Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Grasser, N.
Long-term results of the ALL-BFM 2000 trial in Austria
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2016. pp. 111
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- Seidel Markus
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- Abstract:
- Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood and adolescence, accounting for 80% of all leukaemias in children. Since 1979 treatment of ALL in Austria follows the protocols of the Berlin-Frankfurt-Münster (BFM) Study Group. Treatment has been adapted and constantly amended through the assessment of initial risk of relapse, based on clinical and leukaemia-associated parameters on the one hand and through the evaluation of response to treatment, such as prednisone response on day 8, bone marrow evaluation on day 15 and remission status on day 33 on the other hand. Minimal residual disease was primarily introduced as an independent risk factor for patient stratification in the ALL-BFM 2000 trial which was performed in Austria, Germany, Italy and Switzerland. MRD levels were monitored by detecting clone-specific rearrangements in immunoglobulin and T-cell receptor genes as semi-quantitative PCR targets and thereby patients were stratified into 3 subgroups. The aim of this thesis was the evaluation and analysis of the long-term results - hence the calculation of event-free-survival (EFS) and overall survival (OS) rates after 10 years from diagnosis - of 608 participating patients in Austria. Further aims of this thesis were to evaluate the prognostic impact of MRD among the whole study cohort and among different subgroups of patients in order to show whether MRD was able to clearly define groups with a low, intermediate or high risk of relapse among them. In the ALL-BFM 2000 trial, 521 pB-cell ALL patients and 87 T-cell ALL patients were identified and EFS and OS rates after 10 years were as follows: 83±2% and 92±1% in pB-cell ALL patients compared to 79±6% and 82±5% in T-cell ALL patients. By using this PCR-based method of MRD assessment 495 pB-cell ALL patients and 78 T-cell ALL patients were eligible for MRD stratification and thus classified as either low-, intermediate- or high-risk due to their MRD results on day 33 and 78 of treatment. Approximately 30% were considered as MRD low-risk and performed with EFS rates of about 90%, whereas about 60% were MRD intermediate-risk patients with EFS of approximately 80% and the remaining 10% were MRD high-risk patients presenting with EFS rates of 65%. Furthermore, a distinct definition of three risk-groups facing different risks of relapse was possible in various biologically and clinically defined subgroups through the application of MRD. In almost all subgroups a superiority of MRD to traditionally used risk factors was observable, redefining prognostic factors in children and adolescents with ALL. The potential of adjustment of treatment based on patient’s MRD results during the initial course of therapy is one of the main achievements of the ALL-BFM 2000 trial and the main message of this thesis.