Alicja Chybicka

Publications of Alicja Chybicka

• Matched Sibling Versus Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Acquired Aplastic Anemia: Experience of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

  Authors: Dawid Szpecht, Ewa Gorczyńska, Krzysztof Kałwak, Joanna Owoc-Lempach, Marta Choma, Jan Styczyński, Jolanta Goździk, Agnieszka Dłużniewska, Mariusz Wysocki, Jerzy R Kowalczyk, Alicja Chybicka, Anna Pieczonka, Jacek Wachowiak

  Archivum immunologiae et therapiae experimentalis. 04/2012;

  In the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelatedIn the study, 48 children with severe acquired aplastic anemia (SAA) transplanted from matched sibling donor (MSD) between 1991 and 2009, and 38 children with SAA transplanted from matched unrelated donor (MUD) between 2000 and 2009 were evaluated. Engraftment was achieved in 45 (93.75 %) patients after MSD-hematopoietic stem cell transplantation (HSCT) and in 33 (86.8 %) after MUD-HSCT. Transplant-related mortality rate after MSD-HSCT was 8 %, while 37 % after MUD-HSCT. After MSD-HSCT 44 (91.7 %) patients are alive for 1-216 months (median: 85 months), while after MUD-HSCT 24 (63.2 %) patients for 1-84 months (median: 16 months). The 5-year probability of event-free survival after MSD-HSCT and MUD-HSCT was 87 and 53 %, respectively, while 5 years of overall survival was 91 and 64 %, respectively. It was concluded that MSD-HSCT as the first line treatment for children with SAA is a safe therapeutic approach with a low rate of treatment failures and excellent outcome. Results of MUD-HSCT in pediatric patients with SAA who failed to respond to immunosuppressive therapy are still inferior than those of MSD-HSCT. Treatment failures of MUD-HSCT are mainly related to infectious complications and graft failure. It seems, however, that HLA-matching of unrelated donors at allelic level along with early MUD-HSCT after FCA (FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin) conditioning, perhaps using lower Thymoglobulin dose could enable further improvement of long-term results in children with SAA who lack MSD.

• Long-term survival of a child with refractory anaplastic large cell lymphoma following therapy with an antisense oligonucleotide, topotecan, and vinblastine.

  Authors: Grazyna Wrobel, Radosław Chaber, Jolanta Rygier, Jolanta Bonar, Katarzyna Muszynska-Roslan, Alicja Chybicka

  Hematological oncology. 08/2011;

  Anaplastic large cell lymphoma includes a subset of highly aggressive tumours and has a relapse rate of 30% at 2 years. Relapsed patients often have poor clinical outcome. The use of antisenseAnaplastic large cell lymphoma includes a subset of highly aggressive tumours and has a relapse rate of 30% at 2 years. Relapsed patients often have poor clinical outcome. The use of antisense oligonucleotides to down-regulate Bcl-2 protein can reverse chemotherapy resistance. The authors describe an 11-year-old boy with recurrent anaplastic large cell lymphoma who had received double high-dose chemotherapy followed by autologous haematopoietic stem-cell transplantation, had refractory disease and then had achieved long-term remission with the use of an antisense oligonucleotides in combination with vinblastine and topotecan. Copyright © 2011 John Wiley & Sons, Ltd.

• [Assessment of lipid layer thickness of tear film in the diagnosis of dry-eye syndrome in children after the hematopoietic stem cell transplantation].

  Authors: Małgorzata Kurpińska, Ewa Gorczyńska, Joanna Owoc-Lempach, Aleksandra Bernacka, Marta Misiuk-Hojło, Alicja Chybicka

  Klinika oczna. 01/2011; 113(4-6):136-40.

  Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS) is recognized as the most frequent ocular complication after allogeneic stem cell transplantation (allo-SCT). KCS can appearDry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS) is recognized as the most frequent ocular complication after allogeneic stem cell transplantation (allo-SCT). KCS can appear either due to insufficient tear production or excessive tear evaporation, both resulting in tears hyperosmolarity that leads to ocular damage. The evaporation rate and better film stability is determined primarily by the status of the lipid layer. Observation and classification of tear film lipid layer interference patterns in normal and dry eyes in patients after allogeneic stem cell transplantation with a follow-up time of 6 months-5 years (median 26.54 months). Investigation of the relation between the lipid layer interference patterns in normal and dry eyes and the results of other dry eye examinations and complaints. Relation between DES and conditioning regimes, including total body irradiation and high-dose chemotherapy, immunosuppressive drugs, the time after allogeneic stem cell transplantation and chronic graft-versus-host disease. Precorneal tears lipid layer interference patterns, were examined in 114 eyes in treatment group with the Tearscope-plus. Patient with dry eye were identified on the basis of Schirmer test scores and/or tear breakup time, and positive lissamine and/or fluorescein staining. 42 of 114 eyes (36.8%) developed DES after allo-SCT A significant correlation between thickness of lipid layer and BUT, Schirmer test, lissamine green and fluorescein staining was found in the treatment group. A significant association was found between present chronic GVHD and DES in children. DES was not associated with TBI, corticosteroids, immunosuppressive drugs and the time in the present study. Tears lipid layer interference patterns are highly correlated with the diagnosis of DES. Tears lipid layer interference patterns ( noninvasive method), can be used to diagnose early DES in children after allo-SCT. Chronic GVHD play a major role in development of DES. dry eye syndrome, graft versus host disease, stem cell transplantation.

• Higher CD34(+) and CD3(+) cell doses in the graft promote long-term survival, and have no impact on the incidence of severe acute or chronic graft-versus-host disease after in vivo T cell-depleted unrelated donor hematopoietic stem cell transplantation in children.

  Authors: Krzysztof Kałwak, Julita Porwolik, Monika Mielcarek, Ewa Gorczyńska, Joanna Owoc-Lempach, Marek Ussowicz, Agnieszka Dyla, Jakub Musiał, Dominika Paździor, Dominik Turkiewicz, Alicja Chybicka

  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 04/2010; 16(10):1388-401.

  The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+)The aim of our study was to compare the results of unrelated donor (UD) peripheral blood stem cell transplantation versus UD bone marrow transplantation and to analyze the impact of infused CD34(+) and CD3(+) cell doses on survival and incidence of severe graft-versus-host disease (GVHD) in 187 children who underwent UD hematopoietic cell transplantation with the use of in vivo T cell depletion (antithymocyte globulin or CAMPATH-1H). HLA typing was performed at the "high-resolution" level. Patients receiving > or =10 x 10(6) CD34(+) cells/kg and > or =4 x 10(8) CD3(+) cells/kg had better overall and disease-free survival. Multivariate analysis has shown that both infused CD34(+) cell dose <10 x 10(6)/kg and CD3(+) cell dose <4 x 10(8)/kg were independent risk factors for mortality (relative risk [RR] 1.8 and 1.71, P = .009 and .016, respectively). Regarding disease-free survival, multivariate analysis has revealed another independent risk factor for poor outcome apart from the 2 earlier-mentioned cell doses, which was the use of donors mismatched at 2 HLA antigens or 3 HLA allele/antigens (RR 2.5, P = .004). In age groups 0-10 years and 10-20 years, CD34(+) cell doses higher than the age-adjusted median dose clearly favored survival. Higher infused doses of CD34(+) and CD3(+) cells did not result in an increased rate of severe GVHD. The use of mismatched donors was the only independent risk factor for the incidence of severe acute GVHD (RR 2.2, P = .046). The report demonstrates for the first time in a pediatric cohort, that higher doses of transplanted CD34(+) and CD3(+) cells lead to an improved survival without an increased risk of severe GVHD. The study findings may be limited to the population of patients receiving in vivo T cell depletion, which is now broadly used in unrelated donor setting in Europe.

• [Long-term observations of children with acute lymphoblastic leukemia and high leukocytosis treated according to modified "New York" protocols (1987-2003)].

  Authors: Kinga Kwiecińska, Walentyna Balwierz, Angelina Moryl-Bujakowska, Jacek Wachowiak, Katarzyna Derwich, Michał Matysiak, Katarzyna Pawelec, Alicja Chybicka, Grzegorz Dobaczewski, Jerzy R Kowalczyk, Hanna Wiśniewska-Slusarz, Danuta Sońta-Jakimczyk, Tomasz Szczepański, Renata Tomaszewska, Mariusz Wysocki, Jan Styczyński, Anna Balcerska, Anna Płoszyńska

  Przegla̧d lekarski. 01/2010; 67(6):350-4.

  Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Due to new therapeutic schedules and cooperation between oncological centers it is curable in more than 80% of affectedAcute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Due to new therapeutic schedules and cooperation between oncological centers it is curable in more than 80% of affected children. For the optimalization of the therapy there is necessary to assess the risk criteria that have influence on the treatment results in the certain groups of patients. Hyperleukocytosis and the age (less than 1 year and more than 10 years) are known as unfavorable risk factors. The study was designed to assess the long-term treatment results in children with ALL and the initial leukocytosis over 50 000/mm3 with the use of the modified "New York" protocols. We present the treatment results of 340 children with ALL treated in nine centers of Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) according to three consecutive versions of modified "New York" protocol (group I, II, and III) between 1987 and 2003. Within the analyzed groups the first complete remission (I CR) was achieved in 91%, 95% and 96% of the patients, respectively. Relapses occurred in 37%, 21.5% and 26% of the patients and 3.7%, 1.8% and 5.7% of children died in the I CR due to complications, in the I, II and III therapeutic group, respectively. Obtained 5-and 10-year event-free survival (EFS) were 56% and 53.5% for the group I and 73% and 73% for the group II. Five-year EFS for the group III was 67%. The implementation of the New York protocol in 1987 and New York I in 1997 has improved the treatment results in children with ALL and initial leukocytosis over 50 000/mm3. Protocol New York II did not further improve the treatment results. Among analyzed parameters (age, gender, the initial leukocytosis, the blast cells immunophenotype) only age had the statistical significance. The implementation of modified "New York" protocols has improved the treatment results in children with ALL and initial leukocytosis over 50 000/mm3 compared to previous results.

• [Treatment failure in children with acute myelocytic leukemia: over 25-year experience of Polish Pediatric Leukemia/Lymphoma Study Group with four consecutive unified treatment protocols for childhood acute myelocytic leukemia].

  Authors: Agnieszka Dłuzniewska, Walentyna Balwierz, Anna Balcerska, Alicja Chybicka, Elzbieta Kamieńska, Grazyna Karolczyk, Irena Karpińska-Derda, Maryna Krawczuk-Rybak, Jerzy R Kowalczyk, Danuta Lewandowska [......] Joanna Pohorecka, Barbara Sikorska-Fic, Grazyna Sobol, Danuta Sońta-Jakimczyk, Renata Tomaszewska, Tomasz Urasiński, Jacek Wachowiak, Maria Wieczorek, Beata Wójcik, Mariusz Wysocki

  Przegla̧d lekarski. 01/2010; 67(6):366-70.

  Four consecutive intensive unified regimens (BFM-AML-83, PGP-AML 94, PGP-AML 98 AML-BFM 2004 Interim) for acute myelocytic leukemia (AML) have been conducted by the Polish Pediatric Leukemia/LymphomaFour consecutive intensive unified regimens (BFM-AML-83, PGP-AML 94, PGP-AML 98 AML-BFM 2004 Interim) for acute myelocytic leukemia (AML) have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) since 1983. The last one, introduced four years ago is still active, and only preliminary result may be presented. There were 726 children with AML diagnosed (226, 102, 247 and 151 in the I, II , III and IV periods, respectively), and 603 of them were eligible for evaluation (208, 83, 195 and 117, respectively). Complete remission rates were: 71.4%, 67.5%, 81.4% and 87% in consecutive periods, respectively. Five-year overall survival (OS) and event-free survival (EFS) rates were: 33% and 32% for PGP-AML 83 regimen, 38% and 36% for PGP-AML 94 regimen, and 53% and 46% for PGP-AML 98 regimen, respectively. For AML-BFM Interim 2004 the 3-year OS and EFS were 57% and 57%, respectively. Despite continuous improvement of the treatment results, the number of failures have remained too high, but the pattern have changed in the following way: Early deaths (from diagnosis to 15 day of treatment) decreased only in the fourth period to 3%. "Aplasia deaths" (between day 15 and 42) decreased gradually from 16% in the first period to 1.5% and 2.2% in the third and in the fourth period, respectively. Deaths in remission decreased from 10% in first and second period to 3.5% at present. Number of non responders increased between first and second period from 6% to 18%, later decreased to 8.2% at present. These trends e.g. decrease of early death and treatment related mortality reflect both the better efficacy of antileukemic treatment and the improvement of supportive care.

• [Genotyping and minimal residual disease study in children with acute myeloid leukemia: preliminary results].

  Authors: Walentyna Balwierz, Jacek J Pietrzyk, Gracjan Wator, Karol Stozek, Tomasz Klekawka, Kinga Kwiecińska, Agnieszka Dłuzniewska, Michał Matysiak, Iwona Malinowska, Barbara Sikorska-Fic [......] Elzbieta Kamieńska, Grazyna Sobol, Maria Wieczorek, Grazyna Karolczyk, Mariusz Wysocki, Sylwia Kołtan, Jerzy R Kowalczyk, Beata Wójcik, Teofila Ksiazek, Katarzyna Szewczyk

  Przegla̧d lekarski. 01/2010; 67(6):371-4.

  The aim of the paper is to present the initial results of molecular examination which was started in 2006 for children with acute myeloid leukemia. Better knowledge of biology of this disease, canThe aim of the paper is to present the initial results of molecular examination which was started in 2006 for children with acute myeloid leukemia. Better knowledge of biology of this disease, can result in establishing of new risk factors what allows more precise patient stratification to different therapeutic groups. Study was obtained patients until to 18 years of age treated according to AML-BFM 2004 INTERIM protocol in 14 centers of the Polish Pediatric Leukemia/Lymphoma Study Group. Mononuclear cells were collected from bone marrow on time points established according to the AML-BFM 2004 INTERIM protocol. Collected cells were isolated on Ficoll gradient, and RNA and DNA were isolated using TRIZOL reagent. To synthesize cDNA an amount of 1 mg of total RNA was used. To perform quantitative RT-PCR and RQ-PCR reactions 4 fusion gene transcripts (AML1-ETO, CBFb-MYH11, PML-RARA /subtype bcrl and bcr3/) were used according to the protocol established by Europe Against Cancer Program. An expression of WT1 gene was tested additionally. An analysis of ABL control gene was used to normalize of achieved results. Determination of duplication of FLT3 gene in DNA sample was performed with starters complementary to JM region. Genotyping was performed in 75 patients with acute myeloid leukemia so far. AML1-ETO fusion gene transcript was found in 14 patients (19%). PML-RARA (subtype bcr3) and CBFB-MYH11 gene transcripts were detected in 3 (4%) and 3 (4%) patients, respectively. Duplication of FLT3 gene was found in 4 (5.3%) cases. Between 67 tested children over expression of WT1 was present in 51 patients (76%). Analysis of MRD level in subsequent time points showed systematic decrease of number of fusion gene transcript copies and gene WT1 expression. To establish the rate of molecular marker presence in AML in children and the influence of the presence of MRD on the treatment results as well, the study has to be conducted on a larger group of patients with longer follow-up.

• [Can children with Hodgkin's disease be treated with chemotherapy only?].

  Authors: Walentyna Balwierz, Tomasz Klekawka, Angelina Moryl-Bujakowska, Michał Matysiak, Barbara Sopyło, Jacek Wachowiak, Małgorzata Kaczmarek-Kanold, Danuta Sońta-Jakimczyk, Anna Janik-Moszant, Alicja Chybicka [......] Mariusz Wysocki, Andrzej Kołtan, Maryna Krawczuk-Rybak, Katarzyna Muszyńska-Rosłan, Wojciech Młynarski, Małgorzata Stolarska, Grazyna Sobol, Maria Wieczorek, Grazyna Karolczyk, Agnieszka Urbanek-Dadela

  Przegla̧d lekarski. 01/2010; 67(6):375-81.

  Currently over 90% of children and adolescents with Hodgkin's disease (HD) can be cured thanks to use of multidrug chemotherapy (CT) combined with involved-field radiotherapy (IF-RT). However, theCurrently over 90% of children and adolescents with Hodgkin's disease (HD) can be cured thanks to use of multidrug chemotherapy (CT) combined with involved-field radiotherapy (IF-RT). However, the intensive treatment may increase the risk of late complications which may impair the patients' quality of life. In order to decrease the incidence of late complications the protocol with limited use of IF-RT was introduced in centers of Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). This study presents the treatment results of patients treated with CT only in comparison with the therapy results of children treated with CT and IF-RT. From 1997 to 2006, 634 children (age: 2-22,5 years) with HD were treated in 14 oncological centers of PPLLSG. Majority of patients received CT (3-8 cycles of MVPP/B-DOPA) combined with IF-RT. In 45 patients with IA-IIA stages presenting favorable risk factors (small mediastinal tumor, peripheral nodular mass of a maximum diameter < 6 cm, involvement of less than three nodular regions, ESR < 50 mm after 1 h, histologic type other than lymphocyte depletion and very good treatment response assessed after 3 CT cycles) IF-RT was omitted. Among 634 children first complete remission (RC) was not achieved in 2.4% of patients. Relapses occurred in 24 children (3.9%). The rates of 5-year overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS) were 97%, 96% i 92%, respectively. All patients treated with CT only remain in first CR. All serious late complications (including 7 second neoplasms) occurred in patients treated with CT combined with RT. Seven children died because of severe complications, among them two in first CR (aplastic anemia, sepsis). Our results show that the use of CT only in precisely selected group of patients with HD do not impair the treatment results and may decrease the risk of late life threatening complications. Treatment response assessment with the use of PET may in future increase the number of patients treated without RT and limit the need of the use of invasive diagnostic methods in patients with residual mass.

• [Treatment results of children with neuroblastoma: report of Polish Pediatric Solid Tumor Group].

  Authors: Walentyna Balwierz, Aleksandra Wieczorek, Tomasz Klekawka, Katarzyna Garus, Katarzyna Bolek-Marzec, Danuta Perek, Ewa Swieszkowska, Wojciech Młynarski, Małgorzata Stolarska, Jerzy R Kowalczyk [......] Grazyna Sobol, Agnieszka Mizia-Malarz, Tomasz Urasiński, Jarosław Peregut-Pogorzelski, Danuta Sońta-Jakimczyk, Halina Bubała, Maria Wieczorek, Michał Matysiak, Barbara Sopyło, Wojciech Madziara

  Przegla̧d lekarski. 01/2010; 67(6):387-92.

  Approximately 60 children aged 0-18 years are diagnosed of NBL each year in Poland. About 60% of all patients suffering from NBL have a chance for durable cure. Unfortunately the prognosis forApproximately 60 children aged 0-18 years are diagnosed of NBL each year in Poland. About 60% of all patients suffering from NBL have a chance for durable cure. Unfortunately the prognosis for patients within the high-risk group accounting for more than 50% of all NBL patients remains poor despite the introduction of more intensive chemotherapy regimens with radical surgery procedures and megachemotherapy with subsequent stem cell transplantation. Only one third of patients in this group can be cured. To improve the treatment results of the high-risk patient group and to decrease the rate of therapy related side effects current European treatment protocols have been introduced systematically in Poland. In February 2009 information about 389 patients (age 0.1-16.5 years) diagnosed between 2001 and 2008 were obtained. Results of therapy of 319 patients who started treatment from 2001 to 2007 were analyzed. Between 104 infants and 215 children over 1 year of age, stage 4 of disease was found in 25% and 54.5%, respectively. In this period additionally to European treatment protocols, two another protocols were used. Satisfactory treatment results were obtained in 104 infants (5-year event free survival /EFS/=82.6%), irrespective of the type of treatment protocol. Over 5-year EFS for children over 1 year of age in 1, 2 and 3 stage of disease was: 100%, 86.3% and 64.5%, respectively. On the contrary, 107 patients with 4 stage of disease achieved the 5-year EFS of 27% only. Treatment results obtained in patients treated according to the European HR-NBL-1/ESIOP protocol were better than for patients treated according to other treatment protocols (5-year EFS: 31.1% and 16.4%, respectively), but difference between these groups was not significant. Between 2001 and 2007 data reporting increased to 81% from 19% noted earlier. Unfortunately, results of treatment for children over 1 year of age remain still unsatisfactory. That is why there is a need of improvement of modern, unified treatment realization as well as better data reporting. For realization of these aims adequate financial support is essential.

• c.1810C>T Polymorphism of NTRK1 Gene is associated with reduced Survival in Neuroblastoma Patients.

  Authors: Beata S Lipska, Elzbieta Drozynska, Paola Scaruffi, Gian Paolo Tonini, Ewa Izycka-Swieszewska, Szymon Zietkiewicz, Anna Balcerska, Danuta Perek, Alicja Chybicka, Wojciech Biernat, Janusz Limon

  BMC cancer. 12/2009; 9(1):436.

  ABSTRACT: BACKGROUND: TrkA (encoded by NTRK1 gene), the high-affinity tyrosine kinase receptor for neurotrophins, is involved in neural crest cell differentiation. Its expression has been reported toABSTRACT: BACKGROUND: TrkA (encoded by NTRK1 gene), the high-affinity tyrosine kinase receptor for neurotrophins, is involved in neural crest cell differentiation. Its expression has been reported to be associated with a favourable prognosis in neuroblastoma. Therefore, the entire coding sequence of NTRK1 gene has been analysed in order to identify mutations and/or polymorphisms which may alter TrkA receptor expression. METHODS: DNA was extracted from neuroblastomas of 55 Polish and 114 Italian patients and from peripheral blood leukocytes of 158 healthy controls. Denaturing High-Performance Liquid Chromatography (DHPLC) and Single-Strand Conformation Polymorphism (SSCP) analysis were used to screen for sequence variants. Genetic changes were confirmed by direct sequencing and correlated with biological and clinical data. RESULTS: Three previously reported and nine new single nucleotide polymorphisms were detected. c.1810C>T polymorphism present in 8.7% of cases was found to be an independent marker of disease recurrence (OR=13.3; p=0.009) associated with lower survival rates (HR=4.45 p=0.041). c.1810C>T polymorphism's unfavourable prognostic value was most significant in patients under 18 months of age with no MYCN amplification (HR=26; p=0.008). In-silico analysis of the c.1810C>T polymorphism suggests that the substitution of the corresponding amino acid residue within the conservative region of the tyrosine kinase domain might theoretically interfere with the functioning of the TrkA protein. CONCLUSIONS: NTRK1 c.1810C>T polymorphism appears to be a new independent prognostic factor of poor outcome in neuroblastoma, especially in children under 18 months of age with no MYCN amplification.

• Treosulfan-based conditioning regimen in a second matched unrelated peripheral blood stem cell transplantation for a pediatric patient with CGD and invasive aspergillosis, who experienced initial graft failure after RIC.

  Authors: Maja Klaudel-Dreszler, Krzysztof Kalwak, Magdalena Kurenko-Deptuch, Beata Wolska-Kusnierz, Edyta Heropolitanska-Pliszka, Barbara Pietrucha, Bożena Mikoluc, Ewa Gorczyńska, Marek Ussowicz, Alicja Chybicka, Ewa Bernatowska

  International journal of hematology. 10/2009;

  Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent bacterial and fungal infections. InvasiveChronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent bacterial and fungal infections. Invasive aspergillosis (IA) is the leading cause of mortality in patients with CGD. We report the case of a 3-year-old boy with CGD, who developed IA despite antifungal prophylaxis. His treatment consisted of a 10-month-long multi-drug antifungal therapy, together with surgery, but these did not cause any substantial clinical improvement. BMT in high-risk patients with CGD remains a challenge due to both, higher risk of graft rejection and inflammatory flare in the course of immune recovery. Our patient rejected the first matched unrelated donor (MUD) allograft after RIC regimen recommended by the EBMT Inborn Errors Working Party for high-risk patients. After treosulfan-based conditioning and second MUD peripheral blood stem cell transplantation both, full reconstitution of the granulocytic series and complete recovery from IA, were achieved.

• c.1810C>T Polymorphism of NTRK1 Gene is associated with reduced Survival in Neuroblastoma Patients

  Authors: Beata Lipska, Elżbieta Drożynska, Paola Scaruffi, Gian Tonini, Ewa Iżycka-Świeszewska, Szymon Ziętkiewicz, Anna Balcerska, Danuta Perek, Alicja Chybicka, Wojciech Biernat, Janusz Limon

  BMC Cancer. 01/2009;

  Abstract Background TrkA (encoded by NTRK1 gene), the high-affinity tyrosine kinase receptor for neurotrophins, is involved in neural crest cell differentiation. Its expression has been reported toAbstract Background TrkA (encoded by NTRK1 gene), the high-affinity tyrosine kinase receptor for neurotrophins, is involved in neural crest cell differentiation. Its expression has been reported to be associated with a favourable prognosis in neuroblastoma. Therefore, the entire coding sequence of NTRK1 gene has been analysed in order to identify mutations and/or polymorphisms which may alter TrkA receptor expression. Methods DNA was extracted from neuroblastomas of 55 Polish and 114 Italian patients and from peripheral blood leukocytes of 158 healthy controls. Denaturing High-Performance Liquid Chromatography (DHPLC) and Single-Strand Conformation Polymorphism (SSCP) analysis were used to screen for sequence variants. Genetic changes were confirmed by direct sequencing and correlated with biological and clinical data. Results Three previously reported and nine new single nucleotide polymorphisms were detected. c.1810C>T polymorphism present in 8.7% of cases was found to be an independent marker of disease recurrence (OR = 13.3; p = 0.009) associated with lower survival rates (HR = 4.45 p = 0.041). c.1810C>T polymorphism's unfavourable prognostic value was most significant in patients under 18 months of age with no MYCN amplification (HR = 26; p = 0.008). In-silico analysis of the c.1810C>T polymorphism suggests that the substitution of the corresponding amino acid residue within the conservative region of the tyrosine kinase domain might theoretically interfere with the functioning of the TrkA protein. Conclusions NTRK1 c.1810C>T polymorphism appears to be a new independent prognostic factor of poor outcome in neuroblastoma, especially in children under 18 months of age with no MYCN amplification.

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

  Authors: Jacek J Pietrzyk, Miroslaw Bik-Multanowski, Walentyna Balwierz, Szymon Skoczen, Dorota Wojcik, Alicja Chybicka, Barbara Sikorska-Fic, Michal Matysiak, Tomasz Szczepanski, Danuta Sonta-Jakimczyk, Anna Ploszynska, Anna Balcerska, Katarzyna Mycko, Jerzy Bodalski, Maryna Krawczuk-Rybak, Jerzy Kowalczyk, Andrzej Koltan, Grazyna Sobol, Katarzyna Derwich, Przemko Kwinta

  Pediatric blood & cancer. 12/2008;

  BACKGROUND: The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study was toBACKGROUND: 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. PROCEDURE: Genotyping for the presence of 7 genetic variants in 403 patients and analysis of death cases were performed. RESULTS: Thirty-one children died before reaching remission maintenance phase. Genetic analysis revealed in this group increased frequency of homozygosity for c.677C>T polymorphism of the MTHFR gene (26% vs. 8% in the survivors; OR 4.09; 95% CI 1.67-10; adjusted for multiple testing P = 0.028). CONCLUSION: Our data suggest that modification of anti-leukemic treatment should be considered in patients homozygous for c.677C>T polymorphism. Pediatr Blood Cancer (c) 2008 Wiley-Liss, Inc.

• Chronic metastatic neuroblastoma.

  Authors: Bernarda Kazanowska, Adam Reich, Michal Jelen, Alicja Chybicka

  Pediatric blood & cancer. 05/2008; 50(4):898-900.

  The diversity of neuroblastoma and its clinical course depends on histology, biology and clinical features. We report a male presenting at 4 months of age with an abdominal mass and multipleThe diversity of neuroblastoma and its clinical course depends on histology, biology and clinical features. We report a male presenting at 4 months of age with an abdominal mass and multiple subcutaneous nodules. The diagnosis was made by histological examination of a subcutaneous nodule and elevated urinary markers. The patient remained well during the subsequent 9 years. During that time no cytostatic treatment was given. Attempt to treat with cis-retinoic acid 10 years later did not result in any significant change of the clinical course. The patient has remained in good clinical condition for a 15-year observation period, having both progressing and regressing distant subcutaneous metastases. Skin nodules are the hallmarks of the indolent clinical course of the disease. We suggest the use of the "chronic neuroblastoma" as a term to describe patients with neuroblastoma showing indolent disease course over a very long period of time, but never achieving complete remission.

• [Megachemotherapy and autologous stem cell transplantation in children with ewing sarcoma - polish experience.]

  Authors: Katarzyna Drabko, Agnieszka Zaucha-Prażmo, Marta Choma, Beata Wójcik, Agnieszka Dyla, Dominika Paździor, Krzysztof Kałwak, Alicja Chybicka, Szymon Skoczeń, Jolanta Goździk, Jan Styczyński, Mariusz Wysocki, Jerzy Kowalczyk

  Medycyna wieku rozwojowego. 02/2008; XII(4 part 2):1069-1073.

  AIM: To present results of megachemotherapy and autologus hematopoietic stem cell transplantation in children with Ewing sarcoma in 4 Polish pediatric transplantation centres. MATERIAL AND METHODS:AIM: To present results of megachemotherapy and autologus hematopoietic stem cell transplantation in children with Ewing sarcoma in 4 Polish pediatric transplantation centres. MATERIAL AND METHODS: Between the years 1995-2007 autologous stem cell transplantation was performed in 54 patients (25 girls and 29 boys) with Ewing sarcoma. 26 patients were in complete remission before megachemotherapy, 23 were in partial remission, 3 patients had progression of the disease and the status of 2 patients was unknown. 41 children received busulfan 16mg/kg and melphalan 140 mg/m(2), 8 children carboplatin 1500 mg/m(2), VP-16 40 mg/kg, melfalan 160 mg/m(2) and 5 children other megachemotherapy protocols. RESULTS: Probability of survival of patients after transplantation, in complete remission is 0,79 with median 35 months of observation time. For patients after transplantation in partial remission probability of survival was 0,25 with median observation time of 14 months. Patients in progressive disease died 1,3 and 7 months after transplantation. 32 children are alive and 22 patients died, 21 of them due to disease progression. CONCLUSIONS: 1. Megachemotherapy and autologous hematopoietic stem cell transplantation is a safe therapy in patients with high risk Ewing sarcoma in complete remission. 2. Proportion of patients with sustained remission after transplantation in greater as compared to the published data related to high risk group without megachemotherapy. 3. According to our data megachemotherapy did not improve outcome in patients with partial remission of the disease.

• [Results of immunosupressive therapy in children with severe aplastic anaemia. Report of the polish paediatric haematology group.]

  Authors: Katarzyna Pawelec, Michał Matysiak, Edyta Niewiadomska, Roma Rokicka-Milewska, Jerzy Kowalczyk, Jolanta Stefaniak, Walentyna Balwierz, Ewa Załęcka-Czerpko, Alicja Chybicka, Krzysztof Szmyd [......] Jacek Wachowiak, Grzegorz Grund, Wojciech Młynarski, Monika Bulas, Maryna Krawczuk-Rybak, Elżbieta Leszczyńska, Tomasz Urasiński, Jarosław Peregud-Pogorzelski, Anna Balcerska, Marek Włazłowski

  Medycyna wieku rozwojowego. 02/2008; XII(4 part 2):1092-1097.

  INTRODUCTION: Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When there is no donor available, combinedINTRODUCTION: Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When there is no donor available, combined immunosuppressive therapy is given. AIM: evaluation of results of immunosupressive therapy in children with severe aplastic anaemia. Material and methods: SAA was diagnosed in 105 children (42 girls, 73 boys), aged 2-18 years, in the eleven haematological centres in Poland, between 1993-2007. All patients received the Severe Aplastic Anaemia Working Party of the EBMT protocol which included: antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone. Granulocyto- or granulocytomacrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84 or 112 and 180 of the therapy. RESULTS: complete remission occurred in 53 patients (51.5%), partial remission in 27 (24.7%), no response was obtained in 25 children (23.8%) on day 180, of the therapy. Period of observation was from 12 months to 12.5 years. During this time relapse occurred in 10 patients (9.5%). We observed 22 deaths: 8 early, during the first 3 months of IS and 14 after the first 3 months of immunosuppresive therapy (IS). At present 70 children (66.6%) are in first remission with lasts from 12 months to 12.5 years. The survival at 12.5-years is 78.6%. During the 12.5 years of follow-up we had two cases with a late clonal complication (PNH and MDS). Transformation to acute nonlymphoblastic leukaemia was observed in two of our patients. CONCLUSIONS: 1. Immunosuppresive therapy (IS) in children with SAA, without bone marrow family donors, is more effective after introduction of combined IS (12.5 years survival in this study was 80% for children with very severe aplastic anaemia (v SAA). 2. In our studies among the children followed up after IS therapy, there were: 1 case of periodic nocturnal haemoglobinuria (PNH), 1 case of myelodysplastic syndrome (MDS) and 2 cases of myeloid leukaemia (probability of incidence was 3.8%).

• [Treatment results in children with the standard risk acute lymphoblastic leukemia treated with high dose of methotrexate (5.0 g/m2). 11 years of the Polish Pediatric Leukemia/Lymphoma Study Group experience]

  Authors: Katarzyna Derwich, Jacek Wachowiaki, Małgorzata Kaczmarek-Kanoldi, Anna Balcerska, Walentyna Balwierz, Alicja Chybicka, Jerzy R Kowalczyk, Michał Matysiak, Teresa Jackowska, Danuta Sońta-Jakimczyk, Mariusz Wysocki, Lidia Chełmecka-Hanuszewicz, Magdalena Cwiklińska, Andrzej Kołtan, Iwona Malinowska, Teresa Odój, Anna Płoszyńska, Monika Steczowicz, Violeta Wojciechowska, Anna Wójtowicz

  Przegla̧d lekarski. 02/2006; 63(1):7-10.

  Since 01.07.1993 to 30.09.2004, 675 children with ALL-SR were diagnosed and treated according to the modified ALL-BFM 90 protocol. Subject to statistical analysis (Kaplan-Meier method) were thus 197Since 01.07.1993 to 30.09.2004, 675 children with ALL-SR were diagnosed and treated according to the modified ALL-BFM 90 protocol. Subject to statistical analysis (Kaplan-Meier method) were thus 197 children with ALL-SR treated with HD-MTX in a dose 5.0g/ m2. Among them, 21 patients failed to respond to therapy: 2 (1.0%) early deaths, 2 (1.0%) deaths during I complete remission, 16 (8.2%) relapses, 1 (0.5%) second neoplasm. Relapses occured: 12 (6.2%) in bone marrow, 2 (1.0%) in central nervous system, 1 (0.5%) in testicle and in 1 (0.5%) child combined relapse was observed. Probability rates for 11-year event free survival (EFS) was 0.80 (0.03). Application of high dose of methotrexate is safety and effective in prevention of relapses, especially meningeal and testicular involvement.

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

  Authors: Szymon Skoczeń, Walentyna Balwierz, Angelina Moryl-Bujakowska, Katarzyna Pawińska, Aleksandra Luszczyńska, Anna Balcerska, Anna Płoszyńska, Alicja Chybicka, Grzegorz Dobaczewski, Katarzyna Juszczak [......] Jerzy Kowalczyk, Hanna Wiśniewska-Slusarz, Michał Matysiak, Agnieszka Krauze, Katarzyna Pawelec, Danuta Sońta-Jakimczyk, Renata Tomaszewska, Mariusz Wysocki, Jan Styczyńskii, Violetta Swiatkiewicz

  Przegla̧d lekarski. 02/2006; 63(1):11-4.

  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 toInitial 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. Actually treatment results obtained with those protocols in three groups of patients: group I: 214 children (1987-1996), group II: 58 children (1997-1999), and group III: 77 children (1999-2001) are presented. The observation was completed in March 31, 2004. In evaluated groups the first complete remissions (CR) were achieved in 91%, 95%, and 96% of patients, respectively. Relapses occurred in 72 patients of group I (37%), in 12 patients of group II (21%), and in 13 patients of group III (18%). The 5-year overall survivals were: 62%, 79%, and 78% (p=0.05) respectively; 5 year event-free survivals (EFS) were: 52%, 74%, and 69% (p=0.01) respectively. A significant improvement in treatment results in second compared with first group was achieved. Treatment results obtained with New York II are comparable with results obtained with New York I. The analysis of treatment results achieved shows the improvement of the prognosis in children with ALL and initial WBC above 50 000/mm3 in comparison with patients treated before 1987. There is strong necessity of unification of risk group qualification criteria in childhood ALL in term of comparable estimation treatment results achieved in different centers all over the world.

• [Does the residual mediastinal mass have prognostic significance in children with Hodgkin's disease (HD)?]

  Authors: Tomasz Klekawka, Walentyna Balwierz, Angelina Moryl-Bujakowska, Helena Stanuch, Michał Matysiak, Roma Rokicka-Milewska, Barbara Sopyło, Beatrycze Kołakowska-Mrozowska, Katarzyna Krenke, Alicja Chybicka [......] Małgorzata Kaczmarek-Kanold, Jerzy Kowalczyk, Teresa Odój, Anna Balcerska, Elibieta Adamkiewicz-Drozyińska, Mariusz Wysocki, Andrzej Koltan, Maryna Krawczuk-Rybako, Katarzyna Muszyńska-Rosłan, Małgorzata Stolarska

  Przegla̧d lekarski. 02/2006; 63(1):21-4.

  Prognostic significance of residual mediastinal tumor mass in children treated for HD as well as the choice of the optimal management of these cases still remains unknown. In years 1994-2001 in 10Prognostic significance of residual mediastinal tumor mass in children treated for HD as well as the choice of the optimal management of these cases still remains unknown. In years 1994-2001 in 10 PPLLSG participating centers 480 children (age 2-19.7 years) were treated for HD (stages I-IV). In 338 cases initial mediastinal/lung hilus involvement was present. All patients with initial mediastinal/lung hilus involvement were treated with multidrug chemotherapy combined with involved field radiotherapy. In five cases remission was not achieved. Complete remission (CR) was achieved in 226 patients and uncertain complete remission (UCR) in 107 patients, in whom after completion of planned treatment residual changes in mediastinum/lung hilus were identified in radiological examinations. Twenty four children with persistent mediastinal tumor underwent thoracoscopy or thoracotomy. In only one case histopathological examination revealed the presence of neoplastic cells in mediastinal mass tissue, in 2 another cases cystic changes in mediastinum were present, in one case thymic tissue was identified, necrotic tissue was present in 20 cases. Among 107 children with residual mediastinal tumor and 226 patients with CR achieved, relapses occurred in 6 and 18 patients respectively. Over 5-year relapse-free survival was 92.4% and 91.3% respectively. Patients with the presence of mediastinal/lung hilus tumor after the completion of the treatment do not have an increased risk of relapse, but before the completion of therapy they require careful, clear-sighted and repeated examinations including computed tomography (CT), magnetic resonance imaging (MRI) and especially positron emission tomography (PET) to evaluate the nature of persistent lesions. Only in clinically and radiologically doubtful cases tumor biopsy with subsequent histopatological examination should be performed.

• [The health state evaluation in persons after therapy of Hodgkin's disease in childhood: report of the Polish Pediatric Leukemia/Lymphoma Study Group]

  Authors: Walentyna Balwierz, Angelina Moryl-Bujakowska, Małgorzata Kaczmarek-Kanold, Jacek Wachowiak, Michał Matysiak, Barbara Sopyło, Elzbieta Stańczak, Danuta Sońta-Jakimczyk, Anna Janik-Moszant, Alicja Chybicka [......] Jerzy R Kowalczyk, Teresa Odój, Anna Balcerska, Teresa Stachowicz-Stencel, Mariusz Wysocki, Andrzej Kołtan, Sylwia Kołtan, Maryna Krawczuk-Rybak, Katarzyna Muszyńska-Rosłan, Grzegorz Zuj

  Przegla̧d lekarski. 02/2006; 63(1):25-8.

  The introduction of modern methods of combined therapy: chemotherapy and radiotherapy, allows the cure more than 90% of children and adolescents with Hodgkin's disease. However, the intensiveThe introduction of modern methods of combined therapy: chemotherapy and radiotherapy, allows the cure more than 90% of children and adolescents with Hodgkin's disease. However, the intensive treatment may cause early and late complications. The late complications may include: damage of soft tissues and respiratory, cardiovascular, skeletal, and endocrine systems, and second cancers. Late complications may impair the patients' quality of life after cessation of therapy. This study presents evaluation of health status of persons who underwent therapy for pediatric Hodgkin's disease in centers of Polish Pediatric Leukemia/Lymphoma Study Group. The special questionnaire was established to collect data concerning hematopoietic system function, damage of soft tissues and skeletal system, thyroid and reproductive organs function, respiratory, cardiovascular, and nervous system function, liver and kidney function, status of dentition, occurrence of infections, immunologic system function, and psychological and social problems. The project included patients treated in 9 pediatric oncology centers. During the study the questionnaires of 288 patients [151 boys (52.4%) and 137 girls (47.6%)] in whom treatment of Hodgkins's disease started in 1994-1996 (44 questionnaires), and in 1997-2001 (244 questionnaires). In 42 patients no diagnostic procedures were performed. In this group 20 patients are currently under care of adult oncology clinics, 21 failed to come for a visit, and one patient is treated because of HD progression. The questionnaires of 246 patients treated in 1994-1996 (25 questionnaires) and 1997-2001 (221 questionnaires), were analyzed and the data on the late complications of these patients were obtained. General health status of examined patients was found satisfactory. However, 2.3% of patients had radiological evidence of pulmonary fibrosis, and 4.9% had various ECG abnormalities. Endocrine therapy is needed in 4.5% of patients because of thyroid function abnormalities. Second cancers were diagnosed in 1.7% of patients. The health status of children and adolescents cured from Hodgkin's disease and other childhood cancers should be regularly evaluated. Results of these evaluations will be the basis for introducing new treatment protocols aimed of decreasing the incidence of late complications while maintaining or improving cure rates.