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.

Can CD34+CD38- lymphoblasts, as likely leukemia stem cells, be a prognostic factor in B-cell precursor acute lymphoblastic leukemia in children?

Background: CD34+CD38- lymphoblasts as likely leukemia stem cells (LSCs) may be responsible for a worse response to treatment and may be a risk factor for recurrence in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Objective: The study objective was to assess the prognostic role of CD34+CD38- lymphoblasts in bone marrow on the day of BCP-ALL diagnosis. Methods: 115 patients with BCP-ALL, the median age of 4.5 years (range 1.5-17.9 years), gender: female 63 (54.8%) with BCP-ALL were enrolled; Group I (n = 90)-patients with CD34+CD38+ antigens and Group II (n = 20)-patients with CD34+CD38- antigens on the lymphoblast surface. Results: A worse response on Days 8, 15, and 33 of therapy and at the end of treatment in Group II (CD34+CD38-) was more often observed but these differences were not statistically significant. A significantly higher incidence of BCP-ALL recurrence was in Group II. Conclusions: 1.In BCP-ALL in children, the presence of CD34+CD38- lymphoblasts at the diagnosis does not affect the first remission.2.In BCP-ALL in children, the presence of CD34+CD38- lymphoblasts at the diagnosis may be considered an unfavorable prognostic factor for disease recurrence.3.It is necessary to further search for prognostic factors in BCP-ALL in children.

Relapses Children's Acute Lymphoblastic Leukemia, Single Center Experience.

The prognosis in children and adolescents with relapsed ALL, despite intensive therapy, including hematopoietic stem cell transplantation, is still challenging. This study aims to analyze the incidence of relapsed ALL and survival rates in correlation to the risk factors. Materials and methods: 125 pediatric patients with ALL diagnosed in our department between 2000-2018; age 1−18 years old (median 6.4); female 53.6% vs. male 46.4%. Results: 19 pts (15.2%) were diagnosed with a relapse. Three pts (15.8%) had been diagnosed with very early relapses (2/3 T-ALL), 12 pts (63.1%) as an early relapse, and 4 pts (21.1%) as a late relapse. Bone marrow was the most frequent relapses localization. The five-year survival has been achieved by six patients (31.6%). A significant difference was found in regard to the five-year overall survival and relapse type (p < 0.05). The group with very early relapses (3/3; 100%) has not reached the five-year survival. Conclusions: 1. The main prognostic factor in children's ALL relapses is still the time of the onset of the relapse. 2. The T lineage acute lymphoblastic leukemia is a worse prognostic factor. 3. The analysis of the above relapse risk factors alongside cytogenethic markers and flow cytometry or polymerase chain reaction minimal residual disease is very important for first-line chemotherapy improvement and a more personalized choice of therapy for ALL patients.

Clear Cell Renal Cell Carcinoma, Diagnostic and Therapeutic Difficulties, Case Report and Literature Review.

Nephroblastoma is the most common kidney tumour in children, constitutes about 85% of cases. Although renal cell carcinoma (RCC) is the second-most common kidney malignancy in children, it constitutes only about 2-6% of all cases. Currently, the basis of children's RCC treatment is Umbrella Protocol of SIOP-RTSG, but, due to the rare diagnosis of this neoplasm in children, in difficult cases, treatment is based on the experience in adult patients with RCC. Nephrectomy improves prognosis and is usually performed at the first step of treatment. Acute kidney injury secondary to urolithiasis in a patient after nephrectomy due to RCC is a unique, very serious complication. Study design: We present a case of a 10-year-old boy with metastatic clear cell renal cell carcinoma (ccRCC) of the right kidney and an acute renal failure of the left kidney secondary to uric acid nephrolithiasis. Partial regression of the spread of ccRCC after 12.5-month treatment with sunitinib, followed by progression being observed and satisfactory effects and tolerance of nivolumab were observed later. Comorbidity of acute kidney injury during nephrolithiasis and ccRCC after nephrectomy in children is unique. Drugs used in the treatment clear cell carcinoma in adults (sunitinib and nivolumab), are also used in children with ccRCC.

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.

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.

Polish Multi-Institutional Study of Children with Ependymoma-Clinical Practice Outcomes in the Light of Prospective Trials.

We performed a multi-institutional analysis of 74 children with ependymoma to evaluate to what extent the clinical outcome of prospective trials could be reproduced in routine practice. The evaluation of factors that correlated with outcome was performed with a log rank test and a Cox proportional-hazard model. Survival was estimated with the Kaplan-Meier method. The majority of patients had brain tumours (89%). All had surgery as primary treatment, with adjuvant radiotherapy (RTH) and chemotherapy (CTH) applied in 78% and 57%, respectively. Median follow-up was 80 months and 18 patients died. Five- and 10-year overall survival (OS) was 83% and 73%. Progression was observed in 32 patients, with local recurrence in 28 cases. The presence of metastases was a negative prognostic factor for OS. Five- and 10-year progression-free survival (PFS) was 55% and 40%, respectively. The best outcome in patients with non-disseminated brain tumours was observed when surgery was followed by RTH (+/-CTH afterwards; p = 0.0001). Children under 3 years old who received RTH in primary therapy had better PFS (p = 0.010). The best outcome of children with ependymoma is observed in patients who received radical surgery followed by RTH, and irradiation should not be omitted in younger patients. The role of CTH remains debatable.

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.

The Treatment of Opsoclonus-Myoclonus Syndrome Secondary to Neuroblastic Tumours-Single-Centre Experience and Literature Review.

Background and Objectives: The opsoclonus-myoclonus syndrome (OMS) is characterised by opsoclons, myoclons and impaired balance, often concomitant with sleep disorder and behavioural difficulties. The symptoms develop as a result of autoimmune response triggered by a neuroblastic tumour (NT). OMS can also develop secondarily to a viral infection or as an immune response triggered by an unknown agent. This leads to the activation of B- and T-cells, which produce and release autoantibodies or cytokines directly within the central nervous system (CNS), thus damaging the neurons within the cerebellum and the brain stem. The available OMS treatments aim at decreasing lymphocyte, cytokine and autoantibody production or accelerating the utilisation of the latter. Another treatment option for OMS involves using cytostatic agents, which damage T- and B-cells causing their depletion and impaired function, which reduces their ability to produce antibodies and cytokines. Materials and Methods: We present a single-centre experience in treating OMS secondary to NT in 7 children. Results: The combined treatment with cyclophosphamide plus dexamethasone resulted in a complete resolution of OMS symptoms in 4 children, and a significant improvement in the 3 children. Two of them periodically present hyperactivity, and one girl requires an additional support at school due to special educational needs (SEN). Conclusions: NT resection does not resolve OMS in children with OMS secondary to NT. The combined treatment with dexamethasone plus cyclophosphamide seems to be an effective treatment of OMS.

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.

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.

Infectious complications in children with malignant bone tumors: a multicenter nationwide study.

Objectives: The analysis of epidemiology, risk factors and outcome of infections in children with malignant bone tumors (MBT) undergoing chemotherapy. Methods: In this retrospective nationwide multicenter cross-sectional study, a total number of 126 children with MBT including 70 with Ewing sarcoma (ES) and 56 with osteosarcoma (OSA) were screened for infections over a period of 72 consecutive months. Results: The risk of infection was 7.15-fold higher in patients with ES as compared to the OSA group, especially concerning bacterial infections (4.1-fold increase risk). Bacterial infections occurred in 74.3% patients with ES and in 41.1% with OSA. The median time from diagnosis to first infection was 4.9 months. 33.0% of bacterial episodes were diagnosed as bloodstream (BSI), 31.1% as gastrointestinal tract, 30.1% as urinary tract infection. Infection-related mortality (IRM) from bacterial infection was 6% and 15% in ES and OSA patients, respectively. Cumulative incidence was 7.1% for invasive fungal disease and 6.3% for viral infections. The only significant risk factor for IRM was time to infection ≥5 months since the beginning of chemotherapy. All patients who have died from infection had BSI and were in neutropenia. Conclusions: Infections in the children with MBT in our study occurred with high frequency, especially in patients with ES. The most frequent were bacterial infections, while fungal and viral infections were episodic. Among the bacterial infections, bloodstream, urinary tract and gastrointestinal tract infections occurred with similar frequency. All deceased patients died due to BSI. Bacterial infection occurring ≥5 months since the beginning of chemotherapy was a risk factor for death.

Infectious profile in children with ALL during chemotherapy: A report of study group for infections.

INTRODUCTION: The treatment-related mortality in currently published studies of acute lymphoblastic leukemia (ALL) in children is 2-4%, mainly due to infections. The aim of the study was to analyse the incidence, epidemiology, profile of infection and the death rate in children with ALL. PATIENTS AND METHODS: The retrospective analysis included 1363 patients, aged 1-18 years, with newly diagnosed ALL, who were treated in 17 pediatric hematology centers between 2012 and 2017 in Poland. The patients received therapy according to the ALL IC-BFM 2002 and 2009 (International Berlin-Frankfurt-Munster Study Group) protocols. RESULTS: In our study, 726 out of 1363 (53.2%) children were reported to have a microbiologically documented bacterial infection during chemotherapy. 1511 episodes of these infection were diagnosed. A total number of 251/1363 (18.4%) children experienced a viral infection. 304 episodes were documented by PCR test (polymerase chain reaction). A fungal infection was reported in 278 (20.4%) children, including 10.1% of probable, 6.0% of proven, 83% of possible diagnosis. A higher frequency of fungal infection was noted in the recent years. In our material, the rate of death was 2.4%, mainly due to fungal infection. CONCLUSIONS: Our results present the epidemiology of infectious disease in the Polish ALL patient population. The most frequent were bacterial infections, followed by fungal and viral ones. Similar to the previously published data, the mortality rate in our material was 2.4%.

Infections in children with acute myeloid leukemia: increased mortality in relapsed/refractory patients.

The aim of this nationwide study was to describe the epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD) and viral infections (VI) in patients with de novo and relapsed/refractory (rel/ref) acute myeloid leukemia (AML). Within the studied group of 250 children with primary AML, at least one infectious complication (IC) was diagnosed in 76.0% (n = 190) children including 85.1% (n = 504) episodes of BI, 8.3% (n = 49) - IFD and 6.6% (n = 39) - VI. Among 61 patients with rel/ref AML, at least one IC was found in 67.2% (n = 41) of children including 78.8% (n = 78) of BI, 14.1% (n = 14) of IFD and 7.1% (n = 7) of VI. In all AML patients, within BI Gram-negative strains were predominant. Half of these strains were multi-drug resistant. Characteristics of IFD and VI were comparable for de novo and rel/ref AML. The infection-related mortality was significantly higher, while survival from infection was significantly lower in patients with rel/ref disease.

Infectious complications in children treated for hodgkin and non-hodgkin lymphomas in polish pediatric leukemia/lymphoma study group: incidence, epidemiology and etiology.

The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.

Rhabdomyolysis: rare complications with a difficult prognosis in the course of anticancer treatment.

Rhabdomyolysis refers to a number of clinical and biochemical symptoms, which result from the destruction of skeletal muscles. The following triad of symptoms is considered typical: myalgia, muscle weakness, and dark urine. The most common reasons for rhabdomyolysis in children are infections. It has also been reported that rhabdomyolysis may be caused by chemotherapy drugs. The most difficult complication of rhabdomyolysis is renal failure. The authors present a 17-year-old boy diagnosed with Ewing sarcoma and a 16-year-old boy suffering from acute leukemia, both with rhabdomyolysis developed in the course of infection caused by Clostridium difficile, and drug-induced neutropenia.

Cervical ectopic thymus in a 9-month-old girl: diagnostic difficulties.

Ectopic cervical location of the thymus is a very rarely diagnosed developmental disorder in children. This anomaly is usually manifested clinically as a neck tumor suggesting lymphadenopathy, which is also differentiated from more frequently occurring cervical cysts, angiomas, or malignant neoplasms. A decisive examination is the histopathologic assessment of the tumor, supported by necessary immunoassays. A diagnostic process is sometimes very difficult and the results are ambiguous; what is more, this process has a decisive impact on the child's future life. Therefore, a histopathologic evaluation performed by 2 independent pathologists should become the standard procedure. We present the case of a 9-month-old girl, in whom, after a difficult diagnostic process, ectopic cervical location of the thymus was diagnosed.