中发现的幼稚T细胞数量高于单独化疗组。通过使用下一代测序方法的T细胞受体库分析,在MST患者中观察到了更多更新的T细胞克隆。这些结果表明,MST是一种安全实用的治疗方案,有利于高龄AML患者的长期生存。此外,对老年患者免疫功能的恢复具有广泛的临床价值。