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Background: Symptomatic osteopenia is a common form of morbidity in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. A causal role for corticosteroids has been proposed, but other investigators have suggested that cranial irradiation is an important factor contributing to this disorder., Procedure: In this study of children with ALL, all of whom received steroids, skeletal morbidity was assessed radiographically by an observer who was blinded to the ages of the children, their risk categorization (and related treatment), and the timing of the assessments with respect to the administration of therapy., Discussion: Skeletal morbidity was most prevalent in older subjects who had been given cranial radiotherapy. However, there was no difference in the frequency of fractures in two groups of younger children (< or = 9 years of age), one irradiated and the other not., Conclusions: It is likely that corticosteroid therapy plays an important part in the pathogenesis of this disorder. The role played by cranial irradiation is much less certain.

Background: The treatment of acute leukemia in childhood has been increasingly successful. Concurrently, severe leukemia-related gastrointestinal complications have become more common., Methods: We evaluated the findings of the abdominal ultrasound (US) examinations of 52 children with acute lymphoblastic leukemia (ALL) who had severe clinical symptoms indicating infection or abdominal complication during chemotherapy treatment or after the cessation of such treatment and assessed the impact of these findings on patients' subsequent treatment and survival., Results: Our study presents ten cases of typhlitis with a prevalence of 9%, all of which were rapidly diagnosed by US and had a favourable outcome. We also found focal intra-abdominal parenchymal lesions in six children, five of them due to fungal infection and one due to leukemic infiltration. Several other intra-abdominal pathologies significant for the patients' treatment are also reported., Discussion: We believe that abdominal US is a useful, rapid, safe, and accurate imaging method for children with ALL suspected to suffer from leukemia- or chemotherapy-related gastrointestinal complications. More invasive imaging methods are seldom needed., Conclusions: According to our results, abdominal US gives the necessary information in most of the cases and provides prompt diagnosis, which may prevent possible fatal complications.

The effect of cranial irradiation on possible therapy-induced morphological central nervous system (CNS) side effects of children cured from acute lymphoblastic leukemia (ALL) is controversially discussed. In a retrospective multicenter study, 118 former ALL patients in first continuous remission were investigated using cranial computerised tomography (CCT) or magnetic resonance imaging (MRI) scans to evaluate CNS related impairments. Corresponding to the different kinds of CNS prophylaxis, the patient sample was divided: group A (n = 39) receiving intrathecal methotrexate (ITMTX) and systemical medium-high-dose methotrexate (SMHDMTX), group B (n = 41) cranial irradiated (in mean 16.8 Gy) and administering ITMTX and SMHDMTX, group C (n = 38) irradiated (in mean 17.1 Gy) and getting ITMTX. Pathologic scans showed atrophy, leukoencephalopathy, calcifications or grey matter changes. These findings were compared with the neuropsychological test results. Abnormal MRI or CCI scans were found in 61/118 patients (51.7%). Fifteen belonged to group A (38.5%), 23 to B (56.1%) and 23 to C (60.5%). Patients with definite CNS changes show reduced neuropsychological test results. The prevalence of brain alterations seems to appear twice increased after lengthening the posttherapeutic interval in irradiated patients as in nonirradiated patients. Irradiated patients as an age younger than 2 years at diagnosis may show a lower prevalence for developing CNS alterations. CNS alterations are not sex-related. Children treated with cranial irradiation in combination with SMHDMTX and/or ITMTX were at greater risk of developing morphological brain alterations than patients with chemotherapy alone. These alterations are partly correlated with reduced neuropsychological performances and seem to stay with a longer posttherapeutic interval.

The survival from acute lymphoblastic leukaemia in childhood is now approximately 60-70%, and from acute myeloid leukaemia, up to 50%. However, there is little information on the effects of intensive chemotherapy and radiotherapy used in the treatment of these conditions on lung function and exercise capacity in the long term. Severity survivors of acute leukaemia from one centre in the UK were studied. Measurements of lung volumes, spirometry and transfer factor were made. Each child also performed a standard, symptom-limited maximal exercise test on a cycle ergometer. Predictive equations for indices of lung function and exercise tolerance were calculated from 146 age- and sex-matched control subjects. The results of the survivors of leukaemia were compared to these. There was a significant reduction of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and transfer for carbon monoxide (DLCO; P < 0.05 for each measurement), in the survivors of leukemia when compared to the control subjects. In addition, there was a mild but significant reduction of both maximal and submaximal indices of exercise capacity in the leukaemic group. A multivariate analysis was carried out to identify those variables acting independently to reduce lung volumes. For FEV1, FVC and TLC, these were craniospinal irradiation, cyclophosphamide and chest complications during treatment. For a reduction in DLCO, the significant factors were administration of anthracyclines, craniospinal irradiation and bone marrow transplantation. Survivors of acute leukemia have impaired pulmonary function and exercise capacity. Long-term cardiopulmonary follow-up may be necessary and new regimens devised which reduce long-term toxicity without compromising survival rates.

Cranial computed tomography (CT) was performed on 40 consecutive children with newly diagnosed acute lymphoblastic leukemia (ALL) on admission before any chemotherapy, 5 months after CNS therapy (n = 39) and after 2 to 3 years of therapy (n = 31). Changes related to leukemia were found in only 10% of the patients at the time of diagnosis (4/40). These initial changes, two intracranial hemorrhages, one dural thickening and one contrast enhancement, all disappeared during therapy. The findings which persisted unchanged in the next two CT scans were thought to be normal variations or caused by earlier disorders. CNS therapy consisted of intrathecally and intravenously administered methotrexate in 20 standard risk (SR) patients and cranial irradiation in addition to chemotherapy in 19 intermediate risk (IR) or high risk (HR) patients. Four SR patients developed changes during therapy. Three had enlarged cerebrospinal fluid (CSF) spaces and one developed a focal low density area suggesting disturbances in brain blood circulation and also experienced disturbances in level of consciousness. Of the 19 IR or HR patients, eight developed changes related to the therapy, including four with white matter hypodensity areas, of whom three also had enlarged CSF spaces, and four others who developed enlarged CSF spaces. The medians of the widths of the cortical sulci (P less than .001), insular cisterns (P less than .01), third ventricles (P less than .01), and frontal horns (P less than .05), and also of Evans' ratios (P less than .05) increased significantly after CNS therapy as compared with the findings at diagnosis in the patients who had received cranial irradiation. Most of these changes persisted during the follow-up. We conclude that the clinical value of CT scanning during therapy for ALL is restricted to patients with neurological symptoms or those who have undergone CNS irradiation.