Brief report: transplantation of cord-blood stem cells into a patient with severe thalassemia.
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Biomedical subjects
Publications and source records attributed to V S Tanphaichitr.
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Thailand. This condition can cause acute hemolysis during oxidative stress and also severe hyperbilirubinemia in the newborn in some populations. Our aim was to study the prevalence of G6PD deficiency in relation to neonatal jaundice. We performed quantitative red blood cell (RBC) G6PD assay in the cord blood of 505 male subjects. Observation of jaundice and determination of bilirubin level as well as work up for other causes of jaundice were made in the G6PD deficiency group compared to a G6PD normal group. Questionnaires were also sent for further follow up to both groups. The results of the study were as follows: Sixty-one of 505 male (12.08%) had RBC G6PD deficiency (Group I). The rest (444 cases) had normal G6PD (Group II). In Group I, 49.15% developed neonatal jaundice, of which 28.82% were physiologic and 20.33% were pathologic jaundice. In group II, 23.68% developed jaundice; 16.51% were physiologic and 7.17% were pathologic jaundice, respectively. Onset of jaundice, date of peak bilirubin and peak bilirubin level in Group I and Group II were not statistically different. ABO incompatibility was associated with Group I in 17.24% and with Group II in 9.09%. Hospitalization day in Groups I and II were not statistically different. Other associated diseases were found in both groups, ie infection, congenital malformation, respiratory distress syndrome, but there was no significant difference in terms of jaundice. Phototherapy was required in 18.64% and 10.28% in Group I and II with a duration of 3.91 +/- 1.24 and 3.21 +/- 1.75 days, respectively. One case in Group I who was also premature received one exchange blood transfusion due to severe sepsis but he did not survive. One case in Group II who had polycythemia was successfully treated by partial exchange transfusion with plasma.
Thalassemia hemoglobinopathies and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are prevalent in Thailand. We studied the prevalence of these disorders from 1,000 cord bloods collected during 14 months period, using EDTA as anticoagulant. Red blood cell G-6-PD quantitative assay was performed in all male subjects. Nine hundred and eighty five specimens were available for hemoglobin (Hb) typing by starch gel electrophoresis. Further evaluation by cellulose acetate electrophoresis and follow up were made in the cases who had Hb E and/or high level of Hb Bart's. It was found that out of 505 males, 61 cases (12.08%) had G-6-PD deficiency. Among 985 cases studied for Hb typing, 61.92% revealed normal Hb type AF while Hb E was present in 18.68% and Hb Bart's designated alpha-thalassemias were present in 25.18% respectively. Of these 985 cases, 18.78% had low Hb Bart's level ie detectable to 8.2% consistent with alpha-thal2, Hb Constant Spring (CS) or alpha-thal1 trait. Ten cases (1.02%) had high levels of Hb Bart's ranging from 16.1-35% without or with Hb CS and E, and further follow-up revealed homozygous Hb CS, Hb A-E-Bart's, Hb H and Hb H with Hb CS disease. The other 53 cases (5.38%) had low level of Hb Bart's with Hb E consistent with alpha-thalassemia trait with Hb E trait. There were 127 cases (12.89%) who had only Hb E trait and 3 cases (0.3%) who had Hb F and E without Hb A initially.
The immunogenicity and the protective efficacy of a recombinant DNA hepatitis B vaccine, GenHevac B Pasteur with or without passive immunization with hepatitis B immunoglobulin (HBIG) in high risk neonates born from HBsAg and HBeAg positive mothers was evaluated. Twenty-six neonates (group A) received HBIG 100 IU intramuscularly at birth plus GenHevac B Pasteur 20 micrograms at birth, 1, 2 and 12 months of age while another 23 neonates (group B) received only GenHevac B Pasteur vaccine. Forty high risk newborns who received no immunization served as control group. It was found that at months 4, 12, 13 and 24 the seroconversion rate in both group A and B were very high in the range of 95-100% with the GMT ranging from 10-160,000 mlU/ml. In the control group of infants, 85% had HBsAg positive at one year of age but it was only 3.8% and 8.7% in vaccinated groups A and B, respectively. The protective efficacy in neonates group A and B were 95.5% and 89.8% at one year, respectively, with no statistically significant difference. In 46 normal school children (group C) and 48 healthy adults (group D) who received the same dose of GenHevac B Pasteur the seroconversion rates at month 4 after receiving 3 doses of vaccination were 97.8% and 83.3% in group C and group D, respectively. At month 12, the seroconversion rate in group C rose to 100% and was significantly higher than the 89.6% of group D.(ABSTRACT TRUNCATED AT 250 WORDS)
We report our experience of bone marrow transplantation for thalassemia in Thailand. From July 1988 to September 1992, 10 thalassemic patients underwent allogeneic bone marrow transplantation. Two of them were homozygous beta-thalassemia and 8 were beta-thalassemia/Hb E disease. Seven were male and 3 female. The age ranged from 1.8-14 years. The conditioning regimen comprised busulfan 14 mg/kg and cyclophosphamide 200 mg/kg. For GVHD prophylaxis, either cyclosporine alone or in combination with short methotrexate was given. Five patients were alive and well 104-1534 days after transplantation. Three patients with severe manifestations at the time of transplant had partial engraftment, and lost their graft within 3 months. They survived with thalassemia 1041-1357 days after transplantation. One patient who received one antigen mismatched marrow from her brother had no engraftment and was alive with thalassemia 1429 days posttransplant. One patient died early on day 9 from CNS complication. No GVHD was observed in this series. These results indicate that bone marrow transplantation can cure thalassemia but there is still high autologous recovery rate in those with severe manifestations.
Passive and active immunization for the prevention of hepatitis B virus (HBV) transmission in neonates born to HBeAg positive carrier mothers was studied using different kinds and dosages of combined hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine. The long term efficacy of these various immunoprophylaxis programmes was evaluated up to 3 years of age. Eight groups of neonates, 20 in each group, received HBIG either the usual dose of 100 IU intramuscularly or intravenously or increased dose to 200 IU, combined with different kinds of hepatitis B vaccine either in full dose or half dose given in different schedules of 0, 1, 2 or 0, 1, 6 months, in some groups also received a booster dose at 12 months. After follow-up for 3 years, there were no statistical significant differences of the results between these 8 different immunoprophylaxis programmes, either in the rate of seroconversion or the protective efficacy as well as the antibody response (anti-HBs titer). The seroconversion rates after 3 years of age in all 8 groups were in the range of 63.6 to 92.9 per cent. The protective efficacy rates at 3 years of age were in the range of 69.7 to 100 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemoglobin Constant Spring (Hb CS) is a hemoglobin variant with an elongated alpha-globin chain secondary to a chain termination mutation. The diagnosis of HbCS by electrophoresis is difficult because it is present in very low amounts in the red cells of heterozygotes. Selective enzymatic amplification of the alpha 2-globin gene and allele-specific hybridization for Hb CS gene provided accurate diagnosis of Hb Constant Spring. We have used this approach to detect the alpha cs mutation in the cord blood that contained all four alpha-globin genes but had Hb Bart on electrophoresis. The alpha cs mutation was found in six subjects whose Hb Bart levels were 3.0, 3.2, 3.7, 4.0, 4.9, and 9.8%. The latter also had -alpha mutation on the other chromosome, giving rise to the genotype alpha cs alpha/-alpha, which produced high Hb Bart. The gene frequency for alpha cs in the Thai calculated from a total of 406 cord blood studied in Bangkok was found to be approximately 0.008.
An 11-year-old boy who presented with anemia, premature grey hair, hyperpigmented skin, paresthesia, recurrent aphthous ulcers and epistaxis was eventually proved to be a case of vitamin B12 deficiency. Due to the paucity of this deficiency, the diagnosis may easily be delayed and overlooked resulting in unfavorable consequences. Therapeutic response to vitamin B12 was dramatic in this reported case.
A low dose of recombinant DNA hepatitis B vaccine (HB-VAX II, MSD) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in normal and high-risk neonates born from HBsAg carrier mothers. A dose of 2.5 micrograms recombinant vaccine was injected intramuscularly at 0, 1, 2 and 12 months of age to 30 newborns from HBsAg negative mother (group I), 30 from HBeAg negative/HBsAg carrier mother (group II) and 30 from HBeAg positive/HBsAg carrier mother (group III). The incidence of persistent HBsAg carrier infants at 13 months of age was 0, 0, and 30.4 percent in groups I, II and III, respectively. The protective efficacy in high risk infants in group III was 65.7 percent. The seroconversion at month 4, after the third dose of vaccination was 96.3, 95.7 and 100 percent in group I, group II and group III, respectively. After a booster dose of vaccination at 12 months of age, the seroconversion rose to 100 percent at month 13 in all three groups. The geometric mean titer (GMT) of anti-HBs antibody at 13 months of age were 2,092, 1,657 and 1,938 mIU/ml in group I, group II and group III, respectively. It is concluded that the low dose (2.5 micrograms) recombinant hepatitis B vaccine using alone is effective in prevention of perinatal HBV transmission in low risk infants (groups I and II), but it is less effective in high risk infants (group III).(ABSTRACT TRUNCATED AT 250 WORDS)
A first case of subcutaneous infection caused by Saksenaea vasiformis in an 11-year-old Thai thalassaemic boy was described. The specific diagnosis of infection was attained from microscopic demonstration of the causal agent as well as the isolation of the fungus. The patient was successfully treated by debridement of the lesion and parenteral amphotericin B. The predisposing factors, source of infection and regimen for treatment are discussed.
Three cases of sinus histiocytosis with massive lymphadenopathy are reported in Thai children and is probably a first report in Thailand. They were clinically characterized by bilateral massive cervical lymphadenopathy. Other lymph node groups were also involved but no extranodal manifestations could be detected. Leukocytosis with neutrophilia, hypergammaglobulinemia and polyclonal gammopathy were common features. The characteristic histopathologic findings in the involved lymph nodes included pericapsular fibrosis, markedly dilatation of subcapsular and medullary sinuses which were filled with numerous histiocytes showing active phagocytosis of lymphocytes and lymphoplasmacytoid proliferation in paracortical strands and medullary cord. The disease characteristically has a benign protracted clinical course, and does not respond to either irradiation or chemotherapy. The etiology and pathogenesis of this disorder are unknown. The possible pathologic mechanisms include an abnormal response to a specific infectious process and an immune deficiency status.
Nineteen children and adolescents in long-term complete remission from acute lymphoblastic leukemia (ALL) were studied for hormonal and growth status after cessation of therapy. Cranial irradiation of 600-2,400 cGy was given for C.N.S. prophylaxis in 18 out of 19 patients, and additional irradiation of 2,000 cGy was given to both testes of a prepubertal boy because of testicular infiltration. The time ranges after cranial irradiation and cessation of therapy at the time of study were 61-137 months and 5-127 months respectively. Thyroid hormone, cortisol and peak cortisol response after ACTH stimulation were normal in every tested children. Basal serum gonadotropin and sex steroid values were appropriate in the majority of patients. A child who received testicular irradiation, had elevated levels of gonadotropins. Glucagon stimulation test (GST) and/or L-Dopa propranolol test (DP test) were used to study growth hormone (GH) response. None had peak GH value less than 7 ng/ml. Ten patients had peak GH values of over 15 ng/ml. Nine female patients had normal puberty and regular menstruation. Eight out of ten male children also had normal puberty. All except two male patients had normal linear growth within 2 standard deviations of the mean. The mean attained final height of 11 children was not significantly different when compared to the mean predicted heights obtained from Bayley-Pinneau and Tanner methods. Excessive weight gain during and after cessation of chemotherapy was observed in the majority of children. Continuing long-term review of these children is essential.(ABSTRACT TRUNCATED AT 250 WORDS)
Massive chemotherapy and autologous bone marrow transplantation (ABMT) have been successfully used for the treatment of Burkitt's lymphoma. We report our first success with such treatment in two children with Burkitt's lymphoma in Thailand. Both patients had massive abdominal tumors with ascites and minimal bone marrow metastasis at the first presentation. They received induction chemotherapy and intensive treatment including central nervous system prophylaxis with cranial irradiation and intrathecal methotrexate until being in complete remission before starting massive chemotherapy, comprising the combination of BCNU, cytosine arabinoside, cyclophosphamide and 6-thioguanine followed by ABMT. Both patients recovered completely following intensive supportive treatments post ABMT and are still good health without evidence of the disease for 18 and 8 months after transplantation respectively. The role of massive chemotherapy and ABMT for the treatment of non-Hodgkin's lymphoma especially Burkitt's lymphoma was discussed.
beta-Thalassemia mutations in 71 chromosomes of Thai patients from the northeast, the middle and the south of the country were investigated using dot blot hybridization of PCR (polymerase chain reaction)-amplified DNA with allele-specific oligonucleotide probes. Eight different known molecular defects were detected, at different frequencies. There was an amber mutation in codon 17, a C-T transversion at position 654 of IVS-2, a frameshift mutation between codons 71 and 72, an A-G transition at nucleotide -28 within the TATA box (known as Chinese mutations), a G-T transversion at position 1 of IVS-1 (an Indian mutation), a 4 bp deletion in codons 41/42 and a G-C transversion at position 5 of IVS-1 (described as both Chinese and Indian mutations) and a Thai original mutation, an ochre mutation in codon 35. Analysis of the three unknown alleles by DNA sequencing of the cloned DNA fragment amplified by PCR revealed an A-G substitution at the second position of the codon for amino acid 19 (AAC-AGC). The analytic approach used in the present study and the characteristic distribution of mutations in each region of Thailand will prove useful for setting up a prenatal diagnosis program.
Post-transfusion hypertension, convulsion and cerebral haemorrhage is a serious complication that may occur in the thalassaemias. In this study we evaluated the effect of blood transfusion on blood pressure, plasma renin activity (PRA), blood viscosity, and urinary vanillylmandelic acid (VMA) and catecholamines in 11 beta-thalassaemia/haemoglobin E patients. The results showed that after each unit of blood transfusion the blood viscosity was increased and correlated with the increased in haematocrit level. At the same time the PRA level was significantly decreased and tended to return to the normal level in a few days after the transfusion. There was no alteration in the urinary VMA and catecholamine levels. During the study two patients developed hypertension and headache. Their PRA were still lower than the pre-transfusion levels and the blood pressure returned to the normal pre-transfusion levels within 30-90 minutes after the intravenous injection of furosemide.
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