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


Rasche, Mareike; Zimmermann, Martin; Borschel, Lisa; Bourquin, Jean-Pierre; Dworzak, Michael; Klingebiel, Thomas; Lehrnbecher, Thomas; Creutzig, Ursula; Klusmann, Jan-Henning; Reinhardt, Dirk (2018). Successes and challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the AML-BFM trials from 1987 to 2012. Leukemia, 32(10):2167-2177.

Abstract

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. Non-response and relapse rates stayed constant despite intensified first-line therapy (p = 0.08 and p = 0.17). 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.

Abstract

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. Non-response and relapse rates stayed constant despite intensified first-line therapy (p = 0.08 and p = 0.17). 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:October 2018
Deposited On:15 Feb 2019 11:17
Last Modified:15 Feb 2019 12:38
Publisher:Nature Publishing Group
ISSN:0887-6924
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41375-018-0071-7
PubMed ID:29550834

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