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Onkologie 2. April 2014

Development of treatment and clinical results in childhood AML in Austria (1993–2013)

Background

Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials have been performed in Austria (AML-Berlin-Frankfurt-Münster (BFM) 93, AML-BFM 98, and AML-BFM 2004) in close cooperation with the international BFM study center. Herein, we review the pertinent patient characteristics, therapy, and outcome data.

Patients and methods

From January 1993 to April 2013, 249 children and adolescents (193 protocol patients) diagnosed with AML were enrolled in the three BFM studies. Patients were mainly treated in one of five pediatric hematology/oncology centers distributed over Austria.

Results

Many characteristics and outcome parameters were not statistically different between the three trials. Almost similar proportions of patients were stratified into two risk groups: standard risk (SR) (approximately 37 % overall) and high-risk (HR) (61 %). MLL rearrangements were found in 23 % of patients overall as the most frequent genetic aberration subtype. Complete remission (CR) was achieved by 84–95 % of patients. The most important type of event was leukemic relapse (5-year cumulative incidence 40 ± 8 %, 21 ± 5 %, and 39 ± 6 %; p = 0.058), with a trend to a higher rate specifically in SR patients of study AML-BFM 2004 compared with AML-BFM 98. Importantly, the frequency of death from causes other than relapse sequelae declined over the years (AML-BFM 93: 5/42 12 %, AML-BFM 98: 5/57 9 %, and AML-BFM 2004: 5/94 5 %). Altogether, event-free survival at 5 years varied insignificantly (48 ± 8 %, 61 ± 7 %, and 50 ± 6 %; p = 0.406). Nevertheless, survival (pSU) apparently improved from BFM 93 to subsequent studies, both overall (57 ± 8 %, 75 ± 6 %, and 62 ± 6 %; p = 0.046) and regarding the HR group (5-year-probability of survival (pSU) 40 ± 10 %, 66 ± 8 %, and 52 ± 8 %; p = 0.039).

Conclusion

Treatment of pediatric AML in Austria renders survival rates in the range of international best practice. However, unambiguous statistical comparison of treatment periods is eventually hampered by small numbers and inequalities of recruitment. Hence, only internationally collaborative trials will allow developing treatment further to achieve higher cure rates with fewer events.

Heidrun Boztug, Nora Mühlegger, Evgenia Glogova, Georg Mann, Christian Urban, Bernhard Meister, Klaus Schmitt, Neil Jones, Andishe Attarbaschi, Oskar Haas, Sabine Strehl, Thomas Lion, Ulrike Pötschger, Franz-Martin Fink, Helmut Gadner, Michael Dworzak, memo - Magazine of European Medical Oncology

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