Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012

Cancer research · Acute myeloid leukemia

Since efficacy of salvage therapy mainly contributed to better outcome in pediatric AML, our analysis indicates that a better allocation of patients, who cannot be cured with conventional chemotherapy, to an early ‘salvage-like’ therapy is necessary.

Overall survival (OS) of pediatric patients with acute myeloid leukemia (AML) increased in recent decades. However, it remained unknown whether advances in first‑line treatment, supportive care, or second‑line therapy mainly contributed to this improvement. Here, we retrospectively analyzed outcome and clinical data of 1940 pediatric AML patients (younger than 18 years of age), enrolled in the population‑based AML‑BFM trials between 1987 and 2012. While 5‑year probability of OS (pOS) increased from 49 ± 3 % (1987‑1992) to 76 ± 4 % (2010‑2012; p < 0.0001), probability of event‑free survival only improved from 41 ± 3 % (1987‑1992) to 50 ± 2 % (1993‑1998; p = 0.02) after introduction of high‑dose cytarabine/mitoxantrone, but remained stable since then. Reduced fatal bleedings and leukostasis translated into fewer early deaths (8.1 % vs. 2.2 %; p = 0.001). Strikingly, pOS after non‑response (13 ± 5 % (1987‑1992) vs. 43 ± 7 % (2005‑2010); p < 0.0001) or relapse (19 ± 4 % vs. 45 ± 4 %; p < 0.0001) improved. After 1999, more relapsed or refractory patients underwent hematopoietic stem cell transplantation (HSCT) with increased pOS after HSCT (29 ± 5 % (1993‑1998) vs. 50 ± 4 % (2005‑2010); p < 0.0001). Since efficacy of salvage therapy mainly contributed to better outcome in pediatric AML, our analysis indicates that a better allocation of patients, who cannot be cured with conventional chemotherapy, to an early ‘salvage‑like’ therapy is necessary.

The study shows that the major gains in survival for pediatric AML in the last decades are driven by improved second‑line therapy, especially the use of HSCT after relapse or refractory disease, rather than by intensified initial chemotherapy. This highlights the need for early identification of patients unsuitable for cure with conventional chemotherapy and timely referral to salvage‑like regimens or transplantation.

Evidence level: Állatkísérletes. Állatmodellben vizsgálták.

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