Objective: To analyze the prognostic factors in adult Philadelphia chromosome negative acute lymphoblastic leukaemia (Ph⁻ ALL).
Methods: From December 1999 to December 2013, 353 consecutive hospitalized 18-65-year-old adult Ph⁻ ALL patients were retrospectively analyzed. Induction therapy was CODP±L-asparaginase (L-Asp) regimen, and consolidation therapy included CODP and high dose methotrexate or revised Hyper-CVAD A and B regimens for 8 cycles. 178 patients (50.4%) performed allo-HSCT after three to five cycles of consolidation treatment, and 172 patients didn't receive allo-HSCT. The median follow-up was 39.9 months (2.0 to 171.0 months) for the 184 survivors.
Results: Three patients (0.85%) happened early death. CR rate after the first cycle of induction chemotherapy was 77.4% (271/350) among evaluated 350 patients. Overall CR rate was 92.9% (325/350). WBC ≥ 100.0 × 10⁹/L (P=0.010) and hepatomegaly/splenomegaly/lymphadenopathy (P=0.036) were independent adverse factors for overall CR. Among the 325 CR patients, 117 patients developed relapse, cumulative incidence of relapse (CIR) at 5 years was 43.2%, disease-free survival (DFS) and overall survival (OS) rates at 5 years were 44.7% and 45.6% respectively. Multivariate analysis showed that harboring central nervous system leukaemia (CNSL) at diagnose (P=0.004, P=0.002, P<0.001, respectively), induction regimen without L-Asp (P=0.023, P=0.009, P=0.004, respectively), time to CR more than 4 weeks (P=0.034, P=0.024, P=0.003, respectively), and non-allo-HSCT (P<0.001, P<0.001, P<0.001, respectively) were adverse factors of relapse, DFS and OS. In addition, high WBC count at diagnosis (≥ 30.0 × 10⁹/L for B lineage and ≥ 100.0 × 10⁹/L for T lineage) was poor factor of DFS (P=0.044). Based on the four adverse prognostic factors of DFS above mentioned (including WBC at diagnose, harboring CNSL at diagnose, induction regimen with or without L-Asp, time to CR more than 4 weeks), patients were grouped into low risk (no factor), intermediate risk (one factor), and high risk (at least two factors). Non-allo-HSCT and allo-HSCT had similar outcomes in low risk subgroup. Allo-HSCT significantly improved OS and DFS in intermediate and high risk subgroups rather than non-allo-HSCT (all P values < 0.001).
Conclusion: In adult Ph- ALL patients, high WBC count at diagnosis (≥ 30.0 × 10⁹/L for B lineage and ≥ 100.0 × 10⁹/L for T lineage), CNSL at diagnosis, induction regimen without L-Asp, time to CR more than 4 weeks and non-allo-HSCT were adverse prognostic factors. Allo-HSCT improved OS and DFS in patients with more than one of the first four adverse prognosis factors.
目的: 分析影响成人Ph染色体阴性急性淋巴细胞白血病（Ph−ALL）患者预后的因素。
方法: 回顾性分析1999年12月至2013年12月连续收治的18~65岁Ph−ALL患者353例，以CODP±左旋门冬酰胺酶（L-Asp）方案诱导化疗，采用CODP和大剂量甲氨蝶呤（MTX）交替或改良Hyper-CVAD方案巩固化疗，178例（50.4%）患者在巩固3～5个疗程后行异基因造血干细胞移植（allo-HSCT），172例（49.6%）患者继续接受巩固和维持化疗。存活患者中位随访时间39.9（2.0～171.0）个月。
结果: 3例（0.85%）患者早期死亡。350例可评估患者中，1个疗程完全缓解（CR）271例（77.4%），总CR 325例（92.9%）。WBC≥100.0×109/L（P=0.010）、肝/脾/淋巴结肿大（P=0.036）是影响患者总CR的独立预后因素。在325例CR患者中，117例（36.0%）复发，5年累积复发率（CIR）为43.2%，5年无病生存（DFS）率和总生存（OS）率分别为44.7%和45.6%。多因素分析显示：诊断时伴随中枢神经系统白血病（CNSL）（P值分别为0.004、0.002和<0.001）、诱导治疗未加用L-Asp（P值分别为0.023、0.009、0.004）、4周诱导化疗后未达CR（P值分别为0.034、0.024、0.003）以及未进行allo-HSCT（P值均<0.001）是影响患者复发、DFS及OS率的独立预后不良因素；诊断时高WBC（B-ALL≥30×109/L，T-ALL≥100×109/L）（P=0.044）是降低DFS率的独立因素。以影响CR患者DFS的四个预后因素（诊断时WBC、是否伴随CNSL、诱导治疗是否加用L-Asp及4周诱导化疗后是否达CR）将患者分为低危组（无不良因素）、中危组（1个不良因素）和高危组（至少2个不良因素）。低危组非allo-HSCT和allo-HSCT患者DFS和OS差异无统计学意义，中、高危组中，相对于非allo-HSCT，allo-HSCT显著改善患者DFS和OS（P值均<0.001）。
结论: 对于成人Ph−ALL患者，诊断时WBC偏高（B-ALL≥30×109/L，T-ALL≥100×109/L）、诊断时伴随CNSL、诱导治疗未加用L-Asp、诱导治疗4周未达CR及非allo-HSCT是独立影响预后的不良因素，具有前四项中一个或一个以上不良预后因素的患者，采用allo-HSCT更具生存优势。