Since the number of children receiving a bone marrow transplantation (BMT) and becoming long-term survivors continues to increase, more attention 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 longer life expectancy of children cured by BMT. The more frequently recognized sequelae affecting lung, eyes, brain and the endocrine system have been analyzed in this review. The majority of long-term side effects could be related to the conditioning regimens employed to prepare children before marrow transplantation and radiotherapy has been indicated as the most important agent determining deleterious toxicities. Most children receiving BMT present a decreased growth velocity and this growth impairment is especially observed in patients receiving total body irradiation (TBI) and prophylactic cranial irradiation prior to marrow transplant. Growth hormone deficiency could be demonstrated in the majority of patients with a reduced growth rate, even though an impairment of liver somatomedin production or a direct radiation-induced skeletal dysplasia could not be excluded. Overt and compensated hypothyroidism have been reported after TBI and patients given single dose radiotherapy are at greater risk with an overall incidence of thyroid function abnormalities approaching 30-40%. Delayed puberty development was reported in boys and girls after a TBI-containing conditioning regimen, whereas patients given BMT for severe aplastic anaemia presented a normal puberty. The absence of pubertal growth spurt contributes to the growth impairment of prepubertal children. In post-pubertal patients amenorrhea, azoospermia and gonadal failure can be observed after radiotherapy and several patients can require hormonal substitutive therapy. Skin and mucosal abnormalities referred to teguments involvement by chronic graft-versus-host disease (GVHD). Moreover, alopecia or abnormal pigmentation of the skin are observed in patients given busulfan as part of their myeloablative therapy. Cataracts are a well recognized complication of children receiving ionizing radiations and chronic steroid therapy. Again, posterior subcapsular cataracts occur more frequently in patients given TB1 as single exposure. Decreased lacrimal gland function, with impairment of tear production is another late effect of irradiation to the eye. Lung function abnormalities are not rare after transplant and may cause late mortality and morbidity. These abnormalites include late onset interstitial pneumonitis, restrictive changes and bronchiolitis obliterans. Radiotherapy, drugs such as busulfan and BCNU, chronic GHVD occurrence, GVHD prophylakis with methotrexate are known risk factors. Multifocal leukoencephalopathy can occur in children receiving a marrow transplant after a TBI-containing myeloablative therapy, especially in those who had received prophylactic cranial irradiation during first line chemotherapy. An impairment of cognitive function (i.e. learning difficulties, low IQ scores) can be observed and the recognized risk factors are similar to those above mentioned for the development of multifocal leukoencephalopathy. Finally it must be mentioned that due to their longer life expectancy children are at particular risk of developing secondary malignancies, whose main risk factors are represented by GVHD occurrence, treatment of GVHD with antilymphocyte globulin and monoclonal antibodies, ex-vivo T-cell depletion and radiotherapy.
