Incidence of bacterial and fungal infections in Polish pediatric patients with acute lymphoblastic leukemia during the pandemic.

The most common complications related to the treatment of childhood acute lymphoblastic leukemia (ALL) are infections. The aim of the study was to analyze the incidence and mortality rates among pediatric patients with ALL who were treated in 17 Polish pediatric hematology centers in 2020-2021 during the pandemic. Additionally, we compared these results with those of our previous study, which we conducted in the years 2012-2017. The retrospective analysis included 460 patients aged 1-18 years with newly diagnosed ALL. In our study, 361/460 (78.5%) children were reported to have microbiologically documented bacterial infections during chemotherapy. Ten patients (2.8%) died due to sepsis. Fungal infections were reported in 99 children (21.5%), of whom five (5.1%) died due to the infection. We especially observed an increase in bacterial infections during the pandemic period compared to the previous study. The directions of our actions should be to consider antibiotic prophylaxis, shorten the duration of hospitalization, and educate parents and medical staff about complications (mainly infections) during anticancer therapy. It is necessary to continue clinical studies evaluating infection prophylaxis to improve outcomes in childhood ALL patients.

Pediatric Hematology and Oncology Center Integrated by Telemedicine: Experience, Challenges and First Results of a Cross Border Network.

This article reports on the development, implementation and management of a German-Polish telemedicine network in the field of pediatric oncology and hematology in the Euroregion Pomerania. The achievements and challenges of joint medical case reviews involving patients and their care givers, as well as cross-border education activities for physicians, students and nursing staff, are presented. In addition to a progress report, the results of an evaluation of the participants and teachers, likewise the measurement of knowledge growth, are given.

Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A.

Introduction: In 2020, the new nationwide protocol of prophylaxis in Polish plasma-derived FVIII (pdFVIII) previously treated patients (PTPs) with severe hemophilia A (sHA) was introduced, resulting in the necessity of switching from pdFVIII to recombinant FVIII (octocog-alpha; rFVIII). The study aimed to: (1) assess the safety of switching from pdFVIII to rFVIII, (2) assess the safety and efficacy of pharmacokinetically based (PK-based) personalized prophylaxis in severe hemophilia A. Patients and methods: 151 children and adolescents receiving prophylaxis with a standard dose (40 U/kg 3 x weekly) of pdFVIII were included in this study. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were analyzed for all patients before enrollment. Using myPKFiT application, pharmacokinetic (PK) analysis followed by the selection of the optimal model of prophylaxis was performed in all patients. Two possible models of prophylaxis (standard-dose rFVIII versus PK-based rFVIII) were discussed, with parents leaving the choice to their decision. Parents reported all episodes of bleeds. Screening for inhibitor was performed every 3 months. ABR and AJBR were prospectively analyzed again after a minimum follow-up time of 26 weeks. Results: 141/151 (93.4%) patients completed the study. 34 patients decided to continue standard prophylaxis with rFVIII (Group I), whereas 107 were switched to PK-based prophylaxis (Group II). The risk of inhibitor development could be assessed in 137/151 (90.7%) patients. Only 2/137 (1.47%) patients (both on PK-based prophylaxis) developed low-titer inhibitor with its spontaneous elimination. The retrospective analysis of bleeds during the last 12 months of standard pdFVIII prophylaxis revealed that patients who decided to continue standard prophylaxis had historically lower ABR and AJBR than those who started PK-based personalized prophylaxis. After a minimum of 26 weeks, ABR and AJBR improved significantly in both groups. There was no significant difference in ABR and AJBR between Group I and Group II during the follow-up period. However, the rate of reduction of ABR and AJBR was higher in patients on PK-based personalized prophylaxis. Conclusion: (1) Switching from pdFVIII to rFVIII (octocog-alpha) in PTPs with sHA is safe, (2) PK-based personalized prophylaxis may decrease ABR and AJBR in children and adolescents with sHA.

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.

Chromosomal Location of Pm12-A Novel Powdery Mildew Resistance Gene from Avena sterilis.

Identification of new, effective disease resistance genes is a very important aspect of plant breeding. Also important is the precise location of individual loci and tagging them with DNA markers for marker assisted selection. The aim of the present study was identification of the molecular markers linked with Pm12, a new effective resistance gene to powdery mildew, and their location in the oat genome. The analysis was performed on 167 F2 individuals from a hybrid of Fuchs × CN67383, with the status of the locus in each individual verified by progeny test in F3. Segregation ratios confirmed the monogenic nature of resistance. Making use of the sequence data of DNA markers and the oat OT3098 v2 genome reference assembly, Pm12 is located on chromosome 7C. A comparison was also made with the reference consensus map, to which there are more reports of mapped genes to date. The mapping results suggest that Pm12 is located in the interval 103.8-111.7 cM on this map. No powdery mildew resistance locus has been identified in this region so far, suggesting that Avena sterilis CN67383 carries a novel locus offering effective resistance in oat breeding. The information included in the oat genome annotation allowed for the identification of candidate genes in the close region of the marker cluster for Pm12. This information may provide an interesting source of further analysis of the pathways of various genes in response to the stress of powdery mildew infection.

Viral Infection Profile in Children Treated for Acute Lymphoblastic Leukemia-Results of Nationwide Study.

Viral infections can be a serious complication of therapy in children with acute lymphoblastic leukemia (ALL). In this study, we focused on the incidence and the profile of viral infection in children with ALL treated in 17 pediatric oncology centers in Poland in the two-year periods of 2018-2019 and 2020-2021. We also compared the frequency of viral infections in 2018-2019 to that in 2020-2021. In 2020-2021, a total of 192 children with ALL had a viral infection during intensive chemotherapy. A total number of 312 episodes of viral infections were diagnosed. The most common infections detected in the samples were: COVID-19 (23%), rhinovirus (18%), and respiratory syncytial virus (14%). COVID-19 and BK virus infections were the reason for the death 1% of all patients. In 2018-2019, a total of 53 ALL patients who had a viral infection were reported and 72 viral events were observed, mainly adenovirus (48.6%), rotavirus (31.9%), and herpes zoster (8.3%). No deaths were reported during this period. The cumulative incidence of viral infections in 2018-2019 was 10.4%, while for 2020-2021, it was 36.7%. In conclusion, a high incidence of COVID-19 infection was observed among pediatric patients with ALL in Poland. The mortality rate in our material was low. The viral profile in ALL children undergoing chemotherapy can be useful for clinicians to improve prophylactic and therapeutic strategies.

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.

Virulence Structure and Genetic Diversity of Blumeria graminis f. sp. avenae from Different Regions of Europe.

The structure and dynamics of changes in pathogen populations can be analysed by assessing the level of virulence and genetic diversity. The aim of the present study was to determine the diversity of Blumeria graminis f. sp. avenae populations. Diversity and virulence of B. graminis f. sp. avenae was assessed based on 80 single-spore isolates collected in different European countries such as Poland (40 isolates), Germany (10), Finland (10), Czech Republic (10) and Ireland (10) using ISSR (Inter-Simple Sequence Repeats) and SCoT (Start Codon Targeted) markers. This work demonstrated differences in virulence of B. graminis f. sp. avenae isolates sampled from different countries. Molecular analysis showed that both systems were useful for assessing genetic diversity, but ISSR markers were superior and generated more polymorphic products, as well as higher PIC and RP values. UPMGA and PCoA divided the isolates into groups corresponding with their geographical origin. In conclusion, the low level of genetic differentiation of the analysed isolates has suggested that the evolution of B. graminis f. sp. Avenae population is slow, and thus the evolutionary potential of the pathogen is low. This work paves the way for future studies on B. graminis f. sp. Avenae population structure and dynamics based on genetic variability.

Multicolor flow cytometry immunophenotyping and characterization of aneuploidy in pediatric B-cell precursor acute lymphoblastic leukemia.

The aim of this study was to assess the incidence of DNA aneuploidy in Polish children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and the relationship between aneuploidy and immunological phenotype, age, leukocyte count, S-phase fraction (SPF) and early response to induction chemotherapy assessed by the percentage of residual blast cells in bone marrow aspirates. The study group consisted of 267 patients. DNA content and immunophenotype were assessed in the bone marrow before treatment using multicolor flow cytometry (FC). DNA aneuploidy was detected in 50/267 (19%) patients. High hyperdiploidy was found to be associated with lower leukocyte count (p = 0.006) and common ALL immunophenotype. Flow cytometry analysis revealed that high hyperdiploid BCP-ALL patients showed significantly higher expression of CD9, CD20, CD22, CD58, CD66c, CD86 and CD123 antigens as compared to other groups of ploidy. In contrast, CD45 showed decreased expression. The percentage of leukemic blasts at diagnosis was lower in high hyperdiploid BCP-ALL cases than in diploid (79% vs. 85.7%, p = 0.001). The difference in minimal residual disease (MRD) levels on day 15 and 33 of induction therapy between analyzed groups was not significant. This study showed that high hyperdiploidy is associated with lower WBC count and specific immunological phenotype. Flow cytometric evaluation of expression of selected antigens can be used for fast identification of markers of aneuploidy in pediatric BCP-ALL, before genetic tests results are available. Understanding the biological significance of aneuploidy in leukemia can potentially be exploited therapeutically using targeted therapies against specific blast cell subclones.

COVID-19 in pediatric cancer patients is associated with treatment interruptions but not with short-term mortality: a Polish national study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently constitutes the leading and overwhelming health issue worldwide. In comparison with adults, children present milder symptoms, with most having an asymptomatic course. We hypothesized that COVID-19 infection has a negative impact on the continuation of chemotherapy and increases nonrelapse mortality. MATERIAL AND METHODS: This study was performed to assess the course of SARS-CoV-2 among children with hematological or oncological malignancies and its impact on cancer therapy. Records of SARS-CoV-2 infection in 155 children with malignancies from 14 Polish centers for pediatric hematology and oncology were collected and analyzed. RESULTS: SARS-CoV-2 replication was observed in 155 patients. Forty-nine patients were symptomatic, with the following being the most common manifestations: fever (31 patients), gastrointestinal symptoms (10), coryza (13), cough (13) and headache (8). In children who were retested, the median time of a positive PCR result was 16 days (range 1-70 days), but 12.7% of patients were positive beyond day + 20. The length of viral PCR positivity correlated with the absolute neutrophil count at diagnosis. Seventy-six patients did not undergo further SARS-CoV-2 testing and were considered convalescents after completion of isolation. Antibiotic therapy was administered in 15 children, remdesivir in 6, convalescent plasma in 4, oxygen therapy in 3 (1-mechanical ventilation), steroids in 2, intravenous immunoglobulins in 2, and heparin in 4. Eighty patients were treated with chemotherapy within 30 days after SARS-CoV-2 infection diagnosis or were diagnosed with SARS-CoV-2 infection during 30 days of chemotherapy administration. Respiratory symptoms associated with COVID-19 and associated with oxygen therapy were present in 4 patients in the study population, and four deaths were recorded (2 due to COVID-19 and 2 due to progressive malignancy). The probability of 100-day overall survival was 97.3% (95% CI 92.9-99%). Delay in the next chemotherapy cycle occurred in 91 of 156 cases, with a median of 14 days (range 2-105 days). CONCLUSIONS: For the majority of pediatric cancer patients, SARS-CoV-2 infection does not result in a severe, life-threatening course. Our data show that interruptions in therapy are common and can result in suboptimal therapy.

Acute Lymphoblastic Leukemia in Children: Better Transplant Outcomes After Total Body Irradiation-based Conditioning.

BACKGROUND/AIM: Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)- or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT). PATIENTS AND METHODS: Patients undergoing allo-HCT for Acute lymphoblastic leukemia (ALL) conditioned either with TBI (n=55) or chemotherapy (n=84) were compared. The following transplant outcomes were analyzed: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS). RESULTS: All analyzed long-term transplant outcomes were significantly better for patients conditioned with TBI at 2 years after transplant. OS at 2 years was 84% after TBI and 60.5% after chemotherapy-conditioning (p=0.005). Risk factor analysis showed that two factors, TBI-based conditioning and transplant in first remission of ALL, significantly improved OS, EFS, GRFS, and decreased RI. CONCLUSION: TBI-based conditioning before allogeneic HCT in children with acute lymphoblastic leukemia provides significantly better transplant outcomes, when compared to chemotherapy-based conditioning.

Virulence Structure of Blumeria graminis f. sp. avenae Populations in Poland across 2014-2015.

The purpose of this study was to determine the virulence structure of oat powdery mildew (Blumeria graminis f. sp. avenae, Bga) populations in Poland collected in 2014 and 2015. Powdery mildew isolates were collected from 18 locations in Poland. In total, nine lines and cultivars of oat, with different mildew resistance genes, were used to assess virulence of 180 isolates. The results showed that a significant proportion of the Bga isolates found in Poland were virulent to differentials with Pm1, Pm3, Pm6, and Pm3 + Pm8 genes. In contrast Pm4, Pm5, Pm2, and Pm7 genes were classified as resistant to all pathogen isolates used in the experiment. Based on obtained results we can state that there are differences in virulence pattern and diversity parameters between sites and years, but clear trends are not deducible.

Is Every Wild Species a Rich Source of Disease Resistance? Avena fatua L.-Potential Donor of Resistance to Powdery Mildew.

Identifying effective sources of disease resistance is an important aspect of an effective plant protection strategy. Wild species related to cultivars constitute a rich reservoir of resistance genes. Studies conducted in oat have shown that wild species are donors of resistance genes to crown and stem rust, powdery mildew or fusarium head blight. The aim of the present study was to prove whether A. fatua could be a source of effective resistance genes to powdery mildew. This species is widespread all over the world due to its very good adaptability and can be regarded as a potential source of resistance to fungal diseases, including powdery mildew. The conducted research has shown that A. fatua is a species with a low level of resistance to powdery mildew when compared to other wild species of the genus Avena L. A total of 251 accessions were evaluated, and only 23 were identified as resistant to the individual isolates used in the host-pathogen tests. It follows that resistance to powdery mildew is not common among wild Avena species, and its good environmental adaptation is not associated to resistance to powdery mildew.

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.

Clinical Outcome in Pediatric Patients with Philadelphia Chromosome Positive ALL Treated with Tyrosine Kinase Inhibitors Plus Chemotherapy-The Experience of a Polish Pediatric Leukemia and Lymphoma Study Group.

The treatment of children with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL Ph+) is currently unsuccessful. The use of tyrosine kinase inhibitors (TKIs) combined with chemotherapy has modernized ALL Ph+ therapy and appears to improve clinical outcome. We report herein the toxicity events and results of children with ALL Ph+ treated according to the EsPhALL2010 protocol (the European intergroup study of post-induction treatment of Philadelphia chromosome positive ALL) in 15 hemato-oncological centers in Poland between the years 2012 and 2019. The study group included 31 patients, aged 1-18 years, with newly diagnosed ALL Ph+. All patients received TKIs. Imatinib was used in 30 patients, and ponatinib was applied in one child due to T315I and M244V mutation. During therapy, imatinib was replaced with dasatinib in three children. The overall survival of children with ALL Ph+ treated according to the EsPhALL2010 protocol was 74.1% and event-free survival was 54.2% after five years. The cumulative death risk of the study group at five years was estimated at 25.9%, and its cumulative relapse risk was 30%. Our treatment outcomes are still disappointing compared to other reports. Improvements in supportive care and emphasis placed on the determination of minimal residual disease at successive time points, which will impact decisions on therapy, may be required.

Results of two consecutive treatment protocols in Polish children with acute lymphoblastic leukemia.

The aim of the study was to retrospectively compare the effectiveness of the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols and the distribution of risk groups by the two protocols after minimal residual disease (MRD) measurement as well as its impact on survival. We reviewed the medical records of 3248 patients aged 1-18 years with newly diagnosed ALL who were treated in 14 hemato-oncological centers between 2002 and 2018 in Poland. The overall survival (OS) of 1872 children with ALL treated with the ALL IC 2002 protocol was 84% after 3 years, whereas the OS of 1376 children with ALL treated with the ALL IC 2009 protocol was 87% (P < 0.001). The corresponding event-free survival rates were 82% and 84% (P = 0.006). Our study shows that the ALL IC-BFM 2009 protocol improved the results of children with ALL compared to the ALL IC-BFM 2002 protocol in Poland. This analysis confirms that MRD marrow assessment on day 15 of treatment by FCM-MRD is an important predictive factor.

Clinical characteristics and outcome of pediatric patients diagnosed with Langerhans cell histiocytosis in pediatric hematology and oncology centers in Poland.

BACKGROUND: Langerhans cell histiocytosis (LCH) affects 1-2 in 1,000,000 people. The disease is not associated with increased risk of treatment failure (especially among older children), but appropriate procedures implemented in advance can eliminate complications which might appear and significantly worsen the patients' quality of life. Thus, we sought to evaluate the clinical features, management, and outcome of children with LCH treated in Polish pediatric hematology-oncology centers. MATERIALS AND METHODS: One hundred eighty two patients with LCH were treated according to the Histiocytic Society Guidelines between 2010 and 2017. The participating centers were requested to provide the following data: demographic, clinical, as well as local or systemic treatment data and patients' outcome. Overall survival (OS) and event free survival (EFS) were estimated by Kaplan-Meier methods and compared using the log-rank test. RESULTS: Sixty nine percent of children were classified as single system (SS). The patients with SS disease were significantly older as compared to the children with multisystem disease (MS), 6 vs. 2.3 years respectively (p 0.003). Bones were involved in 76% of patients. Systemic treatment was applied to 47% of children with SS disease and 98% with MS disease. Fourteen patients relapsed while two children died. OS and EFS in entire group were 0.99 and 0.91 respectively (with median follow-up 4.3 years). CONCLUSION: The treatment of LCH in Polish centers was effective, however, new approaches, including mutation analyses and good inter-center cooperation, are needed to identify patients who might require modification or intensification of treatment.