Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents

Inclusion Criteria:

• Newly diagnosed, histological or cytological and immunological proven aggressivemature B-cell Non-Hodgkin lymphoma including Burkitt lymphoma (BL), Burkitt leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), or mature B-cell NHL not furtherclassified according to current WHO classification124. For rare subtypes (e.g.primary mediastinal large B-NHL, PMLBL, double hit lymphoma or high-grade B-celllymphoma with MYC and BCL2 and/or BCL6 rearrangements), consultation of the studycenter is recommended.

• availability of slides/blocks for reference pathology and international pathologypanel (except in cases with immunological and cytomorphological assurance ofdiagnosis)

• age at diagnosis < 18 years

• diagnostics and treatment in one of the participating centers of the trial

• no previous chemotherapy, no previous lymphoma-directed treatment. No application ofsteroids for more than two days during the last month

• adequate hepatic, renal and cardiac function, except if alteration is due tolymphoma infiltration. Please contact the study center in case of unclear cases.

• signed informed consent of patient and/or parents/guardians for treatment accordingto the protocol, participation and transfer of data

• follow-up of at least two years after initial diagnosis is expected

• Certificate of vaccination against hepatitis B or negative serology, defined as

• evidence of immunization with HBs-antigen negative, anti-HBs positive andanti-HBc negative or

• negative hepatitis B serology with HBs-antigen negative, anti-HBs and anti- HBcnegative

Exclusion Criteria:

• patients with insufficient work up not allowing a correct stratification into therisk groups

• B-cell neoplasia as second malignancy

• any other medical, psychiatric or social condition prohibiting treatment accordingto the protocol (e.g. previous malignancy, prior organ transplant, HIV infection orAIDS or severe immunodeficiency, etc.)

• participation within a different trial for treatment of B-cell malignancies and/orconcurrent treatment within any other clinical trial. Exceptions to this are theNHL-BFM Registry 2012 and trials with different endpoints, involving aspects ofsupportive treatment which can run parallel to B-NHL 2013 without influencing theoutcome of this trial e.g. trials on antiemetics, antibiotics, strategies forpsychosocial support etc.

• overt hepatitis B or history of hepatitis B

• hypersensitivity to rituximab or to murine proteins or to any of the otherexcipients of the Investigational Medicinal Product rituximab (MabThera®) or toingredients of other IMPs.

• lack of CD20 expression of the lymphoma cells

• pregnancy and lactation