Minimal residual disease before and after transplantation for childhood acute lymphoblastic leukaemia: is there any room for intervention?

作者：Balduzzi Adriana^*; Di Maio Lucia; Silvestri Daniela; Songia Simona; Bonanomi Sonia; Rovelli Attilio; Conter Valentino; Biondi Andrea; Cazzaniga Giovanni; Valsecchi Maria G

来源：British Journal of Haematology, 2014, 164(3): 396-408.

DOI：10.1111/bjh.12639

• acute lymphoblastic leukaemia
• childhood
• minimal residual disease
• allogeneic transplantation
• relapse

Eighty-two children and adolescents who underwent allogeneic transplantation for acute lymphoblastic leukaemia in remission (period 2001-2011, median follow-up 49years) had been assessed for minimal residual disease (MRD) by real-time quantitative polymerase chain reaction before and at 1, 3, 6, 9 and 12months after transplantation. Five-year event-free survival (EFS) and cumulative incidence of relapse were 777% [standard error (SE) 57] and 114% (SE 44), respectively, for patients with pre-transplant MRD <1x10(-4) (68%), versus 308% (SE 91; P<0001) and 615% (SE 95; P<0001), respectively, for those with MRD 1x10(-4) (32%). Pre-transplant MRD 1x10(-4) was associated with a 92-fold risk of relapse [95% confidence interval (CI) 354-2388; P<0001] compared with patients with MRD <1x10(-4). Patients who received additional chemotherapy pre-transplant to reduce MRD had a fivefold reduction of risk of failure (hazard ratio 019, CI 005-070, P=001). Patients who experienced MRD positivity post-transplant did not necessarily relapse (5-year EFS 403%, SE 93), but had a 25-fold risk of failure (CI 105-575; P=004) if any MRD was detected in the first 100d, which increased to 78-fold (CI 22-2778; P=0002) if detected after 6months. Anticipated immunosuppression-tapering according to MRD may have improved outcome, nevertheless all patients with post-transplant MRD 1x10(-3) ultimately relapsed, regardless of immunosuppression discontinuation or donor-lymphocyte-infusion. In conclusion, MRD before transplantation had the strongest impact on relapse and MRD positivity after transplantation, mostly if detected early and at low levels, did not necessarily imply relapse. Additional intensified chemotherapy and modulation of immunosuppression may reduce relapse risk and improve ultimate outcome.

• 出版日期2014-2