Papers by Mariusz Wysocki
Cancers
Background: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (A... more Background: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML). Methods: The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983–1993, n = 187), AML-PPGLBC 94 (1994–1997, n = 74), AML-PPGLBC 98 (1998–2004, n = 151), AML-BFM 2004 Interim (2004–2015, n = 356), and AML-BFM 2012 (2015–2019, n = 131). Results: The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05; event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05; and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reducti...
Blood
Background: The beginnings of pediatric oncology in Bydgoszcz, Poland dates back to the year 1958... more Background: The beginnings of pediatric oncology in Bydgoszcz, Poland dates back to the year 1958. The first patient was treated with prednisolone only. Objective: Analysis of results of childhood acute lymphoblastic leukemia therapy in Bydgoszcz region in 1958–2008. Patients and methods: A total number of 570 children were diagnosed and treated over the period of 50 years, including: 215 children treated with different drugs and combinations in 1958–1972, 49 children treated with Memphis V–VII protocols in 1976–1983, 114 children treated with ALL-BFM83 or ALL-BFM86 protocols in 1983– 1995 and 192 children treated with ALL-BFM90, New York I–II or ALL-IC-2002 between 1995–2008. Results: A number of patients with „events” in respective time periods was: 205/215 (95.3%, in 1958–1972); 44/49 (89.8%, in 1976–1983), 54/114 (47.4%, in 1983–1995), 56/192 (29.2%, in 1995–2008). The values of 5-year pEFS in consecutive therapeutic periods were: p=0.012±0.008 (1958–1972), p=0.102±0.043 (in 197...
Blood
4220 Bone marrow transplantation (BMT) is a therapy of choice in children with severe aplastic an... more 4220 Bone marrow transplantation (BMT) is a therapy of choice in children with severe aplastic anemia (SAA), but it is possible only in about 15-20% patients who have family donors, so the majority of them received the immunosuppressive therapy (IST). We want to present the results of IST obtained in 116 children treated between 1993-2008 years at 11 pediatric hematology centers of the Polish Pediatric Hematology Group (PPHG),, 55 patients (22 girls and 33 boys aged 0,6-17,5 years) received antithymocyte rabbit globulin (ATG) as a first course of therapy. ATG was administered according to PPHG and Working Party SAA Group of EBMT protocol: ATG 3.75mg/kg iv for 5 days, cyclosporin A (CSA) 5mg/kg orally from day 1 to day 180 and granulocyte-stimulating factor during deep neutropenia. Remission of the disease was assessed on days 112, 180 and 360 from start of therapy on the basis of blood and bone marrow examination. The results on 112 and 180 were similar. The remission was achieved i...
Blood
3435 Objective: One of the main patophysiological mechanism of aplastic anemia (AA) is immune-med... more 3435 Objective: One of the main patophysiological mechanism of aplastic anemia (AA) is immune-mediated destruction of hematopoietic cells. In children with severe acquired aplastic anemia (SAA) allogenic bone marrow transplantation is the first choice. If there is no matched sibling donor the first line of treatment is immunosuppressive therapy (IST) which consists of ATG combined with cyclosporine A. Aim. The aim of this study was to analyze the results of IST containing rabbit anti-thymocyte globulin (r-ATG) performed on children with SAA and vSAA treated between 1996–2009 yr. We wanted to assess the influence of such factors as response to treatment, etiology, sex, age, type of AA, for: event free survival (EFS), and progression free survival (PFS) We analyzed deaths rate, relapses rate, clonality and side effects of IST. Materials and methods. We retrospectively analyzed group of 55 children with SAA and vSAA. The group consisted of 23 girls and 32 boys, the median age was 10 ye...
Frontiers in Oncology
Background: Amplification of the MYCN oncogene is the most unfavorable genetic factor in neurobla... more Background: Amplification of the MYCN oncogene is the most unfavorable genetic factor in neuroblastoma patients. However, knowledge about the clinical impact of low-level multiplication of MYCN is still insufficient. Therefore, we aimed to investigate the disease course in patients with different copy number status of MYCN. Materials and Methods: We examined 105 children diagnosed with neuroblastoma from 2010 to 2018 in five pediatric oncology centers in Poland. We determined the MYCN status at diagnosis by the interphase FISH examination and assessed the clinical outcome in patients. Results: A total of 35% of tumors presented with chromosome 2 numerical changes, 20% had MYCN amplification and 16% revealed 2p gain. Unexpectedly, we observed very low overall survival and event free survival (EFS) rates in neuroblastomas with 2p gain, which were comparable with patients with MYCN amplification. Conclusions: The 2p gain alteration should be reported as a strong unfavorable prognostic marker in neuroblastoma patients.
Annals of Hematology
Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fun... more Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter crosssectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs Krzysztof Czyżewski and Jan Styczyński contributed equally to this work.
Journal of Pediatric Hematology/Oncology
Enterobacterales represent a serious threat to transplant patients due to their increase frequenc... more Enterobacterales represent a serious threat to transplant patients due to their increase frequency of carbapenem resistance and wide spreading. We present a case of an infant with acute lymphoblastic leukemia undergoing hematopoietic stem cell transplantation. Before transplantation an unusual double colonization of the gastrointestinal tract with extremely resistant Escherichia coli and Klebsiella pneumoniae strains producing metallo-beta-lactamase was diagnosed. Respective epidemiological management was implemented, based on the strict reverse isolation in patient-protective environment, and intensified antimicrobial surveillance. After granulocyte recovery, no extremely drug-resistant strains were found, and no case of isolation and/or transmission of carbapenem-resistant bacteria has been identified in the transplant center during the following 6 months.
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2018
The purpose of the survey was to evaluate the development and current use of hematopoietic stem c... more The purpose of the survey was to evaluate the development and current use of hematopoietic stem cell transplantation (HSCT) in Poland between 1989-2016. The data for analysis (indication, number of performed HSCT, HSCT type, donor type, and stem cell source, year) have been collected annually using a standardized form. In Poland, between 1989-2016, the number of pediatric transplant beds grew from one to 40 and number and rate of transplants increased annually from 1/year (0.8/10 million) to 186/year (248/10 million). During the analyzed time period 2506 HSCTs were performed, including 1718 (68.6%) allogeneic transplants (allo-HSCT) with142 in 2016 and 788 (31.4%) autologous transplants (auto-HSCT) with 44 in 2016. Among 1718 allo-HSCT, 74% were performed for malignancy (ALL 47.2%, AML 26.2%, MDS 10.8%, CML 8.1%, NHL/HD 6.1%, others 2.5%), and 26% for non-malignant disorders (SAA 41%, congenital immunodeficiencies 35.4%, hereditary bone marrow failure 16%, metabolic disorders 7%). A...
Leukemia & Lymphoma
The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial... more The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.
Anticancer Research
Immune recovery is a key factor in the management of patients after allogeneic hematopoietic stem... more Immune recovery is a key factor in the management of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study analyzed the factors contributing to immune reconstitution after allo-HSCT. Overall, 65 children with malignant or non-malignant diseases were included in multivariate analyses. The following factors contributed to a faster immune recovery: peripheral blood as a stem cell source and reactivation of CMV infection for CD3 and CD4 lymphocyte subpopulations; reactivation of CMV infection for CD8 subset; donor EBV-IgG and no EBV reactivation for CD19 lymphocytes; recipient age below 10 years and peripheral blood as a stem cell source for NK cells. For CD2 and CD4/CD8 ratio no factor was significant in multivariate analysis. Patients receiving a graft from an EBV-IgG-positive donor and not having early EBV post-transplant viremia show faster recovery of the B-cells, while patients with early CMV-DNA-emia have a better re-establishment of T-cell subsets.
Postepy dermatologii i alergologii, 2018
Toll-like receptor 7 (TLR7) is an important molecule involved in the development of autoimmunity ... more Toll-like receptor 7 (TLR7) is an important molecule involved in the development of autoimmunity and the response to different pathogens. Several polymorphisms within the gene were previously found to be associated with systemic lupus erythematosus (SLE). However, none of those studies investigated the promoter flanking variants rs1634318 and rs1616583. gene diversity has not been analyzed with respect to discoid lupus erythematosus (DLE) development, while its role in the human immunological response to fungal infection is not fully known. To clarify the potential involvement of two novel single-nucleotide polymorphisms (SNPs) located in the gene (rs1634318 and rs1616583) in a variety of immune-related conditions, we studied the variability of these loci in patients from a Polish population with SLE and DLE, as well as in immunocompromised patients who were affected by invasive aspergillosis (IA) and those who were not affected. Real-time polymerase chain reaction was used to genot...
Polish journal of pathology : official journal of the Polish Society of Pathologists, 2017
This study aimed to find novel genetic variants of susceptibility to aspąergillosis in paediatric... more This study aimed to find novel genetic variants of susceptibility to aspąergillosis in paediatric patients with haematological malignancies. Complete sequences of fifteen genes of human innate immunity (CCL2, CCR2, CD209, CLEC6A, CLEC7A and ten TLR genes) were studied in 40 patients diagnosed with haematological disorders (20 unaffected and 20 affected by aspergillosis). All samples were sequenced with MiSeq (Illumina) and 454 (Roche Diagnostics) technologies. Statistical significance of the differences between studied groups was determined using the two-tailed Fisher's exact test. Sixty variants of potential importance were identified, the vast majority of which are located in non-coding parts of the targeted genes. At the threshold of p < 0.000005, one intergenic (TLR2 rs4585282) and one intronic variant (CLEC6A rs12099687) were found significant between the case and control groups for genotype and allele frequencies, respectively. Rs12099687 in CLEC6A was predicted to cons...
Pediatric hematology and oncology, Jan 17, 2017
Children with Down syndrome (DS) have a 20-fold increased risk of developing leukemia compared wi... more Children with Down syndrome (DS) have a 20-fold increased risk of developing leukemia compared with the general population. The aim of the study was to analyze the outcome of patients diagnosed with Down syndrome and acute lymphoblastic leukemia (ALL) in Poland between the years 2003 and 2010. A total of 1848 children were diagnosed with ALL (810 females and 1038 males). Of those, 41 (2.2%) had DS. The children were classified into three risk groups: a standard-risk group-14 patients, an intermediate-risk group-24, a high-risk group-3. All patients were treated according to ALLIC 2002 protocol. The median observation time of all patients was 6.1 years, and in patients with DS 5.3 years. Five-year overall survival (OS) was the same in all patients (86% vs 86%, long-rank test, p = .9). The relapse-free survival (RFS) was calculated as 73% in patients with DS and 81% in patients without DS during a median observation time (long-rank test, p = .3). No statistically significant differenc...
Wiadomości Lekarskie, 2003
Przegla̧d Lekarski, Feb 1, 2004
Germ cell tumors constitute about 3% of all pediatric malignancies. Since 1998 the multicenter tr... more Germ cell tumors constitute about 3% of all pediatric malignancies. Since 1998 the multicenter trial was initiated in Poland. 95 children (aged from 1 month to 17 years--mean 9.2 years) were registered. There were 38 boys and 57 girls. Diagnosis was made on histopathological examination in 88% patients (pts) and in 12% was established on imaging and biochemical findings (elevated AFP). Mixed germ cell tumor and yolk sac tumor prevelaged. AFP was elevated in 72% pts; in 26% it was over 15.000. Primary tumor was localized in gonads (59%) and in sacrococcygeal region (30%). Following disease stages were identified: I and II--41% pts, III--34%, IV--25%. All patients were treated according to French TGM&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;95 protocol. 43 belonged to high risk and 52 to standard risk group. 77 children completed therapy, 15 continue treatment and 3 were lost from follow-up. Among children who were off therapy, 70 (91%) are alive in a complete remission (second remission in 3 cases). Survival in high risk group is 89%, while in standard risk group is 93%. Median time of follow-up is 31 months from the beginning of treatment and 25 months after completion of therapy. 7 children died; all had progressive disease. The outcome of malignant germ cell tumors treatment in Poland is favourable and comparable to results showed by other study groups in the world.
Anticancer Research, May 1, 2005
Background: Glucocorticoids are the most important group of drugs used in the treatment of childh... more Background: Glucocorticoids are the most important group of drugs used in the treatment of childhood acute lymphoblastic leukemia (ALL), however, resistance to this group remains the main obstacle in curing the disease. One of the possibilities to circumvent glucocorticoid resistance is the use of new compounds, such as cortivazol (CVZ), which has two binding sites for the glucocorticoid receptor. Aim: Analysis of ex vivo sensitivity to cortivazol and other glucocorticoids in childhood acute lymphoblastic leukemia, as well as the relationship to anticancer therapy outcome. Patients and Methods: Leukemic samples from 60 children with ALL were tested by the MTT assay for glucocorticoid resistance. Cell cycle before and after ex vivo glucocorticoid treatment was analyzed by flow cytometry. Results: Although all tested glucocorticoids presented significant crossresistance, CVZ showed high antileukemic activity. The equivalent activity of CVZ was 165-fold higher than prednisolone, 7.5-fold higher than dexamethasone and 2.8-fold higher than betamethasone. CVZ showed relatively better cytotoxicity than other glucocorticoids in prednisolone-poor-responders. CVZ, like other glucocorticoids, caused cell cycle arrest in the G1-phase, and increased the percentage of apoptotic cells to a greater extent than other glucocorticoids. The results of antileukemic therapy were strongly related to the ex vivo resistance to all tested glucocorticoids. Conclusion: Cortivazol has potent antileukemic activity in childhood ALL. Its activity is related to cell cycle arrest and induction of apoptosis.
Medical Science Monitor, Jul 1, 1997
The study describes the case of a male infant with giant hemangioma (localised on the head, neck ... more The study describes the case of a male infant with giant hemangioma (localised on the head, neck and upper part of thorax) with highly progressive, life-threatening symptoms of disseminated intravascular coagulation and superior vena cava syndrome. Due to lack of ...
Anticancer Research, Dec 1, 2012
The analysis of the prognostic impact of residual disease at day 15 of induction therapy, individ... more The analysis of the prognostic impact of residual disease at day 15 of induction therapy, individual tumor response testing (ITRT) at diagnosis, initial factors and initial therapy response to the risk of relapse in children with precursor B-cell acute lymphoblastic leukemia (ALL). A total of 87 children were tested at diagnosis for ITRT and for persistence of blasts in bone marrow at day 15 (BML15&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.5%) and were followed-up in long-term analysis. The probability of disease-free survival (pDFS) was significantly better for patients with an ITRT profile showing sensitivity to prednisolone, vincristine, daunorubicin, and L-asparaginase. Patients with BML15&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.5% had higher ITRT for prednisolone, daunorubicin, L-asparaginase, and etoposide. Three factors had predictive impact for relapse: BML15&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.5%, ITRT for prednisolone and high combined ITRT profile for prednisolone, vincristine and L-asparaginase (PVA score). Persistence of blasts in bone marrow at day 15, ITRT showing resistance to prednisolone and high PVA score were the strongest and comparable prognostic factors predicting relapse in childhood ALL.
Medycyna Wieku Rozwojowego, 2006
Approximately 2% of of all malignant tumours in boys are localised in the testis. Among them 80% ... more Approximately 2% of of all malignant tumours in boys are localised in the testis. Among them 80% are germ cell tumours with the malignant elements of yolk sac tumour. AIM of the study was evaluation of the efficacy of malignant testicular tumour treatment programme in children. Since 1998 31 boys aged 1 month to 18 years (median 14 years) with malignant testicular tumours were enrolled in the multicentre trial. Patomorphologically clear yolk sac tumour (33%) and mixed germ cell tumour (42%) with the majority of yolk sac tumour component or carcinoma embryonale, occurred most often. Alfa-feto-protein was increased in 63% and choriogonadotropin in 26 patients. 61% patients had local clinical stage and the tumour was localized in the testis. In 39% patients tumour exceeded the testis margin. 4 patients were excluded from analysis as 3 are actually treated and 1 died on the second day of admittance to hospital. All patients received TGM 95 regimen (Tumeurs Germinales Malignes). Surgery (orchidectomy) was applied in 27 boys, 26 were primary (81% complete), 3 secondary (100% complete). 33% received no chemotherapy after surgery, in 41% VBP protocol (vinblastine, bleomycin, cisplatin) was given and in 26%o VIP protocol (ethoposide, ifosphamide, cisplatin). Two patients received also ABK (adriamycine, bleomycin, carboplatin). Among 26 children with germ cell tumours, 25 (96%) are alive, 23 (88%) are in first remission after completion of treatment. One child died due to central nervous system metastases. 2 children had local recurrence treated with chemotherapy or surgery with good result. Median follow-up is 45 months. TGM regimen is highly efficient in the treatment of malignant testicular tumours. Problems occur in cases of disseminated disease.
Medical Science Monitor, Mar 3, 1997
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Papers by Mariusz Wysocki