Long-Term Results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: Insight on the Prognostic Value of DNA Index in the Framework of Berlin-Frankfurt-Muenster-Based Chemotherapy

Sapienza University of Rome, Roma, Latium, Italy
Journal of Clinical Oncology (Impact Factor: 18.43). 01/2008; 26(2):283-9. DOI: 10.1200/JCO.2007.12.3927
Source: PubMed


Between May 1995 and August 2000 the Associazione Italiana di Ematologia Oncologia Pediatrica conducted the ALL-95 study for risk-directed, Berlin-Frankfurt-Muenster (BFM) -oriented therapy of childhood acute lymphoblastic leukemia, aimed at exploring treatment reduction in standard-risk patients (SR) and intensification during continuation therapy in intermediate-risk patients (IR) as randomized questions and treatment intensification in high-risk patients (HR). The prognostic value of DNA index was explored in this setting.
A total of 1,744 patients were enrolled (115, SR; 1,385, IR; and 244, HR). SR patients (DNA index >/= 1.16 and < 1.60; age, 1 to 5 years; and WBC < 20,000, non-T-immunophenotype, with no high-risk features) received a reduced induction therapy (no anthracyclines); IR patients were randomly assigned to receive or not receive vincristine and dexamethasone pulses during maintenance; HR therapy was based on a conventional BFM schedule intensified with three chemotherapy blocks followed by a double reinduction phase.
The event-free survival and overall survival probabilities at 10 years for the entire group were 72.5% (SE, 1.3) and 83.6% (SE, 0.9); 85.0% (SE, 3.4) and 95.5% (SE, 2.0) in SR, 75.1% (SE, 1.5) and 87.5% (SE, 0.9) in IR, and 51.0% (SE, 3.2) and 57.2% (SE, 3.3) in HR patients, respectively. Patients with a favorable DNA index had superior EFS in both IR (83.8% [2.7%] v 73.9% [1.7%]) and in HR (67.8% [9.4%] and 49.6% [3.5%]). Of the six patients with DNA index less than 0.8, only one remained in remission.
Favorable DNA index was associated with a better prognosis in IR and HR patients defined by presenting clinical criteria and treatment with a BFM-oriented chemotherapy.

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    • "Altogether , in children with ALL, clinical parameters of adverse outcome are associated with increased levels of proapoptotic vs. anti-apoptotic genes in bone marrow MNCs. Ploidy has been recently recognized as a prognostic factor in ALL, with hyperdiploidy (DNA index ³ 1.16) being associated with a favorable prognosis (Aricò et al., 2008). In our analysis, BCL-2 mRNA showed a positive correlation with the DNA index, both at diagnosis and at the time of remission following induction therapy, whereas BAX expression was inversely correlated with the DNA index at remission. "
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