We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.

To identify the role of iron overload in the natural history of liver fibrosis, we reviewed serial hepatic biopsy specimens taken annually from patients cured of thalassemia major by bone marrow transplantation. The patients underwent transplantation between 1983 and 1989 and did not receive any chelation or antiviral therapy. Two hundred eleven patients (mean age, 8.7 ؎ 4 years) were evaluated for a median follow-up of 64 months (interquartile range, 43-98 months) by a median number of 5 (interquartile range, 3-6) biopsy samples per patient. Hepatic iron concentration was stratified by tertiles (lower, 0.5-5.6 mg/g; medium, 5.7-12.7 mg/g; upper, 12.8-40.6 mg/g dry weight). Forty-six (22%) patients showed signs of liver fibrosis progression; the median time to progression was 51 months (interquartile range, 36-83 months). In a multivariate Cox proportional hazard model, the risk for fibrosis progression correlated to medium hepatic iron content (hazard rate, 1.9; 95% confidence interval [CI], 0.74-5.0), high hepatic iron content (hazard rate, 8.7; 95% CI, 3.6-21.0) and hepatitis C virus (HCV) infection (hazard rate, 3.1; 95% CI, 1.5-6.5). A striking increase in the risk for progression was found in the presence of both risk factors. None of the HCV-negative patients with hepatic iron content lower than 16 mg/g dry weight showed fibrosis progression, whereas all the HCV-positive patients with hepatic iron concentration greater than 22 mg/g dry weight had fibrosis progression in a minimum follow-up of 4 years. Thus, iron overload and HCV infection are independent risk factors for liver fibrosis progression, and their concomitant presence results in a striking increase in risk. IntroductionLiver fibrosis and cirrhosis are well-known complications of thalassemia, but no data are available on the risk for and rate of fibrosis progression in this disease or other posttransfusional iron overload conditions.A bone marrow transplantation (BMT) program 1 for thalassemia has been operational in Pesaro, Italy since 1983. At that time there was no knowledge of the effect of iron overload and chelation therapy after BMT; therefore, watchful waiting through periodic percutaneous liver biopsy was established for all patients cured of thalassemia by BMT. These patients were affected by iron overload but did not receive any chelation therapy. Before entering an effective iron reduction program, they had stable liver iron levels and represented unique model group to study the natural history of liver fibrosis in this condition. Thus, all the hepatic biopsies performed during this watchful waiting program have been blindly re-evaluated to assess the risk for and the rate of fibrosis progression. Patients and methods Study populationPatients cured of thalassemia by BMT in Pesaro took part in a watchful waiting program based on yearly liver biopsy to monitor unanticipated complications of marrow transplantation and iron overload. All these patients had received unmodified bone marrow from an HLA-identical related donor. All but 4 we...

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We report the reliability and safety of percutaneous liver biopsy in the evaluation of hepatic iron loading and histology in patients with homozygous /3thalassaemia 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

In some patients in whom bone marrow transplantation has cured thalassemia, cirrhosis may be reversible after iron removal treatment.