Grazyna Sobol

Additional genetic risk factor for death in children with acute lymphoblastic leukemia: A common polymorphism of the MTHFR gene

The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study was to evaluate the role of selected polymorphisms of genes associated with metabolism of chemotherapeutic drugs as prognostic markers in children with acute lymphoblastic leukemia.

Polymorphism of the thymidylate synthase gene and risk of relapse in childhood ALL

Polymorphisms of genes encoding proteins involved in drug metabolism can influence the efficacy of leukemia treatment. In this population-wide study we aimed to evaluate selected, metabolically active genetic polymorphisms as prognostic markers of treatment efficacy in acute lymphoblastic leukemia (ALL). A total of 51 cases of leukemia relapse were diagnosed in a group of 354 patients with ALL. A strong association between promoter tandem repeat polymorphism of the thymidylate synthase gene and the relapse frequency was found. We believe that genotyping for this variant should be performed in patients treated for ALL to enable further optimizing of treatment protocols.

Validation of a multi‐modal treatment protocol for Ewing sarcoma—A report from the polish pediatric oncology group

Ewing sarcoma (ES) is the second most common paediatric malignant bone tumor. Advances in multi‐disciplinary care have resulted in significant improvement in cure rates over the last decades. However, the generalization of those results in countries traditionally excluded from large cooperative trials has yet to be demonstrated. We report the results of modern multi‐disciplinary care for patients with ES in Poland.

Prognostic value of proangiogenic cytokines in children with lymphomas

Angiogenesis and proangiogenic cytokines are involved in neoplastic development. The role of these processes in lymphoma formation has not been established. The aim of the study was to assess angiogenesis on the basis of serum levels of vascular‐endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in childhood lymphomas. The prognostic value of these parameters was determined in the examined children.

Cervical Ectopic Thymus in a 9-month-old Girl—diagnostic Difficulties

Ectopic cervical location of the thymus is a very rarely diagnosed developmental disorder in children. This anomaly is usually manifested clinically as a neck tumor suggesting lymphadenopathy, which is also differentiated from more frequently occurring cervical cysts, angiomas, or malignant neoplasms. A decisive examination is the histopathologic assessment of the tumor, supported by necessary immunoassays. A diagnostic process is sometimes very difficult and the results are ambiguous; what is more, this process has a decisive impact on the childs future life. Therefore, a histopathologic evaluation performed by 2 independent pathologists should become the standard procedure. We present the case of a 9-month-old girl, in whom, after a difficult diagnostic process, ectopic cervical location of the thymus was diagnosed.

Outcome of refractory and relapsed acute myeloid leukemia in children treated during 2005–2011 – experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)

Aim of the study Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005–2011. Material and methods The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. Results Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. Conclusions The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.

Individualized tumor response testing profile has a prognostic value in childhood acute leukemias: multicenter non-interventional long-term follow-up study

Abstract A total number of 817 children with acute lymphoblastic leukemia (ALL) and 181 with acute myeloblastic leukemia (AML) were assessed for individualized tumor response testing (ITRT) profile as a prognostic factor in long-term follow-up. For each patient, ITRT, initial response to therapy and long-term outcome were assessed. In initial ALL, an impact on long-term response was shown in ITRT for 13 drugs, while in initial AML only for cytarabine. For patients with ALL, a combined five-drug ITRT profile for prednisolone, l-asparaginase, vincristine, cytarabine and daunorubicin or doxorubicin had predictive value for probability of disease-free survival (pDFS) in univariate analysis, whereas in multivariate analysis, bone marrow response by day 33 was the only prognostic factor. For patients with AML, no factor had prognostic value for pDFS in univariate analysis, while ITRT to cytarabine almost reached significance. In conclusion, ITRT can possibly be regarded as a risk factor in childhood acute leukemias.

Micafungin in invasive fungal infections in children with acute leukemia or undergoing stem cell transplantation

Jan Styczynski, Krzysztof Czyzewski, Mariusz Wysocki, Olga Zajac-Spychala, Jacek Wachowiak, Tomasz Ociepa, Tomasz Urasinski, Olga Gryniewicz-Kwiatkowska, Agnieszka Kolodziejczyk-Gietka, Bozenna Dembowska-Baginska, Danuta Perek, Malgorzata Salamonowicz, Lukasz Hutnik, Michal Matysiak, Karolina Siewiera, Jowita Frackiewicz, Krzysztof Kalwak, Wanda Badowska, Zofia Malas, Jolanta Gozdzik, Agnieszka Urbanek-Dadela, Graz_yna Karolczyk, Weronika Stolpa, Grazyna Sobol, Zuzanna Gamrot, Mariola Woszczyk and Lidia Gil Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland; Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland; Department of Pediatric Hematology and Oncology, Pomeranian Medical University, Szczecin, Poland; Department of Oncology, Children’s Memorial Health Institute, Warszawa, Poland; Department of Pediatric Hematology and Oncology, Medical University, Warszawa, Poland; Department of Pediatric Stem Cell Transplantation, Hematology and Oncology, Medical University, Wroclaw, Poland; Division of Pediatric Hematology and Oncology, Children Hospital, Olsztyn, Poland; Department of Clinical Immunology and Transplantology, Stem Cell Transplant Center, University Children’s Hospital, Jagiellonian University Collegium Medicum, Krakow, Poland; Division of Pediatric Hematology and Oncology, Children Hospital, Kielce, Poland; Department of Pediatric, Division of Pediatric Oncology, Hematology and Chemotherapy, Silesian Medical University, Katowice, Poland; Division of Paediatric Haematology and Oncology, Chorzow Paediatric and Oncology Center, Chorzow, Poland; Department of Hematology, University of Medical Sciences, Poznan, Poland

Rhabdomyolysis: rare complications with a difficult prognosis in the course of anticancer treatment.

Rhabdomyolysis refers to a number of clinical and biochemical symptoms, which result from the destruction of skeletal muscles. The following triad of symptoms is considered typical: myalgia, muscle weakness, and dark urine. The most common reasons for rhabdomyolysis in children are infections. It has also been reported that rhabdomyolysis may be caused by chemotherapy drugs. The most difficult complication of rhabdomyolysis is renal failure. The authors present a 17-year-old boy diagnosed with Ewing sarcoma and a 16-year-old boy suffering from acute leukemia, both with rhabdomyolysis developed in the course of infection caused by Clostridium difficile, and drug-induced neutropenia.

Serum concentrations of proangiogenic cytokines (VEGF, bFGF) depending on the histopathological types of Hodgkin lymphoma in children – preliminary report

Summary Background The different histological types of classical Hodgkin Lymphoma (cHL) differ from other percentage share of the Reed-Sternberg cells (R-SC) in the affected lymphoid tissue In the Lymphocyte Depletion cHL (LDcHL) type are present almost only R-SC. In turn, in the Nodular Lymphocyte Predominant Hodgkin lymphoma (NLP-HL) in the structure lymphocytes, histiocytes ora “popcorn” cells are present. Angiogenesis, which is necessary for development neoplasma tissue, is stimulated by proangiogenic cytokines including Vascular-Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF). In HL these cytokines are produced mainly by the R-SC. The aim of the study was to assess the concentrations of VEGF and bFGF in the serum (sVEGF, sbFGF) in different histopathological types childhood HL. Procedure 37 children with HL were studied: group A – 34 children with CHL and group B – 3 children with NCHL. In the control group there were 20 children. Using enzyme-linked immunosorbent assays we quantified VEGF and bFGF in the serum of the children with HL. Results The median sVEGF in group A was 657.137 pg/ml (43.777–1210.52) and was significantly higher (p Conclusions Conclusions. sVEGF in children with cHL are significantly higher in relation to the NLP-HL at the moment of diagnosis. There is a tendency to different sVEGF in the histopathological types of CHL.