Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. It is now well established that interindividual variation in sensitivity to thiopurines can be the result of the presence of genetic polymorphisms in the TPMT gene. The aim of this study was to determine the frequency and type of TPMT polymorphisms in the population of Serbia and Montenegro and to assess its relevance in the management of childhood acute lymphoblastic leukemia (ALL). Blood samples from 100 healthy adults and 100 children with ALL were analyzed for common mutations in the TPMT gene using polymerase chain reaction-based assays. The results revealed that allelic frequencies were 0.2% for TPMT*2, 3.2% for TPMT*3A, and 0.5% for TPMT*3B. A rare TPMT*3B allele was detected in 2 families. No TPMT*3C allele was found. The general pattern of TPMT-variant allele distribution as well as their frequencies in the population of Serbia and Montenegro, is similar to those determined for other Slavic and Mediterranean populations. The ability to tolerate 6-mercaptopurine (6-MP) -based maintenance therapy was used as a surrogate marker of hematologic toxicity. In the study of 50 patients with childhood ALL treated according to the BFM-like protocol, it was found that even TPMT-heterozygous patients are at greater risk of thiopurine drug-related leukopenia (mean duration of period when children missed therapy as a result of leukopenia for TPMT-heterozygous patients was 11.3 weeks vs 3.4 weeks for wild-type genotype patients, P < 0.01). In another group of 50 patients, the TPMT genotype was determined prospectively. The therapy protocol was modified considering their TPMT genotype. Administering reduced 6-MP dosages in the initial phase of maintenance allowed TPMT-heterozygous patients to later receive full protocol doses of both 6-MP and nonthiopurine therapy without omitting therapy resulting from myelotoxicity. These results justify performing TPMT genotyping before initiating thiopurine therapy in all children with ALL to minimize consequent toxicity.

Kasabach-Merritt syndrome denotes profound thrombocytopenia and coagulopathy in an infant with a vascular tumor. A retroperitoneal vascular tumor with an unusual combination of histopathological features is reported, and compared with vascular lesions described in the reported cases of Kasabach-Merritt syndrome in the literature. A large retroperitoneal tumor that had expanded through the sigmoid mesocolon into the sigmoid colon wall was resected from an 8-month-old infant with fully developed Kasabach-Merritt syndrome. Histological examination revealed a combination of venous (cavernous) malformation, kaposiform hemangioendothelioma and tufted angioma-like areas. Cellular tumor components (especially tufted angioma-like parts) infiltrated the wall of the sigmoid colon to the submucosal level. Immunohistochemical staining with antibodies to the Ki-67 antigen and proliferating cell nuclear antigen showed a low proliferative activity, whereas the antiapoptotic bcl-2 protein was expressed diffusely in tumor cells. This is the first reported case of a vascular tumor with tufted angioma-like elements found in the retroperitoneum, and the first reported in combination with kaposiform hemangioendothelioma and venous malformation in the same lesion. Considering the immunohistochemical results and overlapping histological features, it may be considered that tufted angioma and kaposiform hemangioendothelioma represent different growth patterns or stages in the development of a single type of hemangioma.

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We present a patient with acute lymphoblastic leukemia and ataxia-telangiectasia (A-T). The 4-year-old girl is the first child of young nonconsanguineous parents of Serbian origin. Gait problems appearing in the second year of life were treated by physiotherapy. At the age of 4 she was diagnosed with T-cell acute lymphoblastic leukemia and treated according to Berlin-Frankfurt-Munster strategy. Owing to typhlitis developing after 15 days of cytotoxic treatment, frequent radiologic examinations were performed causing profound aplasia. Typhlitis did not respond to conservative treatment but necessitated extensive bowel resection. At that time the A-T was suspected by our team and confirmed by increased chromosomal radiosensitivity and markedly reduced level of A-T mutated protein. Chemotherapy was continued without alkylating agents and further radiologic imaging ran an uncomplicated course. At present, the patient is in first remission and 2.5 years since the beginning of the treatment. We stress the importance of careful initial neurologic evaluation of children with malignancy.

Our study presents the results of ALL treatment from year 1995 to 2002 according to modified BFM protocol at the Department of Hematology of the University Children's Hospital, Belgrade. Modification was necessary due to inadequate drug and diagnostic reagent supply at that time and related mainly to reduced intensity of therapy and difference of definition of risk factors in relation to original BFM protocol. A total of 69 patients were treated, 36 girls (52.2%) and 33 boys (47.8%), mean age 4.5 years (range 0.4-16.8 yrs.). Thirteen children were classified as high risk, out of whom, one had Down syndrome, two had earlier corticosteroid treatment, nine were with T immunophenotype, out of whom three were poor prednisone responders and one was female infant. Clinical and laboratory parameters on diagnosis in our group were similar to the characteristics of patients in large published studies which exclude selection bias. There were four toxic deaths (5.8%) and ten relapses (14.5%). Five year event-free survival (EFS) with median follow-up of 5.2 years (range 2.2-9.2 years) was 70%.

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The authors describe a male infant with a history of transient pancytopenia who developed progressive bilateral proptosis associated with diffuse infiltration of the kidney and normal bone marrow. The histopathological examination of the kidney revealed diffuse infiltration of cells of myeloid origin with monocytic differentiation. Although orbital involvement by myeloid sarcoma, with or without concurrent acute myeloid leukemia, is well known, there are distinctive features in this patient that are not reported in the literature, namely bilateral proptosis and simultaneous presence of bilateral kidney infiltration, which enabled diagnosis.

Taking into consideration the uncertain long-term prognoses of these patients, follow-up and treatment is essential.