Non-Hodgkin’s lymphoma

Classification according to ICCC: II.b, c, d, e (Non-Hodgkin lymphomas)

Definition

Non-Hodgkin’s lymphomas (NHLs) are among the fastest-growing cancers in children. NHLs constitute a diverse group of lymphoproliferative disorders which arise from a malignant transformation of lymphocytes at various stages of their maturation.

Occurrence

NHLs account for 7% of childhood cancers. Incidence rates increase with the age: each year, there are 6 new cases per 1 million children in the age group of 5–9, and 15 new cases per 1 million teenagers in the age group of 15–19. Boys are three times more likely to develop non-Hodgkin’s lymphoma than girls.

Symptoms

Non-Hodgkin’s lymphoma (NHL) develops most frequently in the abdominal region (35% of affected paediatric patients). The disease might develop very fast, manifesting itself as a life-threatening episode. Intra-abdominal organs are usually significantly affected, which leads to rapidly expanding abdomen, bowel obstruction (in case of intestinal infiltration) and kidney failure. Intrathoracic infiltration is present in approximately 25% of children with NHL. Mediastinal lymph nodes and thymus are typically affected, and a large pleural effusion can press on the lungs. NHL symptoms involve strong cough and dyspnoea; compression of superior vena cava leads to a noticeable swelling of face and neck. Only about 13% of children with NHL have infiltrations in the area of head and neck; cervical or supraclavicular lymph nodes are typically affected. Pharyngeal tonsils and neck tonsils are less frequently affected. Children often complain of chronic nasal discharge, frequent nosebleeds, later even an obstruction of nasal airways. Bone marrow is infiltrated in less than 20% of children with NHL, and CNS is affected in less than 5% of patients. Some types of NHL are accompanied with non-specific symptoms (fever, weight loss).

Diagnosis

Basic information is obtained from a clinical examination of the patient, followed by a diagnostic imaging examination (X-ray image of chest, ultrasound examination of peripheral lymph nodes, abdomen and pelvis). Blood count is often normal. An advanced lymphoma with a massive infiltration of bone marrow (approximately 10% of children with NHL) is characterised by anaemia, considerable leucopenia and thrombocytopenia.

Biochemical changes in NHL patients can involve high levels of CRP, hyperuricaemia, and hyperphosphataemia. Blood level of lactic dehydrogenase (LDH) provides important information on the size of tumour mass.

Bone marrow examination and neurological examination (including the cerebrospinal fluid examination) are both essential to confirm the diagnosis of NHL.

The correct diagnosis can be established after histological, cytological, immunohistochemical and molecular-genetic testing of the tumour, the sample of which can be obtained by a biopsy of enlarged lymph nodes or of an infiltrated organ. Examination of bone marrow aspiration or a cytological examination of effusion (if present) can confirm the histological diagnosis.

Classification

Highly malignant forms of NHL are typical for children and adolescents. Burkitt’s lymphomas are most common (50–60%). Lymphoblastic lymphoma (mostly T-cell) account for 30% of cases, and large-cell lymphomas account for the rest of NHLs. Follicular lymphomas are rare among children, accounting for only 1–2% in the overall incidence of NHLs.

Therapy

In the Czech Republic, diagnosis and treatment of children and adolescents with NHLs is concentrated in two specialised centres (Department of Paediatric Haematology and Oncology in Prague, and Department of Paediatric Oncology in Brno). Both centres are members of the BFM Working Group, which unites big haemato-oncological centres in Germany, Austria, Czech Republic, and Switzerland. Intensive combined chemotherapy is the main treatment method. The treatment is differentiated according to the level of risk, based on clinical and laboratory prognostic markers. Radiotherapy is used only rarely; it might be indicated to treat a persisting residue of the tumour.

Treatment outcomes

Intensive combined chemotherapy can cure up to 80% of patients. However, treatment of children with chemorefractory lymphoma (approximately 10% of patients) is still very difficult. Despite an intensive salvage chemotherapy, introduction of immunotherapy, and possibly even the allogeneic transplantation of haematopoietic cells, most of these patients experience early relapse, and finally die of the rapidly advancing lymphoma.

Role of general paediatrician

The general paediatrician plays a crucial role in the diagnostic process, considering the eventuality of non-Hodgkin’s lymphoma, and referring the patient to a haemato-oncological centre. Warning signs involve a rapidly deteriorating condition of the child, notably the extending abdomen, significant dyspnoea, and swelling in the area of head and neck.

In the course of treatment, the general paediatrician cooperates with the centre and follows up the patient. Upon treatment completion, the vaccination of paediatric patients is performed in vaccination clinics.