Management of paediatric lymphoma.
The high cure rate obtained in most paediatric lymphomas allows an optimistic vision of future treatments, with decreased primary late effects observed in patients who have completed therapy: decreased cognitive functional impairment, reproductive dysfunction, poor social adaptation, and risk of second malignancies. The deleterious effects of radiation therapy on neurocognitive functions is now well documented (Meadows et al, 1981) but, apart from rare acute toxicities (Sasazaki et al, 1992), reports on those following high-dose methotrexate are scarce, and sometimes discordant (Jannoun and Chessels, 1987; Robertson et al, 1992). Longer follow-up evaluation is warranted before definitive conclusions concerning the relationship between computed tomography scan findings and clinical outcome can be reached. The reproductive function of males is much more severely altered than that of females (Jaffe et al, 1988). Several reports have demonstrated the major dose-dependent toxicity of alkylating agents on male fertility. Male patients receiving more than 9 g/m2 of cyclophosphamide have a particularly high risk of sterility (Aubier et al, 1989) and children with less than 4 g/m2 of cyclophosphamide, a very low risk Patte et al, 1996a). Women treated before the age of 20 who do not receive abdominal irradiation usually have normal reproductive function, although early puberty (Quigley et al, 1989) and early menopause (Byrne et al, 1992) have been documented. The risk of a second malignancy is not as great as in children with a solid tumour or Hodgkin's disease (Anderson et al, 1993). The risk is higher in patients treated with alkylating agents (Lemerle et al, 1989). With the increasing cure rate, a social problem may arise for adults who "have had cancer'. The increased awareness by politicians and health insurance companies should help to solve, at least partially, this new problem (Monaco, 1987). As cure rates increase, emerging concerns involve the familial repercussions of this heavy treatment (Lansky et al, 1978; Cairns et al, 1979). At this stage, there is no demonstrated deleterious effect from treatment for the progeny of cured children (Mulvihill et al, 1987; Stein, 1993). Cure of children with lymphoma is a reality, and one should think in terms of "complete cure' when facing a distressed child with a heavy tumour burden arriving for diagnosis (Schweisguth, 1979). Since 1980, the progress of molecular biology techniques has permitted the precise molecular characterization of gene alterations (oncogenes, immunoglobulins, and T-cell receptor genes) involved in the process of malignant transformation of normal lymphocytes (Bhatia et al, 1996; Williams et al, 1996). In parallel, treatment of malignant NHL of childhood has improved dramatically. The progress in molecular biology has not led to a modification of the clinical management of NHL of childhood which remains mainly empirical. Precise cytohistological classification of lymphomas has resulted in the characterization of low- and high-risk patients requiring distinct therapeutic approaches. The major goals of the next few years will be to increase the cure rates of those patients with CNS and bone marrow involvement at diagnosis, probably through an intensification of chemotherapy (increase in the dose or intensity of the chemotherapy); to define precisely subgroups of good-prognosis patients requiring less aggressive treatment that would decrease the risk of long-term events; and to salvage previously heavily treated patients at relapse. The precise analysis of gene alterations in lymphoma cells of a given patient may have important clinical applications in this respect (Bhatia et al, 1996).