Can a change in the current standard of care for lymphoblastic lymphoma in children (< 18 years) reduce the rate of disease recurrence involving the CNS?

Lymphoblastic lymphoma (LBL) is a rare form of non-Hodgkin lymphoma that affects lymphocytes, a type of white blood cell. It is very similar to acute lymphoblastic leukemia (ALL), but unlike ALL, it typically affects the lymph nodes and organs rather than the bone marrow. The malignant cells can also spread to the central nervous system (CNS, including the brain and spinal cord). The disease occurs mainly in children and adolescents. Symptoms include fatigue, anemia, increased susceptibility to infections, fever, a tendency to bleed, weight loss, and night sweats. The exact causes of LBL are not fully understood, but genetic and environmental factors play a role. The standard treatment for LBL consists of several phases, similar to that for ALL. In the pre-treatment phase, patients receive a pre-treatment regimen consisting of a glucocorticoid (“cortisone”) and a chemotherapeutic agent: cyclophosphamide. The subsequent induction phase involves intensive combination chemotherapy aimed at achieving remission (freedom from disease). In the following consolidation phase, further combination chemotherapy is administered to destroy any remaining cancer cells. This is usually followed by maintenance therapy. Depending on the specific characteristics of the disease, a further phase of intensified therapy and specialized treatment of certain organs (exacompartment therapy) may also be performed, e.g., in cases of involvement of the nervous system (CNS) and the testicles.

The goal of the LBL2018 study is to investigate the efficacy and safety of various treatment strategies for LBL in a larger number of patients, with a particular focus on determining whether prednisolone or dexamethasone is more effective in treating CNS involvement. These are two different corticosteroid medications; it is known that dexamethasone can penetrate the brain more effectively than prednisolone—which could therefore be more effective in treatment.

First, patients are divided into three risk groups based on specific characteristics of their disease: high-risk group (HR), standard-risk group I/II (SR I/II), and standard-risk group (SR). Based on this classification, patients are assigned—in part at random (randomized)—to different treatment groups, which differ in terms of the use of prednisolone, dexamethasone, or an extracompartmental therapy. In general, however, all patients are treated according to the established standard protocol with the individual treatment phases as described above. No new medications are being tested as part of the study. The study is open-label, meaning that medical staff and patients/parents know which medications are being taken. Treatment as part of the study lasts for up to 24 months, during which the efficacy of the therapy and the occurrence of side effects from the various medications are evaluated. The key factor is whether or when the disease progresses again during therapy. The primary endpoint of the study is event-free survival at 87 months.

Children and adolescents under the age of 18 with newly diagnosed lymphoblastic lymphoma are eligible to participate in the study.