Characteristics and treatment results of refractory and relapsed acute myeloid leukaemia in paediatric patients treated in Polish Paediatric Leukaemia/Lymphoma Study Group institutions according to the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 and a review of novel treatment possibilities in paediatric acute myeloid leukaemia.

Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy. Material and methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children. Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001). Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes.

Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation.

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.

Mixed phenotype acute leukemia: Biological profile, clinical characteristic and treatment outcomes: Report of the population-based study.

OBJECTIVES: The aim of this population-based, retrospective study was to analyze biological and clinical features and treatment results in children diagnosed with MPAL in all Polish pediatric oncology centers between 2007 and 2018. METHODS: Among 2893 children and adolescents diagnosed and treated for acute leukemia, 39 (1.35%) patients fulfilled the WHO criteria of MPAL. The T/myeloid phenotype was most prevalent. RESULTS: Cytogenetics findings were seen in 2 (5.1%), while chromosomal abnormalities were found in 14 (35.9%) patients. Thirty-two patients achieved CR-1, including 23 (92.0%) treated with ALL-directed chemotherapy and 9 (64.3%) treated with AML-type induction regimens. Within these patients, 4 (12.5%) died due to treatment-related complications and 11 (34.4%) relapsed. Nineteen (63.3%) patients underwent allo-HSCT in CR-1 and 14 (73.7%) of them have been in CR-1. In total, 17 (43.6%) patients remain in CR-1 for 1-12 years, including 14 (58.3%) with T/myeloid MPAL. The 5-year pOS and pEFS were 51.8% and 44.2%, respectively. The overall survival for ALL-directed therapy was significantly better than the one for AML-type chemotherapy (P = .001). It was also better for patients who underwent HSCT in CR-1 (P = .001). CONCLUSIONS: The prognosis of MPAL is unsatisfactory, but initial treatment with ALL-directed chemotherapy consolidated with allo-HSCT improves the outcomes in MPAL.

Infectious complications after hematopoietic stem cell transplantation for primary immunodeficiency in children: A multicenter nationwide study.

PURPOSE: The aim of this nationwide study was to evaluate the characteristics of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in pediatric patients with PID after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: In total, 114 HSCT recipients were enrolled into the study. At least one infectious complication (IC) was diagnosed in 60 (52.6%) patients aged 0.1-17.7 years, that is, 59.5% with SCID and 49.4% with non-SCID. RESULTS: Among 60 HSCT recipients diagnosed with at least one IC, 188 episodes of infectious complications (EIC) were recorded, that is, 46.8% of BI, 41.5% of VI, and 11.7% of proven/probable IFD. According to PID and HSCT donor type, the incidence of EIC was comparable (P = .679). The localization of infections differed significantly due to PID type (P = .002). After each HSCT donor type, the most common site of infection was GI. Overall, BI caused by Gram-positive strains (59.1%) were prevalent, especially Staphylococcaceae. The multidrug-resistant (MDR) pathogens were diagnosed in 52.3%, especially ESBL + Enterobacteriaceae. The profile of VI was comparable for SCID and non-SCID patients (P = .839). The incidence of IFD was comparable for each PID and HSCT donor type. Survival after infection was 91.5% and was comparable for PID and HSCT donor type. CONCLUSIONS: The rate of patients diagnosed with IC among pediatric PID-HSCT recipients did not depend on PID type, but rather on HSCT donor type. The localization of IC depended on PID and HSCT donor type. Within bacterial infections, predominated Gram-positive strains and the MDR pathogens were responsible for more than half of EIC.

The influence of different intensity of treatment on hormonal markers of gonadal function in acute lymphoblastic leukemia survivors.

Anti-cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti-Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed-up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.

Development and current use of in hematopoietic stem cell transplantation in children and adolescents in Poland: Report of the Polish pediatric study group for hematopoietic stem cell transplantation of the Polish society for pediatric oncology and hematology.

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%). Among 788 auto-HSCTs, 30.8% were done for hematological malignancy (NHL 41.2%, AML 23.9%, HD 17.7%, ALL 15.6%, other 1.5%), while the remaining 69.2% for solid tumors (neuroblastoma 59.8%, Ewing's sarcoma 20.4%, other 19.8%). In Poland, between 1989-2016, the infrastructure indispensable to perform HSCT in every child with indication for this therapeutic procedure was created, and HSCT became an important part of pediatric treatment, especially in pediatric oncology, hematology, and in primary immunodeficiencies.

A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II-IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4-5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor.

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party.

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.

Elevated plasma ADMA contributes to development of endothelial dysfunction in children with acute lymphoblastic leukemia.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) survivors are at higher cardiovascular risk than the general population, which may result from anthracycline-related endothelial dysfunction (ED). However, a few studies indirectly show that ED may appear in ALL children before treatment begins. Hence, in this study we intended to verify the hypothesis that ED is part of the ALL phenotype. PATIENTS/METHODS: Twenty-eight ALL children and 14 healthy age-matched control children were recruited. The study group was examined at baseline, then at the 33rd and 78th day of treatment. At each step of the protocol endothelial vasodilative function was assessed by a laser Doppler flowmeter, which was followed by blood collecting for subsequent analyses. RESULTS: Compared to controls, the study group at baseline was characterized by significantly lower endothelial vasodilative responsiveness, accompanied by elevated asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations, which were correlated with lactate dehydrogenase (LDH) and aspartate transaminase (AST). Initial ALL treatment restored endothelial function, which followed changes in ADMA and LDH concentrations. DISCUSSION: This is the first demonstration that functionally assessed ED is present in ALL children at the diagnosis and results from elevated ADMA and parallel inflammatory ED.

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

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 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.

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.

The BCL-2 protein in precursor B acute lymphoblastic leukemia in children.

The BCL-2 protein plays an important role in controlling apoptosis. Disorders of this process can lead to the emergence and development of acute lymphoblastic leukemia (ALL) and can determine the resistance of leukemic cells to chemotherapy. The levels of BCL-2 mRNA were determined in 20 children with pre-B ALL using RT-polymerase chain reaction and the percentage of BCL-2+ cells in 51 patients using flow cytofluorometry. Similar levels of BCL-2 mRNA (P=0.18) with a higher percentage of cells BCL-2+ (P=0.04) were shown in the bone marrow of patients with pre-B ALL compared to normal peripheral blood mononuclear cells. We could not find any connection between the level of BCL-2 mRNA or the percentage of BCL-2+ cells and selected clinical features. A high percentage of BCL-2+ cells and high levels of BCL-2 mRNA did not affect the 5-year overall survival probability nor the 5-year relapse-free survival probability. These results may indicate a high activity of mechanisms promoting the development of the final form of the BCL-2 protein from mRNA in leukemic cells. A high BCL-2 level does not affect the clinical course or worsen the prognosis in children with ALL.

Clinical Characteristics and Treatment Outcomes of Myeloid Sarcoma in Children: The Experience of the Polish Pediatric Leukemia and Lymphoma Study Group.

Introduction: Myeloid sarcoma (MS) is an extramedullary malignant tumor composed of immature myeloid cells. It occurs in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). MS may coincide with disease diagnosis or precede bone marrow involvement by months or even years; it can also represent the extramedullary manifestation of a relapse (1, 2). Aim: The aim of this study is to describe clinical characteristics of children diagnosed with MS in Poland as well as to analyze diagnostic methods, treatment, and outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS). The study also attempted to identify factors determining treatment outcomes. Patients: The study group comprised 43 patients (F=18, M=25) aged 0-18 years (median age, 10.0 years; mean age, 8.8 years) diagnosed with MS based on tumor biopsy and immunohistochemistry or identification of underlying bone marrow disease and extramedullary tumor according to imaging findings. Methods: The clinical data and diagnostic and therapeutic methods used in the study group were analyzed. A statistical analysis of the treatment outcomes was conducted with STATISTICA v. 13 (StatSoft, Inc., Tulsa, OK, USA) and analysis of survival curves was conducted with MedCalc 11.5.1 (MedCalc Software, Ostend, Belgium). Statistical significance was considered at p<0.05. Results: In the study group, MS was most frequently accompanied by AML. The most common site of involvement was skin, followed by orbital region. Skin manifestation of MS was more common in the age group <10 years. The most frequent genetic abnormality was the t(8;21)(q22;q22) translocation. The 5-year OS probability (pOS), 5-year RFS probability (pRFS), and 5-year EFS probability (pEFS) were 0.67 ± 0.08, 0.79 ± 0.07, and 0.65 ± 0.08, respectively. In patients with isolated MS and those with concurrent bone marrow involvement by AML/MDS, pOS values were 0.56 ± 0.12 and 0.84 ± 0.09 (p=0.0251), respectively, and pEFS values were 0.56 ± 0.12 and 0.82 ± 0.08 (p=0.0247), respectively. In patients with and without the t(8;21)(q22;q22) translocation, pEFS values were 0.90 ± 0.09 and 0.51 ± 0.14 (p=0.0490), respectively. Conclusions: MS is a disease with a highly variable clinical course. Worse treatment outcomes were observed in patients with isolated MS compared to those with concurrent bone marrow involvement by AML/MDS. Patients with the t(8;21)(q22;q22) translocation were found to have significantly higher pEFS. MS location, age group, chemotherapy regimen, surgery, and/or radiotherapy did not have a significant influence on treatment outcomes. Further exploration of prognostic factors in children with MS is indicated.

[Assessment of lipid layer thickness of tear film in the diagnosis of dry-eye syndrome in children after the hematopoietic stem cell transplantation]. / Ocena grubosci warstwy lipidowej filmu lzowego w diagnostyce zespolu suchego oka u dzieci po przeszczepieniu allogenicznych komórek macierzystych ukladu krwiotwórczego.

UNLABELLED: 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 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. PURPOSE: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prevalence, Epidemiology, Etiology, and Sensitivity of Invasive Bacterial Infections in Pediatric Patients Undergoing Oncological Treatment: A Multicenter Nationwide Study.

Background: Infectious complications (IC) caused by bacterial strains often impede anticancer therapy. The study aimed to retrospectively analyze bacterial IC that could help predict the risk and optimize the empirical treatment for bacterial infections in pediatric cancer patients. Patients and Methods: Over a 72-month period, all-in 5,599 children with cancer: 2,441 patients with hematological malignancy (HM including acute leukemias, Hodgkin and non-Hodgkin lymphomas [NHLs], and Langerhans cell histiocytosis) and 3,158 with solid tumors (STs including central nervous system tumors, neuroblastoma, Wilms' tumor, soft tissue sarcoma, germ cell tumors, Ewing sarcoma, osteosarcoma, hepatoblastoma, and others) were enrolled into the study. Episodes of bacterial infectious complications (EBICs) confirmed by microbiological findings were reported by each hospital and analyzed centrally. Results: At least 1 EBIC was diagnosed in 2,155 (36.8%) children (1,281 [59.4%] with HM and 874 [40.6%] with ST; p < 0.001). All-in 4,860 EBICs were diagnosed including 62.2% episodes in children with HM and 37.8% in children with ST (p < 0.001). Having analyzed the source of infections, blood stream infections predominated, apart from NHL patients in whom the most common type was gut infections. The profile of bacteria strains was different in HM and ST groups (p < 0.001). However, in both groups the most common Gram-negative pathogen was Enterobacteriaceae, with the rate being higher in the HM group. Among Gram-negative strains low susceptibility to ceftazidime, whereas among Enterococcus spp. low susceptibility to vancomycin was noticed. The rate of multidrug-resistant (MDR) pathogens was high, especially for Gram negatives (47.7% vs. 23.9%; p < 0.001). The survival after infections was comparable for HM and ST patients (p = 0.215). Conclusions: The risk of bacterial IC in HM patients was higher than in the ST group. The high rate of MDR strains was detected in pediatric cancer patients, especially in those with HM.

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.

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.

[Prophylaxis of vitamin D deficiency--Polish recommendation 2009]. / Stanowisko Zespolu Ekspertów. Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D - 2009.

Adequate vitamin D intake and its status are important not only for bone health and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. Basing on current literature review and opinions of National Consultants and experts in the field, polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women have been established.

[Prophylaxis of vitamin D deficiency--Polish recommendations 2009]. / Polskie zalecenia dotyczace profilaktyki niedoborów witaminy D--2009.

Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.

[Long-term observations of children with acute lymphoblastic leukemia and high leukocytosis treated according to modified "New York" protocols (1987-2003)]. / Wieloletnie obserwacje dziec z ostra bialaczka limfoblastyczna i wysoka liczba krwinek bialych leczonych wedlug zmodyfikowanych protokolow "Nowy Jork" (1987-2003).

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 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.

[Genotyping and minimal residual disease study in children with acute myeloid leukemia: preliminary results]. / Genotypowanie i oznaczania choroby resztkowej u dzieci z ostra bialaczka mieloblastycznq: wstepne wyniki.

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, 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.