Prognostic factors of adult Philadelphia chromosome negative acute lymphoblastic leukemia / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the prognostic factors in adult Philadelphia chromosome negative acute lymphoblastic leukaemia (Ph⁻ ALL).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>