Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes

Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, β-thalassemia/hemoglobin E (β-thal/E) with transfusion-dependency (TD) (n = 18); 2, β-thal/E with transfusion-independency (TI) (n = 15); 3, β-thalassemia major (β-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT₄) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the β-major and β-thal/E with TD groups were not significantly different. In comparison with the β-major and β-thal/E with TD groups, the β-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the β-major, β-thal/E with TI, and HbH groups were significantly lower than those of the β-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.     

Hemophilia treatment in developing countries: products and protocols

The most important aspect of management of hemophilia is to provide adequate replacement of safe clotting factor concentrates to prevent or treat bleeding episodes. There has been considerable progress in many countries in the developing world with regard to this aspect of care. However, very little data are available in the literature on the types of products being used for factor replacement and the doses being administered for control or treatment of bleeding in different countries. These data are important to document because only then can data from different centers be compared. This article provides data from seven countries: Korea, Malaysia, Thailand, Venezuela, Argentina, Iran, and India. It shows that there is wide variability not only in the types of products used (plasma to recombinant factor concentrates) but also in the doses administered (minimal to very high) for similar indications. Prospective documentation of data on musculoskeletal outcome at these centers and correlation with dose of factor replacement could help identify different models of care. Comparing such data and collating the experience in different countries could be useful for optimizing care and establishing cost-effective models. The combined experience in the developing world in providing hemophilia services should be used to define standards of care that are practical and to set achievable goals.     

Allogeneic bone marrow transplantation in an osteopetrosis patient: first report in Thailand

We described the successful allogeneic matched sibling bone marrow transplantation (BMT) in a 5-year-old Thai boy in whom osteopetrosis was diagnosed on the basis of anemia, thrombocytopenia, leukoerythroblastosis, sclerotic bone, hepatosplenomegaly, and visual deficit from an encroachment of cranial nerve foramina. The preparative regimen included 4 days of busulfan 4 mg/kg/day, and 4 days of cyclophosphamide 50 mg/kg/day. Complete hematopoietic engraftment and no evidence of graft versus host disease were shown after BMT. Complete hematologic findings were corrected. His hematopoietic chimerism was changed to that of his donor. Post BMT, he has no hepatosplenomegaly. His bone radiographic findings revealed normal after BMT. Bone marrow biopsy showed normalized bone and bone marrow matrix. However, his vision remained impaired. We believe that this is the first case of successful bone marrow transplantation in an osteopetrosis patient in Thailand.     

Successful allogeneic peripheral blood stem cell transplantation in Wiskott-Aldrich Syndrome Patients: first report in Thailand

Wiskott-Aldrich syndrome (WAS), an X-linked recessive disorder, is characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody production, eczema, and thrombocytopenia. Stem cell transplantation is the only curative therapy. To evaluate the use of allogeneic peripheral stem cell transplantation (PBSCT) in this group of patients, we performed allogeneic PBSCT in two WAS patients (3 and 12 years old). The conditioning regimen consisted of busulfan 4 mg/kg/day for 4 days, and cyclophosphamide 50 mg/kg/day for 4 days. Graft-versus-host disease prophylaxis was consistent with cyclosporin A and methotrexate. Peripheral blood stem cells were collected from their brother donors (6 and 16 years old) by continuous flow leukapheresis after mobilization with granulocyte-colony-stimulating factor at a dose of 7.5 microg/kg/day for 5 days. Both recipients achieved neutrophils engraftment on days 11 and 12. The first patient achieved platelets engraftment on day 30. The second patient did not have platelet count below 20.0 x 10(9)/l during PBSCT procedure. Both did not develop acute or chronic graft-versus-host disease. At present, they are healthy after PBSCT. The follow up time after transplantation is 1,170 days and 269 days, respectively. Allogeneic PBSCT is economically feasible for WAS. The cost of PBSCT in Thailand is 20 to 30% less than bone marrow and cord blood stem cell transplantation. The cost of the transplant procedure for each patient in Thailand is US $ 12,000. This study is the first report of a successful stem cell transplantation in WAS patients in Thailand.     

Venous thromboembolism in Thai children

This is a retrospective study of 24 pediatric venous thromboembolism (VTE) patients with or without pulmonary embolism, conducted in Bangkok, Thailand, between 1981 and 2005. The incidence rate of VTE in Thai children was 3.9/10,000 hospital admissions per year. The median age was 11.7 years. Seventy-five percent of the patients had at least one associated medical condition accounting for the VTE; the two most common conditions, however, were infection and malignancy. Pulmonary embolism occurred in 29% of patients. Observed outcomes of VTE in this series included death (13%), postphlebitic syndrome (13%), and recurrence (26%). Genetic risk factors were explored in 19 patients, and no factor V Leiden or prothrombin 20210 mutations were detected. Protein C deficiency was found in 4 patients.     

Intramuscular anti‐D in chronic immune thrombocytopenia children with severe thrombocytopenia

Nine patients with chronic immune thrombocytopenia and platelet counts <20 × 10⁹/L, with a median age of 7.8 (3.8–15.5) years, received three phases of 10 mcg/kg/dose of intramuscular anti‐D. Phase 1 was anti‐D daily for 5 days, followed by phase 2, anti‐D weekly for 12 weeks and withheld when platelet counts ≥20 × 10⁹/L, and then phase 3 was anti‐D once every 2 weeks for 24 weeks. According to the International Working Group criteria, in phase 1, 66.7% of patients responded to the treatment. In phases 2 and 3, 11.1% (0–41.7%) and 7.7% (0–33.3%) of total episodes of follow up, respectively, responded to the treatment. Therefore, intramuscular anti‐D given at a dose of 10 mcg/kg for 5 days is an alternative method to raise platelet counts in chronic immune thrombocytopenia children with severe thrombocytopenia where the intravenous form of anti‐D is not available.