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Summary: Background: Follicular lymphoma is the most common form of lymphoma in Europe and the USA. In this prospective, single-arm, open-labelled, multicentre non-randomised phase II trial (FLUMIZ [FLUdarabine, MItoxantrone, Zevalin] trial) we aimed to assess the efficacy and safety of fludarabine and mitoxantrone plus radioimmunotherapy in untreated patients with follicular non-Hodgkin lymphoma (NHL). Methods: Patients with stage III or IV untreated indolent follicular NHL were enrolled between June 1, 2004, and April 15, 2006, at 13 Italian institutions, and were treated with oral fludarabine (40 mg/m2 on days 1 to 3) and intravenous mitoxantrone (10 mg/m2 on day 1) every 28 days for six cycles. Patients who had at least a partial response (PR) with normal platelet counts (>100×109/L) and granulocyte counts (1·5×109/L), and bone-marrow infiltration less than 25% 4–6 weeks after completion of the sixth cycle of chemotherapy were deemed eligible for consolidation treatment 6–10 weeks after the sixth cycle with one course of yttrium-90 (90Y)-labelled ibritumomab tiuxetan (Zevalin), which consisted of an initial infusion of intravenous rituximab (250 mg/m2) on day 1 followed by a second 250 mg/m2 infusion on day 7, 8, or 9. The second infusion was followed by a weight-based dose of 90Y-ibritumomab tiuxetan, administered as a slow intravenous push over 10 min. Primary endpoints were complete response (CR) and haematological toxic effects and secondary endpoints were overall survival and progression-free survival. Responses were classified according to the International Workshop for Response Criteria for non-Hodgkin''s lymphomas. Analysis was per protocol. This trial is registered as a European Standard Controlled Trial on the EudraCT website http://oss-sper-clin.agenziafarmaco.it, number 2004-002211-92. Findings: 61 patients were enrolled in the trial and received six cycles of fludarabine and mitoxantrone, after which an overall response was noted in 98% (60 of 61) of patients (43 of 61 patients had CR and 17 of 61 patients had PR). 57 patients (43 with CR and 14 with PR) were deemed eligible for subsequent 90Y-ibritumomab tiuxetan. Of the 14 patients who had PR after the initial treatment, 12 obtained CR after 90Y-ibritumomab tiuxetan. By the end of the entire treatment regimen 55 of 57 patients achieved CR. With a median follow-up of 30 months (range 21–48), 3-year progression-free survival was estimated to be 76% (95% CI 72·3–82·4) and 3-year overall survival 100%. 36 of 57 patients had grade 3 or 4 haematological toxic effects, and blood transfusions were given to 21 of 57 patients. Interpretation: This trial has provided evidence for the feasibility, tolerability, and efficacy of fludarabine and mitoxantrone plus 90Y-ibritumomab tiuxetan in untreated patients with follicular NHL. Funding: Italian Association for Leukaemias, Lymphomas, and Myeloma, Bologna, Italy. [Copyright &y& Elsevier]

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I 3M ) cut-off values by world regions, a cross-validation by holdout method was used and contingency tables (confusion matrices) were generated. The lower third molar maturity indexes, from both left and right side (I 3M L and I 3M R) and the combination of both sides (I 3M L_I 3M R) were calculated. The new cut-off values, that aim to differentiate between a minor and an adult, with more than 74.00% accuracy for all populations were as follows (I 3M L; I 3M R; I 3M L_I 3M R, respectively): Africa = (0.10; 0.10; 0.10), America = (0.10; 0.09; 0.09), Asia = (0.15; 0.17; 0.14), and Europe = (0.09; 0.09; 0.09). The higher sensitivity (Se) was detected for the I 3M L for male African people (91%) and the higher specificity (Sp) of all the parameters (I 3M L; I 3M R; I 3M L_I 3M R) for Europeans both male and female (> 91%). The original cut-off value (0.08) is still useful, especially in discriminating individuals younger than 18 years old which is the goal of the forensic methods used for justice., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)