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Osteonecrosis (ON) is a common and debilitating side effect of anti-leukemic treatment in children with acute lymphoblastic leukemia (ALL). However, the impact of leukemia itself on ON development remains elusive. We analyzed 76 children enrolled in the ongoing OPAL trial, who had magnetic resonance imaging (MRI) studies at diagnosis. MRI screening revealed 14 osteonecrotic lesions (5 × hips, 9 × knees) of any grade (I-III) in 7 (9.2%) patients. Six months on, the number of ON per patient increased (1 patient), remained constant (2), and decreased (2). The severity increased from grade I to II in two patients, remained constant (1), completely resolved (2), and decreased from grade III to osteoedema (1). No differences between adolescents initially presenting with/without ON were observed concerning age, pubertal stage, body mass index, leukemia characteristics, and clinical presentation. In MRI screening, a remarkable number of adolescents with ALL present with ON at diagnosis. The course of these ON remains highly unpredictable. [ABSTRACT FROM AUTHOR]

Minimal residual disease ( MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia ( ALL), but bone marrow ( BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration ( n = 50) had a worse 5-year event-free survival than those already negative at first aspiration ( n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment. [ABSTRACT FROM AUTHOR]

Deletions on chromosome 6q are frequently reported in hematological malignancies. However, their biological or prognostic impact has not yet been clarified. This study analyzed loss of heterozygosity (LOH) at chromosome 6q and compared the LOH findings in pediatric precursor T lymphoblastic lymphoma (T-LBL) with the LOH findings in precursor-T lymphoblastic leukemia (T-ALL). For LOH analyses, a set of 25 microsatellite-markers on 6q14-q24 were examined. All patients were treated uniformly according to ALL-BFM-type treatment-strategy. A total of 1671 markers were successfully analyzed from 108 T-LBL patients. LOH was detected in 21 T-LBL patients. There was clear association between LOH at 6q and an increased risk of relapse. In comparison, 3109 markers were successfully analyzed from 127 T-ALL-patients. LOH was detected in 16 patients, but was not associated with increased relapse-rate. The localization of the common LOH regions identified for T-LBL and T-ALL samples did not overlap. Therefore patterns of LOH at 6q and the prognostic impact of LOH differ between T-ALL and T-LBL. These results hint at biologic differences between the two diseases. [ABSTRACT FROM AUTHOR]