[Prognostic analysis of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in complete remission in the era of tyrosine kinase inhibitors]

Objective: To study the clinical results and prognostic factors for allo-HSCT of Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in complete remission (CR) in the era of tyrosine kinase inhibitors (TKI) . Methods: We performed a retrospective analysis of the clinical characteristics of 116 patients with Ph(+)ALL who underwent allo-HSCT while in CR. Results: The study population included 72 men and 44 women. The median patient age was 20 years (4-64 years) . The patients received sibling-identical donor (n=21) , haplo (n=77) , and unrelated donor (n=18) HSCT. The overall survival (OS) rate at 5 years was 73.2% (95% CI 63.8% -80.5% ) . In particular, the 5-year OS can reach 87.5% when the time from diagnosis to transplant is <180 days. The 5-years DFS was 61.4% (95% CI 51.8% -69.7% ) , the 5-year molecular and morphology cumulative relapse incidence was 18.5% (95% CI 12.6% -27.3% ) , and the 5-year TRM was 19.9% (95% CI 13.8% -28.7% ) . A multivariate analysis showed that an age range of 15-39 years (HR=2.730, P=0.044) , time from diagnosis to HSCT ≥ 180 days (HR=4.534, P=0.010) , and Ⅲ-Ⅳgrade aGVHD (HR=7.558, P=0.000) were significantly associated with an inferior overall survival. Limited cGVHD subgroup had better OS (HR=0.300, P=0.034) . Sex, WBC count at diagnosis, type of BCR-ABL fusion genes, somatic gene mutations, CR(1) or >CR(1), MRD negative or positive, conditioning regimen based on TBI or Bu, conditioning intensity, donor source, GVHD prophylactic proposal using cyclosporine or tacrolimus, presence/absence of CMV viremia, and presence/absence of EBV viremia were not significantly different in terms of the OS and DFS. Conclusion: Factors influencing the overall survival of Ph(+) ALL patients who underwent allo-HSCT in CR in the TKI era include age, time form diagnosis to HSCT, and aGVHD severity.

目的： 探讨在酪氨酸激酶抑制剂（TKI）时代Ph染色体阳性急性淋巴细胞白血病（Ph(+)ALL）在完全缓解（CR）状态下行异基因造血干细胞移植（allo-HSCT）的预后和影响因素。 方法： 回顾性分析2012年5月至2017年5月河北燕达陆道培医院收治的116例在CR状态下行allo-HSCT的Ph(+)ALL患者的预后及其影响因素。 结果： 116例患者中男72例，女44例。中位年龄20（4～64）岁。同胞全相合移植21例，亲缘单倍型移植77例，非血缘移植18例。5年总生存（OS）率为73.2％（95％CI 63.8％～80.5％），其中诊断至移植间隔时间<180 d的亚组5年OS率为87.5％。5年无病生存（DFS）率为61.4％（95％CI 51.8％～69.7％）。5年细胞形态及分子学水平复发累积发生率为18.5％（95％CI 12.6％～27.3％）。5年移植相关死亡率（TRM）为19.9％（95％CI 13.8％～28.7％）。多因素分析显示，15～39岁（HR＝2.730，P＝0.044）、诊断至移植间隔时间≥180 d（HR＝4.534，P＝0.010）、发生Ⅲ～Ⅳ度急性移植物抗宿主病（aGVHD）（HR＝7.558，P＝0.000）是影响患者OS的不利因素；发生局限型慢性移植物抗宿主病（cGVHD）是影响患者OS的有利因素（HR＝0.300，P＝0.034）。而性别、起病时WBC（<30×10(9)/L，≥30×10(9)/L）、BCR-ABL融合基因类型、体细胞突变类型、移植前状态（CR(1)，>CR(1)）、移植前微小残留病（MRD）水平（MRD阴性，MRD阳性）、预处理方案（全身照射方案，白消安为基础方案）、预处理方案强度、移植类型、GVHD预防方案（环孢素A，他克莫司）、抗胸腺细胞免疫球蛋白的种类、巨细胞病毒和EB病毒血症的有无对OS的影响无统计学意义。 结论： TKI时代Ph(+)ALL在CR状态下行allo-HSCT时，影响生存的因素有年龄、诊断至移植间隔时间和发生重度aGVHD。.

Keywords: Allogeneic hematopoietic stem cell transplantation; Complete remission; Leukemia, lymphoblastic, acute; Philadelphia chromosome; Tyrosine kinase inhibitor.