Objective: To investigate the potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mitigating the adverse prognosis associated with central nervous system leukemia (CNSL) and to assess the significance of prophylactic intrathecal injection. Methods: A retrospective cohort analysis was conducted involving 30 patients with acute leukemia who had a history of CNSL who underwent allo-HSCT at Peking University People's Hospital between September 2012 and March 2018 (referred to as the CNSL-positive group). In addition, 90 patients with acute leukemia were selected from the same period who underwent allo-HSCT without a history of CNSL (referred to as the CNSL-negative group) and a rigorous 1∶3 matching was performed based on disease type, disease status, and transplantation type to form the control group. The prognosis between the two groups was compared using Kaplan-Meier analysis and the high-risk factors for CNSL relapse post-transplant were identified through Cox proportional-hazards model. Results: The median age of patients in the CNSL-negative group was significantly higher than that of patients in the CNSL-positive group (32 years vs. 24 years, P=0.014). No significant differences were observed in baseline data, including sex, disease type, disease status at transplantation, donor-recipient relationship, and human leukocyte antigen consistency between the two groups. The median follow-up time was 568 days (range: 21-1 852 days). The 4-year cumulative incidence of relapse (71.4%±20.9% vs. 29.3%±11.5%, P=0.005) and the cumulative incidence of CNSL post-transplant (33.6%±9.2% vs. 1.2%±1.2%, P<0.001) were significantly higher in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival rate in the CNSL-positive group was significantly lower than that in the CNSL-negative group (23.1%±17.0% vs. 71.5%±11.6%, P<0.001). However, no significant differences were observed in the 4-year cumulative transplant-related mortality and overall survival rates between the two groups (both P>0.05). Multivariate analysis revealed that a history of CNSL before transplantation (HR=25.050, 95%CI 3.072-204.300, P=0.003) was identified as high-risk factors for CNSL relapse post-transplant. Conversely, haploidentical transplantation was associated with a reduced risk of CNSL relapse post-transplant (HR=0.260, 95%CI 0.073-0.900, P=0.034). Within the CNSL-positive group, seven patients received prophylactic intrathecal therapy after transplantation, and their CNSL relapse rate was significantly lower than that of the 23 patients who did not receive intrathecal therapy after transplantation (0/7 vs. 9/23, P=0.048). Conclusions: Patients with a history of CNSL have a higher risk of relapse and experience poorer leukemia-free survival following transplantation. The use of prophylactic intrathecal injection shows promise in mitigating CNSL relapse rates, although further validation through prospective studies is necessary to substantiate these observations.
目的： 探讨异基因造血干细胞移植（allo-HSCT）能否克服合并中枢神经系统白血病（CNSL）患者的不良预后以及预防性鞘内注射的意义。 方法： 回顾性队列研究。收集2012年9月至2018年3月在北京大学人民医院接受allo-HSCT且移植前合并CNSL病史的30例急性白血病患者（CNSL阳性组）；以疾病类型、患者疾病状态和移植类型为因素按1∶3进行严格匹配，从同期接受allo-HSCT的2 807例急性白血病且移植前无CNSL的患者中选择90例患者作为对照（CNSL阴性组），利用Kaplan-Meier法、竞争分析法比较两组预后结局，以及Cox回归模型筛选移植后CNSL发生的高危因素。 结果： CNSL阴性组中位年龄大于CNSL阳性组（32岁比24岁，P=0.014），两组移植时性别、疾病类型、移植时疾病状态、供受者关系、人类白细胞抗原相合度等基线资料差异无统计学意义。总体随访中位时间为568 d（范围21~1 852 d）。CNSL阳性组移植后4年白血病累积复发率高于CNSL阴性组（71.4%±20.9%比29.3%±11.5%，P=0.005），CNSL的4年累积发生率高于CNSL阴性组（33.6%±9.2%比1.2%±1.2%，P<0.001），4年无白血病生存率显著低于CNSL阴性组（23.1%±17.0%比71.5%±11.6%，P<0.001），差异均有统计学意义，但两组的4年累积移植相关死亡率和总体生存率差异无统计学意义（均P>0.05）。多因素分析提示移植前CNSL病史（HR=25.050，95%CI 3.072~204.300，P=0.003）是移植后CNSL发生的高危因素，单倍体移植与移植后CNSL发生减少相关（HR=0.260，95%CI 0.073~0.900，P=0.034）。CNSL阳性组中7例患者在移植后进行了预防性鞘内注射，CNSL的复发率显著低于移植后未进行鞘内注射的患者（0/7比9/23，P=0.048）。 结论： 合并CNSL患者allo-HSCT后复发率较高、无白血病生存率较差，预防性鞘内注射似乎有助于降低此类患者复发率，但仍需大样本甚至前瞻性研究证实。.