Non-Hodgkin lymphoma in children: A 20-year population-based epidemiologicstudy in western Sweden

Purpose: The aim of this study was to investigate incidence, clinicopatholo gic features, prognostic risk factors, and long-term survival in non-Hodgki n lymphoma (NHL) in a 20-year population-based study of children using Swed ish health care organizations and their central registry for childhood mali gnancies. Patients and Methods: The hospital registry, the Cause of Death Registry, a nd the two established Swedish registries for malignancy (the Swedish Cance r Registry and the National Registry for Solid Tumours in Childhood) were s earched for children in western Sweden with NHL diagnosed from 1975 to 1994 . The clinical files of all children with NHL were collected and abstracted for information regarding age at diagnosis, gender, disease characteristic s, treatment, and outcome of treatment. All sections from paraffin-embedded blocks of tumors with a diagnosis of malignant lymphoma were collected and reexamined histopathologically and immunohistochemically. To guarantee tha t no patients with NHL were misdiagnosed, a reexamination of other childhoo d malignancies collected from these registries was also performed. Median f ollow-up duration of surviving patients is 10 years. Results: The annual incidence of NHL in children younger than 15 years of a ge was 9/million children, representing 6% of all childhood malignancies du ring the investigation time. The male-female ratio was 4.1:1.0. Immunologic marker studies were available for Q-1 of the 77 NHLs: 41 patients had B-ce ll, 17 had T-cell, and 6 had Ki-1-positive anaplastic large cell lymphoma ( ALCL). Two patients with Ki-1-positive ALCL were originally thought to have malignant histiocytosis and Langerhans cell histiocytosis (LCH), respectiv ely. Treatment was the most significant prognostic factor; event-free survi val (EFS) was 19% in the preprotocol era (1975 to 1979) and 74% from 1980 t o 1994. Other than treatment, stage was the most significant prognostic fac tor; EFS was 86% for patients (1980 to 1994) with stage I or II disease and 64% for patients with stage III or IV disease, with a dismal prognosis for children with initial involvement of the bone marrow or central nervous sy stem (EFS was 38% and 20%, respectively). Bulky disease and performance sta te at diagnosis were independent prognostic factors. The patterns of relaps e, including early recurrence of the B-cell lymphomas, are in accordance wi th previous experience. Conclusion: The incidence of NHL was found to be somewhat higher than repor ted in our previous Nordic study. The higher incidence found in this study might be the result of the thorough data collection (based on hospital regi stry and cross-checked with all registries for malignant diseases in Sweden ) or because reexamination of the tissue material was performed. A more pro nounced male predominance than found in previous investigations was observe d. The immunophenotypic distribution and the stage distribution is in accor dance with earlier investigations. Treatment was the most important factor affecting outcome. A dramatic improvement of survival was seen with the int roduction of intensive therapy; treatment success can be expected in 86% of children with localized disease and 64% of children with extensive disease . The absence of improvement in survival despite further treatment stratifi cation with the introduction of the BFM protocol for B-cell-NHL is surprisi ng. LSA2L2-like protocols seem to be as effective. Future studies on treatm ent of NHL must also concentrate on reducing the intensity of therapy in pa tients with lower risk disease to minimize late toxic effects.