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

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

doi:10.1007/s12254-014-0135-y

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

Memo. 2014;7(1):63-74. doi: 10.1007/s12254-014-0135-y. Epub 2014 Mar 1.

Authors

Heidrun Boztug¹, Nora Mühlegger¹, Evgenia Glogova¹, Georg Mann¹, Christian Urban², Bernhard Meister³, Klaus Schmitt⁴, Neil Jones⁵, Andishe Attarbaschi¹, Oskar Haas¹, Sabine Strehl¹, Thomas Lion¹, Ulrike Pötschger¹, Franz-Martin Fink^{3

6}, Helmut Gadner¹, Michael Dworzak¹

Affiliations

¹ 1St. Anna Kinderspital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Kinderspitalgasse 6, 1090 Vienna, Austria.
² 2Pediatric Oncology-Hematology, Department of Pediatrics, Medical University of Graz, Graz, Austria.
³ 3Pediatric Oncology-Hematology, Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Department of Pediatric Oncology-Hematology, Landes-Kinderklinik Linz, Linz, Austria.
⁵ 6Pediatric Oncology-Hematology, Department of Pediatrics, Paracelsus Medical University of Salzburg, Salzburg, Austria.
⁶ Department of Pediatrics, Bezirkskrankenhaus St. Johann in Tirol, Tirol, Austria.

Abstract

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.

Keywords: Austria; BFM; MLL; Outcome; Pediatric AML; Prognosis.