Relapse/Refractory Paediatric B-ALL Case with CD19- Phenotype Switching Indicating the Importance of Appropriate Diagnostic Approach and Targeted Treatment Adjustment-Case Report.

The case reported presents a rare CD19- phenotype shift of an acute lymphoblastic leukaemia clone during relapse/refractory ALL in a paediatric patient. We explore possible reasons for the promotion of CD19-negative cell selection, including discrete mutations and anti-CD19 treatment, which is gaining importance as targeted therapies such as blinatumomab enter standard treatment protocols. A 9-year-old male patient was diagnosed with B lymphocyte acute lymphoblastic leukaemia. Initial standard genetic analysis did not show significant chromosomal aberrations, and the patient underwent chemotherapy in line with the intermediate-risk protocol. After initially achieving remission, the disease relapsed, and the patient required hematopoietic stem cell transplantation (HSCT). In-depth retrospective microarray analysis performed at this point revealed additional risk factors, particularly a loss of function TP53 V173L mutation. A second recurrence was diagnosed which prompted targeted treatment application (blinatumomab) and subsequent HSCT. The third leukemic relapse, diagnosed shortly after the second HSCT, limited treatment options to last-resort CAR T-cell therapy in Germany. Subsequent immunophenotyping revealed insufficient CD19 expression by ALL clones and disqualified the patient from treatment. The patient died in October 2019 from disease progression. The case highlights the importance of in-depth molecular diagnostics and monitoring of relapse/recurrent ALL cases to identify and manage risk factors during treatment.

Fertility Preservation in Children and Adolescents during Oncological Treatment-A Review of Healthcare System Factors and Attitudes of Patients and Their Caregivers.

Oncofertility is any therapeutic intervention to safeguard the fertility of cancer patients. Anti-cancer therapies (chemotherapy, radiation therapy, etc.) entail the risk of reproductive disorders through cytotoxic effects on gamete-building cells, especially those not yet fully developed. This literature review analyzes the available data on securing fertility in pediatric and adolescent populations to identify the methods used and describe aspects related to financing, ethics, and the perspective of patients and their parents. Topics related to oncofertility in this age group are relatively niche, with few peer-reviewed articles available and published studies mostly on adults. Compared to pubertal individuals, a limited number of fertility preservation methods are used for prepubertal patients. Funding for the procedures described varies from country to country, but only a few governments choose to reimburse them. Oncofertility of pediatric and adolescent patients raises many controversies related to the decision, parents' beliefs, having a partner, ethics, as well as the knowledge and experience of healthcare professionals. As the fertility of young cancer patients is at risk, healthcare professionals should make every effort to provide them with an opportunity to fulfill their future reproductive plans and to have a family and offspring. Systemic solutions should form the basis for the development of oncofertility in pediatric and adolescent populations.

Cytogenetic findings in Polish patients with suspected Fanconi anemia.

BACKGROUND: The high sensitivity of cells of Fanconi anemia (FA) patients to DNA cross-linking agents (clastogens), such as mitomycin C (MMC), was used as a screening tool in Polish children with clinical suspicion of FA. OBJECTIVES: The aim of the study was to compare chromosome fragility between 3 groups, namely non-FA, possible mosaic FA and FA patients. MATERIAL AND METHODS: The study included 100 children with hematological manifestations and/or congenital defects characteristic of FA, and 100 healthy controls. Blood samples obtained from participants were analyzed using an MMC-induced chromosomal breakage test. RESULTS: Patients with clinical suspicion of FA were divided into 3 subgroups based on the MMC test results, namely FA, possible mosaic FA and non-FA. Thirteen out of 100 patients had a true FA cellular phenotype. The mean value of MMC-induced chromosome breaks/cell for FA patients was higher than for non-FA patients (6.67 ±3.92 compared to 0.23 ±0.18). In addition, the percentage of cells with spontaneous aberrations was more than 9 times higher in FA patients than in non-FA patients. CONCLUSIONS: Our results confirmed that the MMC sensitivity test distinguishes between individuals affected by FA, those with possible somatic mosaicism, and patients with bone marrow failure for other reasons, who were classified as non-FA in the first diagnostic step. However, a definitive differential diagnosis requires follow-up mutation testing and chromosome breakage analysis of skin fibroblasts.

Infections With Stenotrophomonas maltophilia in Children Undergoing Anticancer Therapy or Hematopoietic Cell Transplantation: A Multicenter Nationwide Study.

BACKGROUND: Infections caused by Stenotrophomonas maltophilia (SM) have documented high mortality rate in immunocompromised patients. AIM: This nationwide multicenter study was performed to analyze the epidemiology of SM infections in children undergoing anticancer therapy (pediatric hematology and oncology [PHO]) or hematopoietic cell transplantation (HCT) over 2012-2019, including incidence and outcome of SM infections, as well as treatment regimens and multidrug resistance. METHODS: Cumulative incidence of SM infections was calculated using the competing risk analysis from the day of diagnosis (PHO setting) or from the day of transplantation (HCT setting). The Kaplan-Meier method was used to determine survival from infection. RESULTS: During the study period of 8 years, a total number of 1356 HCTs and 7337 children newly diagnosed for malignancy were analyzed. Diagnosis of acute leukemia was a predisposing factor for SM infection. The cumulative incidence of SM infections was comparable in HCT patients in comparison to PHO (0.81% vs. 0.76%). High rate of trimethoprim/sulfamethoxazole susceptibility among SM isolates was observed in both groups of patients (80.8%). Although this was the drug of choice, survival rates from SM infections were significantly lower in HCT than in PHO (45% vs. 85%, P = 0.001, log-rank test). We found the transplant procedure and lack of clinical resolution after 18 days of antibiotic therapy to be independent mortality risk factors. CONCLUSIONS: The risk of SM infections and the occurrence of resistant bacterial strains in allo-HCT patients were comparable to PHO patients. Irrespective of target antibiotic therapy, the outcome of SM infections was better in the PHO setting.

Analysis of incidence and risk factors of the multidrug resistant gastrointestinal tract infection in children and adolescents undergoing allogeneic and autologous hematopoietic cell transplantation: a nationwide study.

The aim of this multi-center study was to evaluate the incidence, clinical course, and risk factors for bacterial multidrug-resistant (MDR) gastrointestinal tract infections (GTI) among children undergoing allogeneic and autologous hematopoietic cell transplantation. A total number of 175 pediatric patients (aged 1-18 years), transplanted between January 2018 and December 2019, who were tested for bacterial colonization/infection were enrolled into this multi-center analysis. Episodes of MDR GTI occurred in 77/175 (44%) patients. In multivariate analysis for higher GTI incidence, the following factors were significant: matched-unrelated donor (MUD) transplantation, HLA mismatch, presence of graft-versus-host disease (GVHD), and gut GVHD. The most common GTI were Clostridium difficile (CDI), multidrug-resistant Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli extended-spectrum ß-lactamase), and Enterococcus HLAR (high-level aminoglycoside-resistant). No MDR GTI-attributed deaths were reported. MDR GTI is a frequent complication after HCT among children, causes prolonged hospitalization, but rarely contributes to death. We identified risk factors of MDR GTI development in children, with focus on GVHD and unrelated donor and HLA mismatch. We conclude that the presence of Clostridiales plays an important anti-inflammatory homeostatic role and decreases incidence of GVHD or alleviate its course.

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.

Impact of decontamination therapy on gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic cell transplantation in children: Decontamination therapy in allo-HCT.

INTRODUCTION: Gut colonization with antibiotic-resistant bacteria (ARB) is associated with a significantly decreased overall survival in adult patients undergoing allo-HCT because of an increased treatment-related mortality. OBJECTIVE: The objective of this multicenter study was the analysis of impact of gut colonization status and the use of antibiotics on development of gastro-intestinal (GI) graft-versus-host disease (GVHD) of allo-HCT in children. METHODS: All consecutive patients who underwent allo-HCT over a period of three years in all pediatric HCT centers in Poland were analyzed for the impact of gut colonization on GI GVHD, with respect to standard of care including prophylaxis of infections and supportive therapy. RESULTS: At the time of allo-HCT, 44.2% of pediatric patients were colonized by ARB. Decontamination therapy with antibiotics was applied in 78% of children. Gut decontamination prophylactic therapy with antibiotics decreased the risk of acute GI GVHD. The use of gentamicin contributed to decreased rate of GVHD, while the use of ciprofloxacin and colistin contributed to increased incidence of GVHD after allo-HCT in children. Sepsis with ARB and non-MFD transplant contributed significantly to worse survival, while neither colonization nor gut decontamination had an impact on overall survival. CONCLUSIONS: Gut decontamination therapy contributed to lower incidence of acute GI GVHD in children undergoing allo-HCT, and the use of specific antibiotics might be responsible for this effect.

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.

Use of microarrays and MLPA for integrating diagnostics and personalizing treatment - Case report of a patient with Ph-like acute B-cell lymphoblastic leukemia.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood cancer. A special subtype of high risk BCP-ALL is Philadelphia-like ALL (Ph-like ALL), in which the gene expression profile is similar to BCR-ABL1-positive leukemia; however, fusion of the mentioned genes does not occur. The unfavourable clinical course and incidence of 15% of cases means that the diagnosis and therapeutic strategy of Ph-like ALL must be carefully developed and implemented into clinical practice. The study presents the case of a patient with diagnosed Ph-like ALL. The use of molecular analytical techniques has made it possible to identify a patient who is likely to relapse and who may benefit from personalized therapy This study shows the advantages of using genomic analyses to identify therapeutic targets, which is especially important for patients with high-risk disease. This model of management could be extended to other cancer subtypes, allowing for tailored diagnosis.

Diagnostic difficulties of AH1N1 influenza infection in children with acute lymphoblastic leukemia: Two case reports.

INTRODUCTION: Children with acute lymphoblastic leukemia (ALL) are at a risk of developing influenza-related complications. Approximately 10% of influenza-infected children with ALL or other types of cancer need intensive care, and 5% of them eventually die. PATIENTS' CONCERNS: We report 2 children with ALL and the swine-origin influenza A virus infection. Diagnosing influenza in them was a challenge. Medical records of these children were reviewed for demographic, clinical, and laboratory data. Patients were hospitalized in the Department of Pediatric Hematology, Oncology, and Transplantology of the Medical University of Lublin, Poland. Case 1 involved a 2-year-old girl who, according to acute lymphoblastic leukemia intercontinental Berlin-Frankfürt-Münster protocol 2009, started chemotherapy in July 2015. She was categorized in the intermediate risk group and received the induction and consolidation phase of the therapy without severe complications. The reinduction therapy was administered in the outpatient department till the 15 day. On the 20 day of this phase, she was admitted to our department with fever, mucositis, tachypnea, abdominal pain, and diarrhea. In September 2009, a 14-year-old boy (case 2) who, according to acute lymphoblastic leukemia intercontinental Berlin-Frankfürt-Münster protocol 2002, was categorized in the high-risk (HR) group, received the induction (Protocol I) phase of therapy without severe complications. On the 7 day of the HR-1 course, he manifested fever and strong, tiring cough, followed by strong mucositis. Chemotherapy had to be interrupted in both children. DIAGNOSIS: Respiratory viral infections, causing pneumonia, occurred in both patients during anticancer treatment. Initially, the real-time polymerase chain reaction test for the swine-origin influenza A was negative in both patients, which delayed the diagnosis. Additionally, bacterial, and fungal complications were also observed. INTERVENTIONS: Both patients received oseltamivir twice a day, a broad-spectrum antibiotic, antifungal drug, and granulocyte colony growth factor. OUTCOMES: The disease progressed quickly, and our patients subsequently died. CONCLUSION: We speculated that early antiviral treatment can help in the better management of patients in the HR group. It is also important to minimize influenza morbidity and mortality by vaccinating family members, using empiric therapy, providing immediate antiviral therapy, and educating parents about hygiene measures.

Varicella-zoster virus infection in the pediatric population with acute lymphoblastic leukemia in Poland.

Varicella-zoster virus (VZV) infection in pediatric hemato-oncology patients can be a therapeutic problem when children are exposed to immunosuppression. The aim of this study is to evaluate the incidence of VZV infection, antiviral therapy and outcome in children with ALL treated in polish hemato-oncological centers between 2012 and 2019 years. This study included medical records of 1874 patients, aged 1 to 18 years, with newly diagnosed acute lymphoblastic leukemia. During chemotherapy, 406 children out of 1874 (21.6%) experienced viral infections. The incidence of VZV infection in the whole group children with ALL was 1.8%. Among them, 34 (8.4%) patients were diagnosed with VZV infection. Thirty-five episodes of viral infections were identified. The median time of VCV therapy was 12 days. Herpes zoster infection occurred in 24 (70.6%) children, and varicella in 10 (29.4%) ones. The average time from the start of chemotherapy to the appearance of herpes zoster was 7.26 ± 4.05 months. VZV infection occurred mainly during the maintenance therapy, the reinduction and induction phases. There was no correlation between steroid dosage or type and subsequent zoster. The total lymphocyte count of these patients on the first day of zoster was reduced. No serious complications were observed due to this infection. All patients survived. In conclusion, a low incidence of VZV infection was observed among pediatric patients with ALL in Poland. This analysis indicates that currently used therapeutic methods are effective in children with cancer and VZV infection. The main focus should be on the prevention of delayed chemotherapy.

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.

First-line treatment failure in childhood acute lymphoblastic leukemia: The polish pediatric leukemia and lymphoma study group experience.

The aim of this study was to evaluate the risk factors of relapse and treatment-related deaths in acute lymphoblastic leukemia (ALL) in children residing in Poland.A total of 1872 patients with newly diagnosed ALL, treated according to the ALL IC-BFM 2002 protocol in 14 Polish pediatric hematology centers from 2002 to 2012 were included in the study. Three-hundred eighty-four patients experienced treatment failure. The last follow-up was 31 December, 2016.Univariate analysis identified factors in each risk group that were significantly different between children whose treatment failed and those who remained in the first remission. Multivariate analysis demonstrated that only the age of 10 years or over at primary diagnosis in the high-risk group was an adverse prognostic factor. To facilitate the analysis, patients were divided into three groups: relapsed children who survived; relapsed children who died; children without relapse who died due to toxicity.Our analysis showed that age older than 10 years is a particular risk factor for the failure of first-line of treatment, both in terms of relapse and treatment-related mortality.

Low seroprevalence and low incidence of infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) in pediatric hematopoietic cell transplantation donors and recipients: Polish nationwide study.

Toxoplasmosis is a potentially fatal complication after hematopoietic cell transplantation (HCT). Pre-transplant seropositivity of graft recipient to Toxoplasma gondii (Nicolle et Manceaux, 1908) is an important factor for disease reactivation after HCT. As toxoplasmosis epidemiology varies all over the world, we performed a Polish nationwide retrospective cohort study to determine the seroprevalence of toxoplasmosis in donors and pediatric allogeneic and autologous HCT recipients and the incidence of clinically evident toxoplasmosis in this patient group. Polish adult donors had higher anti-T. gondii seroprevalence than Polish pediatric donors (28% vs 8%; OR = 4.4; p = 0.02) and allo-HCT recipients (28% vs 17%; OR = 1.9; p = 0.01). Clinically apparent disease occurred in 1% of allo-HCT recipients: it was diagnosed by PCR as cerebral and/or ocular toxoplasmosis and successfully treated with antiprotozoal therapy. Regarding current practice, no prospective screening for infection of T. gondii in pediatric HCT centres is being performed, but, vast majority of HCT pediatric patients are receiving anti-T. gondii active prophylaxis. Since pre-HCT T. gondii serology was not assessed in all HCT; recipients, we propose this test should be a standard practice. Standardisation of management with infection of T. gondii in children after HCT is needed.

Impact of early chimerism status on clinical outcome in children with acute lymphoblastic leukaemia after haematopoietic stem cell transplantation.

BACKGROUND: The significance of very early chimerism assessment before day + 28, which is considered the moment of engraftment, is still unclear. In this retrospective study, we evaluated the clinical impact of very early chimerism on the clinical outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukaemia (ALL). METHODS: The study group included 38 boys and 18 girls. Very early chimerism was evaluated on days + 7, + 14, + 21 and + 28 after the transplant. Short tandem repeat polymerase chain reaction (STR PCR) was used to analyse chimerism. RESULTS: Overall survival (OS) and event-free survival (EFS) were 84 and 80%, respectively. The OS in the group of 24 patients with complete donor chimerism on day + 14 was 83%, and it did not differ statistically compared to the 32 patients with mixed chimerism on day + 14 (OS was 84%). In our cohort of patients, the matched unrelated donor, male gender of donor, number of transplanted cells above 4.47 × 106 kg and no serotherapy with anti-thymocyte globulin (ATG) were statistically related to a higher level of donor chimerism. The immunophenotypes of disease, age of patient at time HSCT, recipient sex, stem cell source (peripheral blood/bone marrow) and conditioning regimen had no impact on early chimerism. Acute graft versus host disease grades II-IV was diagnosed in 23 patients who presented with donor chimerism levels above 60% on day 7. CONCLUSIONS: The data presented in this study provide valuable insight into the analysis of very early chimerism in children with ALL treated with HSCT.

Influence of Mixed Chimerism on Outcome in Children With Anaemia After Haematopoietic Stem Cell Transplantation.

BACKGROUND/AIM: In patients with non-malignant diseases, mixed chimerism is not a rare phenomenon. The clinical impacts of chimerism following allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with congenital anaemia (CA) and severe aplastic anaemia (SAA) were analysed. PATIENTS AND METHODS: We studied twenty-seven consecutive children with congenital and acquired anaemia who had undergone allogeneic haematopoietic stem cell transplantations. In the observed group of patients, the median of the follow-up was 6.12 years (2.00-14.8 years). RESULTS: Overall survival (OS) did not depend on the type of disease p=0.1. OS did not significantly differ in patients who received more than 5x106/kg stem cells (91%) and those who received less than 5x106/kg (85%) (p=0.61). Two patterns of stable mixed chimerism (SMC) were observed: SMC (95-97% cells of the donor), and SMC with a fluctuation between 50-90% of the cells of the donor. None of the surviving patients received immunosuppression treatments of chronic Graft-versus-Host Disease (cGvHD). CONCLUSION: Our results showed that mixed chimerism did not influence the survival of children with congenital and aplastic anaemia following allo-HSCT.

Infection profile in children and adolescents with bone marrow failures treated with allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The objective of the study was to analyze the profile of infections in children with BMF following alloHCT. METHODS: Data of 169 consecutive children with inherited and acquired BMF treated with alloHCT between 2012 and 2017 in Polish pediatric transplant departments were analyzed in registry-based retrospective study, with respect to the type of infection, and clinical outcome. RESULTS: At least 1 infection was diagnosed in 107/169 patients (60.4%). In total, 182 infections were diagnosed. The most common were VI (96; 52.7%), followed by BI (71; 39.0%), and FI (15; 8.2%), P < .001. The most common etiological factors of VI were as follows: CMV (38.5%), EBV (22.9%), and BK virus (24%); while of BI were as follows: Staphylococcus spp. (17; 23.9%), Enterococcus faecium (10; 14.1%), and Klebsiella pneumoniae (9; 12.7%). No difference was found between the occurrence of infections with respect to donor type, graft source, and conditioning type. GvHD had no impact on the incidence of VI, BI, and FI. Fifteen FI were diagnosed in 12 patients, of which 14 FI were diagnosed in children transplanted for FA. Of total 107 children, 9 died (8.4%), of which 4 (3.7%) due to infections: bacterial sepsis (2) and invasive FI (2). CONCLUSION: Infections in children with BMF following alloHCT remain an important cause of morbidity. Children with FA had high incidence of FI. In our analysis, aGvHD had no impact on the occurrence on infections, although the study was not strong enough to prove such a difference.

Severe drug-induced hypertriglyceridemia treated with plasmapheresis in children with acute lymphoblastic leukemia.

Asparaginase (ASP) and steroids are a main part of treatment for ALL, in both front-line and relapse setting. It is known, that ASP can cause several toxicities such as hypersensitivity, pancreatitis, as well as severe lipid and coagulation disturbances. Administered steroids can result in diabetes, obesity, hyponatremia and also mild hyperlipemia, which can intensify side effects of asparaginase. When triglyceride elevation is greater than 1000 mg/dl, the risk of pancreatitis is significantly increased. We report two patients who were hospitalized in Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin in Poland and developed severe hypertriglyceridemia after receiving asparaginase and steroid therapy for acute lymphoblastic leukemia. These patients were treated using plasmapheresis. This procedure was performed with a venous catheter in the femoral vein and 5% albumin or fresh frozen plasma as the replacement fluid. We analysed the laboratory and clinical data of these children. Plasmapheresis was well tolerated in both cases and a decrease of hypertriglyceridemia was quickly observed. However, the girl developed pancreatitis. In our opinion, plasmapheresis appears to be safe and effective in reducing hypertriglyceridemia. We could recommend that this procedure should be performed early, as soon as the triglyceride level is above 1000 mg/dl, in order to prevent severe complications. Patients should continue chemotherapy without ASP. It is important to regularly monitor of the lipid profile, pancreatic enzymes and coagulation during ASP and steroids therapy.

Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: Impact of national programme of antifungal prophylaxis.

The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, paediatric hematology-oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of six consecutive years in nationwide study. A total number of 5628 patients with newly diagnosed malignancies and 971 patients after HCT (741 allo-HCT and 230 auto-HCT) were screened for infectious complications in biennial reports. IFD incidence was lower among PHO patients: 8.8% vs 21.2% (P < .0001) and survival from IFD was better: 94.2% vs 84.1% (P < .0001). Auto-HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo-HCT patients. Introduction of national antifungal prophylaxis programme in HCT and acute leukaemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients > 10 years old. Factors contributing to death with infection were as follows: undergoing HCT, diagnosis of acute leukaemia (ALL or AML) and duration of treatment of infection > 21 days. In conclusion, the incidence of IFD in allo-HCT and in AML patients on chemotherapy has decreased after introduction of national programme of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison with historical international data.