Silverman L B, Gelber R D, Young M L, Dalton V K, Barr R D, Sallan S E
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer. 1999 Mar 15;85(6):1395-404. doi: 10.1002/(sici)1097-0142(19990315)85:6<1395::aid-cncr25>3.0.co;2-2.
Although it is widely accepted that failure to achieve complete remission (CR) portends a poor prognosis in childhood acute lymphoblastic leukemia (ALL), there is variability in the precise definition of induction failure and, to the authors' knowledge, few published data exist regarding the outcome of patients who are slow to achieve CR.
Between 1987-1995, 774 children with ALL were treated on 2 consecutive protocols and were evaluable to assess the time required to attain CR. The authors compared presenting characteristics and outcomes of patients based on their remission status after 1 month of induction chemotherapy: CR (n = 656), protracted hypoplasia (low peripheral blood counts and/or hypocellular marrow) (n = 95), and persistent leukemia (M2 or M3 bone marrow and/or evidence of extramedullary leukemia) (n = 23). The median follow-up was 5.2 years.
Presenting features that predicted persistent leukemia included a leukocyte count > 100,000/mm3 and T-cell phenotype. Approximately 91% of patients with persistent leukemia and 100% with protracted hypoplasia eventually achieved CR. The 5-year event free survival (EFS) (95% confidence intervals [95% CI] in parentheses) for patients with persistent leukemia after 1 month was 16% (95% CI, 0%, 31%), which was significantly worse (P < 0.001) than that for those who achieved CR within 1 month (5-year EFS, 82%; 95% CI, 79%, 86%) and that for those with protracted hypoplasia (5-year EFS, 79%; 95% CI, 70%, 87%). For patients with persistent leukemia, there was no significant difference in survival based on bone marrow status (M2 or M3) after 1 month or on the number of induction cycles received before achieving CR.
Patients with persistent leukemia at the end of 1 month of therapy have a dismal prognosis, regardless of when they subsequently achieve CR. More intensive and/or novel therapies should be considered for this subset of patients.
尽管人们普遍认为儿童急性淋巴细胞白血病（ALL）未能实现完全缓解（CR）预示着预后不良，但诱导失败的确切定义存在差异，据作者所知，关于达到CR缓慢的患者的预后，几乎没有公开数据。
1987年至1995年间，774例ALL患儿接受了连续两个方案的治疗，并可评估达到CR所需的时间。作者根据诱导化疗1个月后的缓解状态比较了患者的表现特征和预后：CR（n = 656）、持续性发育不全（外周血计数低和/或骨髓细胞减少）（n = 95）和持续性白血病（M2或M3骨髓和/或髓外白血病证据）（n = 23）。中位随访时间为5.2年。
预测持续性白血病的表现特征包括白细胞计数>100,000/mm3和T细胞表型。大约91%的持续性白血病患者和100%的持续性发育不全患者最终实现了CR。诱导化疗1个月后持续性白血病患者的5年无事件生存率（EFS）（括号内为95%置信区间[95%CI]）为16%（95%CI，0%，31%），明显低于1个月内达到CR的患者（5年EFS，82%；95%CI，79%，86%）和持续性发育不全患者（5年EFS，79%；95%CI，70%，87%）（P < 0.001）。对于持续性白血病患者，1个月后的骨髓状态（M2或M3）或达到CR前接受的诱导周期数对生存率没有显著影响。
治疗1个月结束时仍患有持续性白血病的患者预后不佳，无论他们随后何时实现CR。对于这部分患者，应考虑更强化和/或新颖的治疗方法。
