Article

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.

Pediatric Hematology Oncology, Ospedale dei Bambini G. Di Cristina, Palermo, Italy.
Journal of Clinical Oncology (Impact Factor: 17.88). 01/2008; 26(2):283-9. DOI: 10.1200/JCO.2007.12.3927
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
59 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Separating out the effects of cancer and treatment between central and peripheral components of the O2 delivery chain should be of interest to clinicians for longitudinal evaluation of potential functional impairment in order to set appropriate individually tailored training/rehabilitation programmes. We propose a non-invasive method (NIRS, near infrared spectroscopy) to be used in routine clinical practice to evaluate a potential impairment of skeletal muscle oxidative capacity during exercise in children previously diagnosed with acute lymphoblastic leukaemia (ALL). The purpose of this study was to evaluate the capacity of skeletal muscle to extract O2 in 10 children diagnosed with ALL, 1 year after the end of malignancy treatment, compared to a control group matched for gender and age (mean±SD = 7.8±1.5 and 7.3±1.4 years, respectively).
    PLoS ONE 06/2014; 9(6):e99282. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: After advances in experimental and clinical testing, minimal residual disease (MRD) assay results are considered a determining factor in treatment of acute lymphoblastic leukemia patients. According to MRD assay results, bone marrow (BM) leukemic burden and the rate of its decline after treatment can be directly evaluated. Detailed knowledge of the leukemic burden in BM can minimize toxicity and treatment complications in patients by tailoring the therapeutic dose based on patients' conditions. In addition, reduction of MRD before allo-HSCT is an important prerequisite for reception of transplant by the patient. In direct examination of MRD by morphological methods (even by a professional hematologist), leukemic cells can be under- or over-estimated due to similarity with hematopoietic precursor cells. As a result, considering the importance of MRD, it is necessary to use other methods including flow cytometry, polymerase chain reaction (PCR) amplification and RQ-PCR to detect MRD. Each of these methods has its own advantages and disadvantages in terms of accuracy and sensitivity. In this review article, different MRD assay methods and their sensitivity, correlation of MRD assay results with clinical symptoms of the patient as well as pitfalls in results of these methods are evaluated. In the final section, recent advances in MRD have been addressed.
    Medical Oncology 11/2014; 31(11):266. · 2.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There are heterogeneous approaches to cranial irradiation therapy (CRT) for T-lineage acute lymphoblastic leukemia (T-ALL). We performed a systematic review of studies that specified a radiation strategy and reported survival for pediatric T-ALL. Our analysis included 62 publications reporting 78 treatment groups (patient n=5844). The average event-free survival (EFS) was higher by 6% per 5 years (p<0.001). Adjusting for year, EFS differed by radiation strategy. Compared to the reference group (CRT for all) which had a year-adjusted EFS of 65% (95% confidence interval, CI: 61% to 69%) the adjusted EFS was significantly worse (rate difference (RD) = -9%, 95% CI: -15% to -2%) among studies that used a risk-directed approach to CRT (p=0.004). The adjusted EFS for the other strategies were not significantly different compared to the reference group: CRT for central nervous system positive patients only (RD = -3%, 95% CI: -14% to 7%, p=0.49); CRT omitted for all patients (RD = 5%, 95% CI: -4% to 15%, p=0.33). CRT may not be necessary with current chemotherapy for T-ALL. These associations, however, are susceptible to bias and caution should be applied in drawing definitive conclusions on the comparative effectiveness of alternative CRT strategies.
    American Journal of Hematology 06/2014; · 3.48 Impact Factor