Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate.

High dose methotrexate (HD-Mtx) is highly effective and significantly improves overall acute lymphoblastic leukemia (ALL) patients survival. The pharmacodynamics of Mtx depends on the polymorphism of genes encoding proteins engaged in the folate metabolism pathway. The aim of the current study is to determine the relationship between variants of folate metabolism-related genes and the frequency of acute toxicities of HD-Mtx.

[Significance of L-asparaginase activity and biochemical parameters evaluation in children with acute lymphoblastic leukemia].

L-asparaginase is one of the most important agent used in multidrug chemotherapy regimens in the treatment of malignancies which derive from lymphoid system (acute lymhoblastic leukemias and non-hodgkin lymphoma). L-asparaginase leads to enzymatic cleavage of L-asparagine (amino acid essential for lymphoblasts' growth) to ammonia and L-aspartic acid, what results in depletion of L-asparagine in a serum and cerebrospinal fluid, and finally leads to destruction of lymphoblasts, which lack ability of endogenic L-asparagine production. In the course of L-asparaginase therapy severe side effects could be observed such as: coagulation disturbances, acute pancreatitis, anaphilactic shock and other types of allergic reaction, as well as liver and CNS failure.

[Minimal residual disease in childhood acute leukemias].

Monitoring of residual leukemic cells, so called minimal residual disease (MRD) in acute leukemias is of great importance in clinical practice. Especially evaluation of early response to treatment has a important prognostic value, and modifies the therapy schedule in a nowadays used treatment protocols. Methods used for monitoring of MRD consist of molecular techniques, which detect chromosomal aberrations or immunoglobulins and lymphocyte T receptor genes rearrangements, as well as method of flow cytometry, which detect immunophenotype typical for the leucemic clone.

[Acute lymphoblastic leukemia in children with initial leucocytosis above 50,000/mm3: summary of treatment results of Polish Pediatric Leukemia/Lymphoma Study Group].

Initial leucocytosis, presence of t(9;22) and t(4;11) translocations and poor response to therapy with steroids or induction chemotherapy are still included to poor risk factors group. From 1981 to 1986, children with acute lymphoblastic leukemia (ALL) and initial WBC above 50,000/mm3, achieved significantly worse treatment results than children with lower WBC: over 6-year disease-free survival were respectively 33% and 60%. In attempt to improve treatment results in children with hyperleucocytosis, modified American protocols called: New York (1987), New York I (1997), and New York II (1999) were introduced consecutively in the centers of Polish Pediatric Leukemia/ Lymphoma Study Group.

[Recommendation for using granulocyte and granulocyte-macrophage growth factor during anti-cancer therapy in children].

Neutropenia is the most often side effect during antineoplastic treatment. In this article current recommendations for clinical applications of granulocyte and granulocyto-macrophage hematopoietic factors and possibility of protection of neutropenia, and its serious complications in pediatric oncology are presented.

[Perspectives in the use of imatinib in the treatment of childhood cancers].

Introduction of novel diagnostic methods and multimodal therapy has resulted in about 70% probability of cure of childhood neoplasms. However, treatment results of some neoplastic diseases in children, including chronic myelogenous leukemia (CML) still remain unsatisfactory. The only chance of cure remains allogeneic hematopoietic stem cell transplantation, however availability of transplantation is still low as a limited number of donors is available.

[Advances in the treatment of children with high risk acute lymphoblastic leukemia (ALL) treated with modified "NEW YORK" protocols between 1987 and 2002].

From 1981 to 1986, in children with ALL and initial WBC > or = 50,000/mm3, over 6-year disease-free survival was significantly lower (33%) than in children with WBC < 50,000/mm3 (60%). In attempt to improve this unsatisfactory results, three modified American protocols named: "New York", "New York I", and "New York II", "New York I", and "New York II" were introduced consecutively in the centers of Polish Pediatric Leukemia Lymphoma Study Group (respectively, in 1987, 1997, and 1999). The treatment results achieved in three consecutive therapeutic groups of children with ALL and initial WBC > or = 50,000/mm3: group I--213 children (1987-1996), group II--58 children (1997-1999), and group III--52 children (1999-2001) are presented.