费城染色体核型和异基因造血干细胞移植对急性淋巴细胞白血病患者疗效的影响

Effect of Philadelphia Chromosome Karyotype and Allogeneic Hematopoietic Stem Cell Transplantation on Patients with Acute Lymphoblastic Leukemia

目的:探究费城染色体核型(Ph)和异基因造血干细胞移植(allo-HSCT)对急性淋巴细胞白血病(ALL)患者疗效的影响。方法:回顾性分析2012年1月-2020年12月血液科429例ALL患者的资料,根据细胞遗传学核型分析结果将患者分为Ph^(+)组(n=64)、Ph^(-)单体核型(MK)组(n=53)和Ph^(-)非MK组(n=312)。根据治疗方案将患者分为allo-HSCT组(n=236)和non-allo-HSCT组(n=193)。分别分析核型和allo-HSCT对ALL患者近期、远期疗效的影响。结果:在429例ALL患者中,6例(1.40%)在诱导治疗期间死亡,60例(13.99%)无反应,最终达到完全缓解(CR)共363例(84.62%),达到微小残留病灶阴性(MRD^(-))共有287例(66.90%)。Ph^(+)组、Ph^(-)MK组、Ph^(-)非MK组的近期疗效(CR%、CR1%、MRD^(-)%)比较无统计学差异(P>0.05)。60例无反应未达到CR的患者的中位OS为6.9个月(95%CI4.6-8.2个月),363例达到CR的患者的中位随访时间为39.8个月(95%CI:28.6-45.9个月)。Ph^(+)组、Ph^(-)MK组和Ph^(-)非MK组远期疗效[5年累计复发率(CIR%)、无病生存率(DFS%)、总生存率(OS%)]比较无统计学差异(P>0.05)。在429例患者中,共有55.01%(236/429例)的患者行alloHSCT。完成≥2个巩固周期后行allo-HSCT的患者近期疗效(CR%、MRD^(-)%)和远期疗效(CIR%、DFS%、OS%)均优于non-allo-HSCT组(P<0.05)。Ph^(+)组、Ph^(-)MK组和Ph^(-)非MK 3个亚组内,行allo-HSCT法的患者的近期和远期疗效也优于non-allo-HSCT患者。多因素逻辑回归分析结果显示,患者肝、脾、淋巴结肿大为CIR、DFS、OS的危险因素,调整后OR分别为1.23(95%CI:1.08-2.78,P=0.032)、1.21(95%CI:1.03-2.34,P=0.038)、1.25(95%CI:1.08-2.97,P=0.028)。未行allo-HSCT是CIR、DFS、OS的危险因素,调整后OR分别为2.34(95%CI:1.18-5.39,P<0.001)、2.15(95%CI:1.10-4.34,P<0.001)、2.28(95%CI:1.09-4.11,P<0.001)。结论:核型(Ph^(+/-)和MK/NMK)对ALL患者近期和远期疗效似乎没有影响;allo-HSCT影响ALL患者近期和远期疗效,可改善其预后;患者肝/脾/淋巴结肿大及不实行allo-HSCT治疗策略是ALL患者预后不良的危险因素。

Objective:To explore the effect of Philadelphia chromosome karyotype(Ph)and allogeneic hematopoietic stem cell transplantation(allo-HSCT)on the treatment of acute lymphoblastic leukemia(ALL).Methods:The data of429patients with all from January2012to December2020were retrospectively analyzed.According to the results of cytogenetic karyotype analysis,they were divided into Ph^(+) group(n= 64),Ph^(-)monomeric karyotype(MK)group(n= 53)and Ph^(-)NMK group(n= 312). According to the treatment plan,they were divided into allo-HSCT group(n= 236)and non-allo-HSCT group(n= 193). The effects of karyotype and allo-HSCT on the short-term and long-term outcomes of all patients were analyzed. Results:Among the429patients, 6(1.40%)died during induction therapy, 60(13.99%)had no response, 363(84.62%)achieved complete remission(CR)and287(66.90%)achieved minimal residual disease negative(MRD^(-)). There was no significant difference in short-term efficacy(CR%,CR1%,MRD^(-)%)among Ph^(+) group,Ph^(-)MK group and Ph^(-)non-MK group(P> 0.05). The median OS was6.9months(95% CI: 4.6-8.2months)for60unresponsive patients and39.8months(95% CI:28. 6-45.9months)for363CR patients. There was no significant difference in the long-term efficacy[5-year cumulative recurrence rate(CIR%),disease-free survival rate(DFS%)and overall survival rate(OS%)among Ph^(+)group,Ph^(-)MK group and Ph^(-)non-MK group(P> 0.05). Among429patients, 55.01%(236/429)underwent alloHSCT. The short-term efficacy(CR%,MRD^(-)%)and long-term efficacy(CIR%,DFS%,OS%)]of patients with allo-HSCT after more than 2 consolidation cycles were better than those of patients with non-allo-HSCT(P< 0.05). For the three subgroups of Phgroup,PhMK group and Ph^(-)non-MK group,the short-term and long-term efficacy of allo-HSCT patients was better than that of non-allo-HSCT patients. Multivariate logistic regression analysis showed that liver/spleen/lymph node enlargement was a risk factor for CIR,DFS and OS,with adjusted or of1.23(95% CI: 1.08-2.78,P= 0.032), 1. 21(95% CI: 1.03-2.34,P= 0.038)and1.25(95% CI: 1.08-2.97,P= 0.028),respectively. No transplantation was a risk fator for CIR,DFS,OS. The adjusted or were2.34(95% CI: 1.18-5. 39,P< 0.001), 2.15(95% CI: 1.10-4.34,P< 0.001)and2.28(95% CI: 1.09-4. 11,P< 0.001),respectively.Conclusion:Karyotype(Ph^(+/-)and MK/non-MK)seems to have no effect on the short-term and long-term efficacy of all patients;allo-HSCT can affect the short-term and long-term efficacy of all patients and improve their prognosis;liver/spleen/lymph node enlargement and non-implementation of allo-HSCT treatment strategy are the risk factors for poor prognosis of all patients.