儿童T系急性淋巴细胞白血病99例治疗分析

Outcome of childhood T-cell acute lymphoblastic leukemia： a report of 99 cases

目的 研究急性淋巴细胞白血病2005（ALL-2005）方案对儿童T系急性淋巴细胞白血病（T-ALL）的有效性及预后相关因素.方法 对2005年5月至2013年8月上海儿童医学中心初发的T-ALL患儿采用ALL-2005方案进行分层治疗,根据危险度不同给予相应强度的化疗.分析早期治疗反应、微量残留白血病（MRD）与预后的相关性,应用Kaplan-Meier法对患儿进行生存分析.结果 99例T-ALL患儿随访至2015年8月31日,中位随访时间为60（24 ～ 109）个月,5年无事件生存率（EFS）和总生存率（OS）分别为65％和69％.本组患儿中年龄≥10岁者43例,占43％;起病时白细胞≥50×109/L者61例,占62％;37例（37％）患儿起病时有纵隔增宽.泼尼松治疗8d反应良好71例（72％）,诱导治疗35 d 94例患儿获完全缓解（95％）.42例（55％）患儿35 d MRD ＜0.01％.诱导治疗55 d时共52例患儿MRD ＜0.01％ （78％）.治疗55 d时MRD≥1％的患儿预后差,5年EFS为40％ （P =0.03）.未证实早期T前体白血病（ETP）免疫表型阳性对预后有显著差异影响.99例T-ALL中6例放弃治疗,10例失访,22例复发,1例第二肿瘤,共20例已死亡（包括11例复发、1例第二肿瘤和4例放弃治疗者）.结论 ALL-2005方案治疗儿童T-ALL疗效较好.诱导55 d MRD结果影响预后.

Objective To explore the incidence,clinical characteristics and prognosis of childhood T-cell acute lymphoblastic leukemia （T-ALL） enrolled in protocol ALL-2005.Method Retrospective reviews of patients diagnosed as having T-ALL were studied in the period between May 2005 and August 2013 in Shanghai Children＇s Medical Center.Predictive values of early treatment responses,including prednisone response,bone marrow morphology on day 35 during induction chemotherapy,and minimal residual disease （MRD） monitored by flow cytometry on day 35 and 55,were analyzed.The Kaplan-Meier method was used to assess the survival rates.Result Ninety-nine evaluable patients aged 1-18 years with newly diagnosed T-ALL were enrolled in protocol ALL-2005.The median follow-up period for patients remaining alive in continuous remission was 60 months （24-109 months）.The 5-year event free survival （EFS） and overall survival （OS） rates for these patients were 65% and 69%,respectively.Forty-three （43%） patients were older than 10 years at diagnosis.A total of 61 patients presented with initial white blood cell count （WBC） ≥ 50 ×109/L.Thirty-seven patients with mediastinal mass were found in this study.Seventy-one patients were defined as prednisone good responders （PGR） on day 8 of prednisone therapy.Ninty-four patients achieved complete remission （CR） on day 35 of induction therapy.MRD negative status （〈0.01%） on day 35 were seen in 55% of the 42 assessed patients.MRD negative status on day 55 was seen in 78% of the 52 assessed patients.Patients with high MRD （〉 1%） on day 55 5-year EFS was 40% were associated with poor prognosis （P =0.03）.Early T-cell precursor （ETP） subtype was not associated with treatment outcome in this study.Six patients abandoned therapy,10 lost to follow-up,22 had relapsed disease,1 was diagnosed as having a second tumor and 20 patients died.Conclusion Overall outcome for T-ALL on protocol ALL-2005 is favorable.MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.