LATE EFFECTS IN CHILDREN AFTER BONE-MARROW TRANSPLANTATION - A REVIEW

Since the number of children receiving a bone marrow transplantation ( BMT) and becoming long-term survivors continues to increase, more atte ntion has to be paid to detect long-term side effects in these unique patients. Follow-up studies to timely identify these untoward sequelae are a matter of particular concern for pediatricians due to the longe r life expectancy of children cured by BMT. The more frequently recogn ized sequelae affecting lung, eyes, brain and the endocrine system hav e been analyzed in this review. The majority of long-term side effects could be related to the conditioning regimens employed to prepare chi ldren before marrow transplantation and radiotherapy has been indicate d as the most important agent determining deleterious toxicities. Most children receiving BMT present a decreased growth velocity and this g rowth impairment is especially observed in patients receiving total bo dy irradiation (TBI) and prophylactic cranial irradiation prior to mar row transplant. Growth hormone deficiency could be demonstrated in the majority of patients with a reduced growth rate, even though an impai rment of liver somatomedin production or a direct radiation-induced sk eletal dysplasia could not be excluded. Overt and compensated hypothyr oidism have been reported after TBI and patients given single dose rad iotherapy are at greater risk with an overall incidence of thyroid fun ction abnormalities approaching 30-40%. Delayed puberty development wa s reported in boys and girls after a TBI-containing conditioning regim en, whereas patients given BMT for severe aplastic anaemia presented a normal puberty. The absence of pubertal growth spurt contributes to t he growth impairment of prepubertal children. In post-pubertal patient s amenorrhea, azoospermia and gonadal failure can be observed after ra diotherapy and several patients can require hormonal substitutive ther apy. Skin and mucosal abnormalities referred to teguments involvement by chronic graft-versus-host disease (GVHD). Moreover, alopecia or abn ormal pigmentation of the skin are observed in patients given busulfan as part of their myeloablative therapy. Cataracts are a well recogniz ed complication of children receiving ionizing radiations and chronic steroid therapy. Again, posterior subcapsular cataracts occur more fre quently in patients given TB1 as single exposure. Decreased lacrimal g land function, with impairment of tear production is another late effe ct of irradiation to the eye. Lung function abnormalities are not rare after transplant and may cause late mortality and morbidity. These ab normalites include late onset interstitial pneumonitis, restrictive ch anges and bronchiolitis obliterans. Radiotherapy, drugs such as busulf an and BCNU, chronic GHVD occurrence, GVHD prophylakis with methotrexa te are known risk factors. Multifocal leukoencephalopathy can occur in children receiving a marrow transplant after a TBI-containing myeloab lative therapy, especially in those who had received prophylactic cran ial irradiation during first line chemotherapy. An impairment of cogni tive function (i.e. learning difficulties, low IQ scores) can be obser ved and the recognized risk factors are similar to those above mention ed for the development of multifocal leukoencephalopathy. Finally it m ust be mentioned that due to their longer life expectancy children are at particular risk of developing secondary malignancies, whose main r isk factors are represented by GVHD occurrence, treatment of GVHD with antilymphocyte globulin and monoclonal antibodies, ex-vivo T-cell dep letion and radiotherapy.