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We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

We treated 18 heavily iron-loaded patients who had become ex-thalassaemics after bone marrow transplantation with subcutaneous desferrioxamine therapy for 5-20 months. As determined using serum ferritin concentration, transferrin saturation and stainable liver iron obtained in follow-up biopsies, marked decreases in body iron stores were observed with this regimen. Moreover, the liver function tests demonstrate a trend to normalization in all cases. Local skin reactions to desferrioxamine were the only toxicities observed. We conclude that pharmacological iron chelation is a safe and effective therapy in the reduction of iron deposits in this clinical situation; it therefore represents a valid alternative to phlebotomy in selected patients.

We report the reliability and safety of percutaneous liver biopsy in the evaluation of hepatic iron loading and histology in patients with homozygous beta-thalassaemia prior to and in serial biopsies following allogeneic bone marrow transplantation for this disorder. 501 thalassaemic patients aged 11 +/- 4.5 years (range 1-32 years) underwent 1184 consecutive percutaneous liver biopsies without ultrasound guidance. Overall, 81% of biopsies were evaluable for histological examination and grading of iron. The adequacy of liver biopsy specimens increased with patient age: evaluable specimens were obtained in 73% of patients < 5 years of age and in 86% of samples in patients aged > 15 years. The degree of iron overload and fibrosis in each biopsy was reported separately by at least two pathologists who did not know the clinical status of each patient. In 103 biopsies, iron grade by light microscopy corresponded to an iron concentration varying between a mean of 32.46 +/- 14 mumol/g dry weight liver tissue for iron stores graded by light microscopy as absent to 417.6 +/- 150 mumol/g dry weight liver tissue for stores graded as severe. The fibrosis score of multiple samples of liver obtained at autopsy within 100 d of the percutaneous biopsy in 41 patients who died following BMT correlated perfectly with that of the first sample in > 60% biopsies; in most of the discordant cases fibrosis had been underestimated in the percutaneous biopsy. Liver biopsy demonstrated evidence of chronic hepatitis in 30% of patients with normal transaminase and in 57% of patients with transaminase within twice the normal range. Liver biopsy was complicated in six patients (0.5%) by haemoperitoneum, periocholecystic haematoma, kidney haematoma, or bile peritonitis; no complication was fatal. These data demonstrate that percutaneous liver biopsy provides reliable information regarding liver iron and histology in homozygous beta-thalassaemia with an extremely low risk of complications.