Morbidity and mortality patterns of thalassaemia major patients in Hong Kong: retrospective study.

OBJECTIVES: To study the morbidity and mortality patterns of transfusion-dependent thalassaemia major patients in Hong Kong, and compare the outcomes of these patients according to different periods of birth. DESIGN: Retrospective study. SETTING: Paediatric departments of three regional hospitals, Hong Kong. SUBJECTS AND METHODS: Medical records of thalassaemia major patients were reviewed. Data gathered included demographic and survival data, complications of iron overload, repeated transfusion, and bone marrow transplantation; the probability of survival of three cohorts was also estimated. RESULTS: Two hundred and thirty-two patients were studied at a median age of 15.5 years (range, 1.4-30.3 years). There were 60 patients born before 1980 (cohort 1), 117 patients born between 1980 and 1989 (cohort 2), and 55 patients born after 1989 (cohort 3). The median age of starting desferrioxamine was 8 years, 4 years, and 3 years for cohorts 1, 2, and 3, respectively. Cardiomyopathy, diabetes mellitus, and hypothyroidism occurred in 15.1%, 8.6%, and 6.9% of patients with thalassaemia major, respectively. The above complications developed in 5% to 12% of cohort 2 patients. Delayed puberty was present in 38.4% and hormonal replacement for gonadal failure was required in 29.7% of evaluable patients. Short stature was common and the median height standard deviation score was -1.63. Twenty patients had died, and cardiomyopathy was the leading cause of death, followed by complications of bone marrow transplantation. The probability of survival beyond the age of 20 years was 87.6%. CONCLUSION: Despite the use of iron chelation in the past two decades, severe complications of iron overload still occurred even in those who started chelation therapy early. Cardiomyopathy was the leading cause of death, while endocrinopathies and short stature were common complications especially in teenagers and adults.

Liver disease in transfusion dependent thalassaemia major.

AIMS: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. METHOD: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). RESULTS: One hundred patients were evaluated (median age 11.7 years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. CONCLUSION: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.

Deferoxamine-induced dysplasia of the knee: sonographic features and diagnostic performance compared with magnetic resonance imaging.

OBJECTIVE: To evaluate the features and diagnostic performance of sonography in the assessment of deferoxamine-induced dysplasia of the knee. METHODS: The left knees of 32 patients with thalassemia who were receiving regular blood transfusions and chelation therapy were studied with sonography for signs of deferoxamine-induced bone dysplasia. Abnormal physeal and metaphyseal changes detected on sonography included notching at the metaphyseal corner, a blurred or irregular peripheral juxtaphyseal metaphyseal contour, and widening of the peripheral juxtaphyseal metaphyseal echogenic interface. The accuracy of sonography in diagnosing dysplasia was evaluated by using magnetic resonance imaging as the standard of reference. RESULTS: There were 14 true-positive findings, 10 true-negative findings, 7 false-negative findings, and 1 false-positive sonographic diagnosis of dysplasia, giving 67% sensitivity, 91% specificity, a 93% positive predictive value, and a 59% negative predictive value. CONCLUSION: Sonography was specific but only moderately sensitive in the diagnosis of deferoxamine-induced dysplasia at the knee when compared with magnetic resonance imaging.

Deferoxamine-induced bone dysplasia in the distal femur and patella of pediatric patients and young adults: MR imaging appearance.

OBJECTIVE: We investigated the MR imaging appearance of deferoxamine-induced bone dysplasia in the distal femur and patella in patients with thalassemia major. MATERIALS AND METHODS: Thirty-five patients with homozygous ss-thalassemia major who were undergoing regular transfusions and chelation therapy underwent coronal T1-weighted MR imaging of the femur, including the femoral head and the distal femoral epiphysis. Additional coronal fat-saturated dual-echo and sagittal T1-weighted images of the distal femur and patella were obtained in 11 patients who were suspected of having distal femoral lesions on the basis of the coronal T1-weighted images of the entire femur. RESULTS: No dysplastic change was detected in the proximal femur on coronal T1-weighted images. In 22 distal femurs of 11 patients, the following abnormalities were detected on MR imaging: blurred physeal-metaphyseal junction (n = 22), distal metaphyseal areas of hyperintensity (n = 21), physeal widening (n = 18), metadiaphyseal lesions (n = 11), epiphyseal lesions (n = 10), and patellar lesions (n = 2). Physeal widening and distal metaphyseal hyperintense areas were all more pronounced peripherally. Of the 21 distal metaphyseal hyperintensities, lateral abnormalities were larger than medial abnormalities in 16. Of the 18 distal femurs in which physeal widening was detected, the lateral widening was more marked than the medial widening in 12. Patients with MR imaging evidence of bone dysplasia have a significantly (p = 0.003) greater height reduction than patients without such evidence of bone dysplasia. CONCLUSION: Deferoxamine-induced bone dysplasia in the distal femur and patella is represented by a spectrum of morphologic changes in the epiphysis, physis, metaphysis, and metadiaphysis on MR imaging.

Desferrioxamine-induced long bone changes in thalassaemic patients - radiographic features, prevalence and relations with growth.

AIM: To study the radiographic findings of desferrioxamine-induced bone dysplasia, its prevalence and relation to growth in thalassaemic patients. MATERIALS AND METHODS: A cross-sectional study was performed in 35 thalassaemic patients on a hypertransfusion scheme and chelation therapy at a dose not exceeding 50 mg/kg/day. Radiographs of the left hand taken for bone age assessment in consecutive patients over the past 12 months were evaluated for signs of desferrioxamine-induced bone dysplasia. The findings were correlated with data on growth, chelation and body iron content. RESULTS: Twelve of 35 patients had evidence of desferrioxamine-induced long bone dysplasia. There was no significant difference in the groups with and without radiographic evidence of bone dysplasia with respect to the height percentile at time of initiation of therapy, height percentile at time of radiography, skeletal age delay, age at starting chelation, chelation dose and duration, units of blood transfused, average chelation dose, and serum ferritin levels at time of radiography. Both groups showed a reduced percentile growth with a significantly greater reduction (P = 0.03) in the patients with dysplastic change. CONCLUSION: Desferrioxamine-induced bone dysplasia is associated with height reduction and can be seen in patients receiving desferrioxamine chelation therapy at doses of less than 50 mg/kg/day. Awareness of the diagnosis is of importance as reduction of the desferrioxamine dose may improve bone growth.

Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation.

We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167-172.