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Aim: Homozygous alpha-thalassaemia, also called haemoglobin (Hb) Bart's hydrops fetalis, has been thought to be a lethal condition. Due to prenatal diagnosis and intrauterine blood transfusions, a few patients with Hb Bart's hydrops fetalis have survived. This fact raises the urgent questions of clinical management and appropriate follow-up of these patients, both of which are addressed in this article., Methods: We report on a 6.5-y-old patient with homozygous alpha-thalassaemia and review the literature of 13 other survivors published to date. Transfusion requirements were evaluated and the rate of liver iron accumulation was assessed by biomagnetic liver susceptometry before and after institution of iron-chelating therapy. Psychometric evaluation was carried out using Munich's Functional Development Test, the Columbia Mental Maturity Scale, the Kaufman Assessment Battery for Children, and the Peabody Picture Vocabulary Test., Results: Our patient had significant delay of psychomotor development. Psychometric evaluation at the age of 5 y revealed an IQ of 85 and an intellectual level of a 4-y-old child. Early tissue iron overload was seen, but a negative iron balance was achieved after institution of desferrioxamine treatment at dosages used for beta-thalassaemia., Conclusion: Homozygous alpha-thalassaemia should no longer be regarded as a lethal condition. Early intervention during pregnancy and careful haematological as well as neuropsychological follow-up was able to provide long-term survival and good life quality in our patient.

Haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs. Cure seems possible only by allogeneic bone marrow transplantation (BMT), but matched sibling donors (MSD) are restricted and high mortality rates are associated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD. Five patients had signs of active HLH at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulphan, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a fivefold graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild in 10, and moderate or severe in two patients undergoing unrelated transplants. One patient with URD experienced graft failure and was retransplanted on day 37. Major toxicities were hepatic veno-occlusive disease in five, capillary leak syndrome in two, pneumonia in three, sepsis in one, severe mucositis in one and seizures in two patients. All patients are alive without HLH after a median follow-up of 24.5 months. One patient has chronic GVHD, another patient has severe retardation. Three patients show slight to moderate development delay. These results indicate that in HLH, BMT from matched unrelated donors should be performed. Incomplete resolution of disease activity need not impede a successful outcome.

To investigate the applicability of noninvasive Superconducting Quantum Interference Device (SQUID) biomagnetic liver susceptometry and its limitations in thalassemic children, 23 patients with beta-thalassemia major and other iron loading anemias (age: 4-16 years) and 16 age-related normal children were studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for thalassemic patients and from 60 to 340 microg/g(liver) for normal patients. Measuring the respective organ volumes by sonography, liver and spleen iron stores, accounting for 80% of total body iron stores, were estimated. Nonliver contributions from the lung or intestine to the measured SQUID signals in the small-sized patients were not observed. Moreover, livers in thalassemia were found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)), but predict iron stores only within large error intervals of 4,000 microg/g(liver). Analyzing the experimental data from biomagnetometry and from related transfusion and chelation treatment data within the framework of a two-compartment model, we were able to derive additional information on total body iron elimination and chelation therapy efficacy. The exponential decline of iron stores allows forecast of steady-state conditions of the final iron load for a particular transfusion and chelation therapy regimen.