The discrepancies could be assigned to the presence of 'atypical' TCRD gene rearrangements or translocations only detectable by SB, but also to efficient PCR-based detection of rearrangements derived from small subclones, which are difficult to detect with SB. Indications for oligoclonality were observed in 38% and 30% of patients with TCRG and TCRD gene rearrangements, respectively, which is comparable to the frequency of oligoclonality in IGH locus. Based on the combined data it was possible to reduce the broad panel of six TCRD and 12 TCRG primer combinations for MRD studies to two TCRD combinations (V␦2-D␦3 and D␦2-D␦3) and six TCRG combinations (V␥I, V␥II, V␥IV family-specific primers with J␥1.1/2.1 and J␥1.3/2.3 primers) resulting in the detection of 80% and 97% of all TCRD and TCRG gene rearrangements, respectively. Finally, the heteroduplex PCR data indicate that MRD monitoring with TCRG and/or TCRD targets is possible in approximately 80% of childhood precursor-B-ALL patients; ෂ55% of patients even have two TCRG and/or TCRD targets.

qPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale. Deauville categories correspond to certain qPET cut values. Thresholds between normal and abnormal response can be derived from the qPET-distribution without need for follow-up data. In our patients, qPET < 1.3 excludes abnormal response with high sensitivity.

To cite this article: Appel IM, Grimminck B, Geerts J, Stigter R, Cnossen MH, Beishuizen A. Age dependency of coagulation parameters during childhood and puberty. J Thromb Haemost 2012; 10: 2254-63.Summary. Background: Use of age-adjusted reference values is crucial for correct diagnosis and management of thrombotic and hemorrhagic disease in children. They vary with utilized reagents and analyzers. Objectives: We established reference values with the Sysmex CA-1500 System and in parallel with the Behring BCS System using reagents from Siemens Healthcare Diagnostics Products GmbH. Methods: After informed consent, blood samples were obtained from 218 healthy children and 52 healthy adults, grouped as 1-6 months (n = 29), 7-12 months (n = 25), 1-5 years (n = 57), 6-10 years (n = 57), 11-18 years (n = 50) and > 19 years (n = 52). Results: Most coagulation parameters demonstrate good comparability between analyzers with the exception of PT and APTT. Single coagulation factors fibrinogen, factor (F) II, FIX, FXI and XII were significantly decreased in the youngest children; the strongest age dependency was found for coagulation inhibitors Protein C and S, both significantly decreased in infancy and young childhood. We confirmed that high levels of von Willebrand factor are found in the youngest children without increased levels of FVIII followed by decreased von Willebrand levels in the subsequent age group. In children with blood group O a less distinct increase in time was found, compared with individuals with one of the other blood groups. Conclusions: The correlation between the CA-1500 and the BCS system was remarkable. Differences were most pronounced between children < 12 months and older children and adults, confirming the phenomenon of developmental hemostasis. The rationale for age-related changes in the hemostatic system remains unraveled. Our results underline the need for age-specific reference ranges.

In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction increases event-free survival in the subgroups with T-cell lymphoblastic lymphoma and whether therapy duration could be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here we report on the secondary aims of the trial: whether the results of the NHL-BFM90 study could be reproduced and evaluation of disease features and prognostic factors. Three hundred and nineteen patients (66 with precursor B-cell lymphoblastic lymphoma, 233 with T-cell lymphoblastic lymphoma, 12 with mixed phenotype, 8 not classifiable) were enrolled. In induction, 215 patients received prednisone and 104 patients received dexamethasone. The median follow-up was 6.8 years (range, 3.0–10.3). The 5-year event-free survival was 82±2% [12 toxic deaths, 5 secondary malignancies, 43 non-response/relapse (central nervous system n=9; all received prednisone during induction)]. The event-free survival rate was 80±5% for patients with precursor B-cell lymphoblastic lymphoma, 82±3% for those with T-cell lymphoblastic lymphoma, and 100% for patients with a mixed phenotype. During induction, significantly more grade III/IV toxicities were observed in patients receiving dexamethasone, resulting in significant treatment delays. The number of toxic deaths did not differ significantly. The only variable associated with outcome was performance status at diagnosis. The 90% event-free survival rate for patients with T-cell lymphoblastic lymphoma shown in study NHL-BFM90 was not replicated, mainly due to more toxic deaths and central nervous system relapses. Dexamethasone in induction may prevent central nervous system relapse more effectively than prednisone but produces a higher burden of toxicity. (#NCT00275106).