Retrospective analysis of data from 73 patients with childhood acute promyelocytic leukaemia receiving modified chemotherapy: a single-centre study.

PURPOSE

Early death (ED) and treatment-related toxicity emerge as two major barriers for curing paediatric acute promyelocytic leukaemia (APL) patients. This study aims to investigate the effect of idarubicin on controlling hyperleukocytosis in induction therapy and the efficacy and safety of a risk-adapted attenuated consolidation chemotherapy.

METHODS

We summarised the characteristics and long-term outcomes of 73 paediatric APL patients treated at our institution from February 2002 to October 2018, during which treatment protocols evolved over three periods and were defined as protocol A, B and C chronologically. All of the patients received an all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) combination remission induction therapy, with hydroxyurea (group A) or idarubicin (group B and C) to control hyperleukocytosis. Consolidation chemotherapy was modified with risk-adapted attenuated intensity and minimised cumulative doses of anthracyclines for group C (144 mg/m and 288 mg/m of daunorubicin equivalents for standard- and high-risk patients, respectively).

RESULTS

The median initial WBC, platelet count, and fibrinogen were 2.9 × 10/L (range 0.9-158.3 × 10/L), 32 × 10/L (range 4-226 × 10/L), and 160 mg/dL (range 53-549 mg/dL), respectively. High-risk and standard-risk were seen in 20.5% and 79.5% of patients, respectively. Three patients (4.1%) suffered early haemorrhagic death. At the end of induction therapy, 68 (93.2%) patients achieved haematologic complete remission (HCR). At a median follow-up of 91.97 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates for the whole cohort were 95.9 ± 2.3% and 88.7 ± 3.8%, respectively. A comparison of HCR rates and documented instances of toxicity between groups A and B + C showed no significant differences. However, idarubicin significantly reduced the peak WBC count (Z = - 3.292, P = 0.001) and duration of hyperleukocytosis (Z = - 2.827, P = 0.005). Estimated 3-year EFS (91.7 ± 8.0%) and OS (100%) rates for group C were not significantly different from those for group B, whereas the risk of treatment-related infections was significantly reduced (χ = 5.515, P = 0.019).

CONCLUSIONS

Idarubicin (8-10 mg/m/day for 2 days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated.