Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Transplant Cell Ther. 2022 Jun;28(6):326.e1-326.e10. doi: 10.1016/j.jtct.2022.03.017. Epub 2022 Mar 17.
Even in the era of high-intensity chemotherapy, disease recurrence remains a major cause of treatment failure in adult patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative B-ALL). For patients who achieved second complete remission (CR2) with salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be the best curative treatment. However, limited data are available on the outcomes of allo-HSCT for adult Ph-negative B-ALL in CR2 in the high-intensity chemotherapy era. We evaluated the transplantation outcomes of adult patients with Ph-negative B-ALL in CR2 compared with those in CR1. We also clarified the prognostic factors among adult allo-HSCT recipients with Ph-negative B-ALL in CR2. We conducted a nationwide retrospective study using the data form Japanese transplant registry database. Patients aged ≥16 years and underwent their first allo-HSCT between 2003 and 2017 were included. The 3-year overall survival (OS) rate of the patients in CR2 (n = 382) was significantly lower than that in first complete remission (n = 1375) (51.8% versus 68.1%; P < .001), accompanied by a higher relapse rate (34.2% versus 17.6% at 3 years; P < .001). In a multivariate analysis among CR2 patients, time from diagnosis to allo-HSCT (≤2 years) was a significant factor for OS (hazard ratio [HR] 1.87; P < .001) and relapse (HR = 1.88; P < .001), whereas age at allo-HSCT (≥30 years) was a significant factor for OS (HR = 2.10, P < .001) and nonrelapse mortality (HR = 2.68; P < .001). By assigning a score of 1 to each factor, the 3-year OS rate of CR2 patients significantly stratified: 70.7% in patients with score 0, 56.4% with score 1, and 28.4% with score 2 (P < .001). The survival outcomes of allo-HSCT in adult Ph-negative B-ALL patients in CR2 were inferior to those in CR1 in the high-intensity chemotherapy era, mainly because of the higher relapse rate. Among the CR2 patients, the short time between diagnosis and allo-HSCT was a significant risk factor for disease recurrence and overall mortality. Better disease control with novel treatment strategies may be needed for early relapse. In addition, the nonrelapse mortality rate in patients over 30 years of age was particularly high among CR2 patients, suggesting the need for improved supportive care for these patients. Further studies are warranted on the outcomes of allo-HSCT after achieving CR2 with novel drugs, such as inotuzumab ozogamicin and blinatumomab.
即使在高强度化疗时代，疾病复发仍然是导致成人费城染色体阴性 B 细胞急性淋巴细胞白血病（Ph-阴性 B-ALL）治疗失败的主要原因。对于接受挽救性化疗后达到第二次完全缓解（CR2）的患者，异体造血干细胞移植（allo-HSCT）可能是最佳的治愈性治疗方法。然而，在高强度化疗时代，关于 CR2 成人 Ph-阴性 B-ALL 患者接受 allo-HSCT 的结果的数据有限。我们评估了与 CR1 相比，CR2 成人 Ph-阴性 B-ALL 患者的移植结果。我们还阐明了 CR2 成人 allo-HSCT 接受者的预后因素。我们使用日本移植登记数据库中的数据表单进行了一项全国性回顾性研究。纳入年龄≥16 岁且在 2003 年至 2017 年间接受首次 allo-HSCT 的患者。CR2 患者（n=382）的 3 年总生存率（OS）明显低于首次完全缓解患者（n=1375）（51.8% vs. 68.1%；P<.001），且复发率更高（3 年时分别为 34.2%和 17.6%；P<.001）。在 CR2 患者的多变量分析中，诊断至 allo-HSCT 的时间（≤2 年）是 OS（风险比[HR]1.87；P<.001）和复发（HR=1.88；P<.001）的显著因素，而 allo-HSCT 时的年龄（≥30 岁）是 OS（HR=2.10，P<.001）和非复发死亡率（HR=2.68；P<.001）的显著因素。通过为每个因素分配 1 分，CR2 患者的 3 年 OS 率明显分层：0 分患者为 70.7%，1 分患者为 56.4%，2 分患者为 28.4%（P<.001）。在高强度化疗时代，与 CR1 相比，CR2 成人 Ph-阴性 B-ALL 患者 allo-HSCT 的生存结果较差，主要是因为复发率较高。在 CR2 患者中，诊断与 allo-HSCT 之间的时间较短是疾病复发和总死亡率的显著危险因素。可能需要新型治疗策略来更好地控制疾病，以预防早期复发。此外，CR2 患者中年龄>30 岁的患者非复发死亡率特别高，这表明需要改善对这些患者的支持性护理。需要进一步研究在新型药物（如 inotuzumab ozogamicin 和 blinatumomab）达到 CR2 后 allo-HSCT 的结果。
