The purpose of this study was to determine the frequency of thiopurine methyltransferase (TPMT) polymorphisms in a multiracial Asian population and to assess its relevance in the management of childhood acute lymphoblastic leukemia (ALL). Six hundred unrelated cord blood samples from 200 Chinese, Malay, and Indian healthy newborns were collected at the National University Hospital, Singapore; an additional 100 children with ALL were analyzed for five of the commonly reported TPMT variant alleles using polymerase chain reaction/restriction fragment length polymorphism and allele-specific polymerase chain reaction-based assays. In the cord blood study, the TPMT*3C variant was detected in all three ethnic groups; Chinese, Malays, and Indians had allele frequencies of 3%, 2.3%, and 0.8%, respectively. The TPMT*3A variant was found only among the Indians at a low allele frequency of 0.5%. The TPMT*6 variant was found in one Malay sample. Among the children with ALL, two white and one Chinese were heterozygous for the TPMT*3A variant and showed intermediate sensitivity to 6-mercaptopurine during maintenance therapy. Three Chinese patients and one Malay patient were heterozygous for the TPMT*3C variant. Mercaptopurine sensitivity could be validated in only one out of four TPMT*3C heterozygous patients. The overall allele frequency of the TPMT variants in this multiracial population was 2.5%. The TPMT*3C was the most common variant allele; TPMT*3A and TPMT*6 were rare. These results support the feasibility of performing TPMT genotyping in all children diagnosed with acute leukemia to minimize toxicity from thiopurine chemotherapy.
The role of fiberoptic bronchoscopy for rapid diagnosis of pulmonary tuberculosis was examined among 74 patients who were suspected of having the disease but had negative sputum smear for acid fast bacilli. Bronchial brushing and washing were routinely performed in all subjects and bronchial biopsy was performed on abnormal mucosa in 7 of them. The diagnosis of pulmonary tuberculosis was confirmed in 44.6% of the patients studied from smear examination, culture, histology or the combination of them. Rapid diagnosis was achieved in 54.5% of the confirmed cases from smear or histology within a few days of examination. Two of the cases had concomitant bronchogenic carcinoma. We conclude that the fiberoptic bronchoscopy is a useful investigation for this group of patients as confirmation of the diagnosis can be made fairly rapidly in a significant proportion of them, hence the treatment can be started confidently.