Impact of prophylaxis with rituximab on EBV-related complications after allogeneic hematopoietic cell transplantation in children.

Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.

Infections with Klebsiella pneumoniae in Children Undergoing Anticancer Therapy or Hematopoietic Cell Transplantation: A Multicenter Nationwide Study.

Background:Klebsiella pneumoniae is a nosocomial pathogen that causes severe infections in immunocompromised patients. The aim of the study was to conduct a microbiological and clinical analysis of K. pneumoniae infections in children with malignancies or undergoing hematopoietic cell transplantation in Poland. Methods: We conducted a retrospective, multicenter study including children and adolescents under 19 years old treated between 2012 and 2021. We analyzed patients' characteristics, microbiological data, and the outcomes of antibiotic therapy. Results: A total of 9121 newly diagnosed children were treated for malignancy and 1697 pediatric patients underwent hematopoietic cell transplantation. K. pneumoniae infections were diagnosed in 527 patients. Their overall incidence was 4.86% in pediatric hematology and oncology patients and 4.95% in patients who underwent hematopoietic cell transplantation. The incidence of infection was higher in patients with acute leukemia than with solid tumors (7.8% vs. 4.1%; OR = 2.0; 95% CI = 1.6-2.4; p < 0.0001). The most frequent source of infection was in the urinary tract at 55.2%. More than 57% of K. pneumoniae strains were extended-spectrum ß-lactamase-positive and almost 34% were multidrug-resistant. Infections with K. pneumoniae contributed to death in 3.22% of patients. Conclusions: K. pneumoniae is one of the most critical pathogens in children suffering from malignancies or undergoing hematopoietic cell transplantation. The incidence of multidrug-resistant K. pneumoniae strains is increasing and contributing to poor clinical outcome.

Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Matched unrelated donor transplantation versus haploidentical transplantation with post-transplant cyclophosphamide in children with acute myeloid leukemia: a PDWP-EBMT study.

In children with acute myeloid leukemia (AML) who lack a human leukocyte antigen (HLA) identical sibling, the donor can be replaced with an HLA-matched unrelated donor (MUD) or a haploidentical donor (haplo). We compared outcomes of patients <18 years with AML in first and second complete remission (CR1 and CR2) undergoing a hematopoietic stem cell transplantation (HCT) either with a MUD with anti-thymocyte globulin (ATG) (N=420) or a haplo HCT with post-transplant cyclophosphamide (PT-CY) (N=96) after a myeloablative conditioning regimen (MAC) between 2011 and 2021, reported to the European Society for Blood and Marrow Transplantation. A matched pair analysis was performed to adjust for differences among groups. The final analysis was performed on 253 MUD and 95 haplo-HCT. In the matched cohort, median age at HCT was 11.2 and 10 years and median year of HCT was 2017 and 2018, in MUD and haplo-HCT recipients, respectively. The risk of grade III-IV acute graft-versus-host disease (aGVHD) was significantly higher in the haplo group (hazard ratio [HR]=2.33, 95% confidence interval [CI]: 1.18-4.58; P=0.01). No significant differences were found in 2 years overall survival (OS; 78.4% vs. 71.5%; HR=1.39, 95% CI: 0.84-2.31; P=0.19), leukemia-free survival (LFS; 72.7% vs. 69.5%; HR=1.22, 95% CI: 0.76-1.95; P=0.41), CI of relapse (RI; 19.3% vs. 19.5%; HR=1.14, 95% CI: 0.62-2.08; P=0.68) non-relapse-mortality (NRM; 8% vs. 11%; HR=1.39, 95% CI: 0.66-2.93; P=0.39) and graft-versus-host free relapse-free survival (GRFS; 60.7% vs. 54.5%, HR=1.38, 95% CI: 0.95-2.02; P=0.09) after MUD and haplo-HCT respectively. Our study suggests that haplo-HCT with PT-CY is a suitable option to transplant children with AML lacking a matched related donor.

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.

Infection With Saprochaete Clavata in Children After Hematopoietic Cell Transplantation.

Septic shock is a very rare manifestation of invasive fungal disease (IFD) in children after allogeneic hematopoietic cell transplantation (allo-HCT). The objective of this paper is analysis of two cases of pediatric patients with IFD caused by Saprochaete clavata after allo-HCT. Literature data on this infection in children and its outcome were also summarized. Infection with Saprochaete clavate presenting with symptoms of septic shock was being reported in 4 children, and 2 of them survived the infection. In conclusion, with quick diagnosis and quick treatment, the outcome of therapy of infection with Saprochaete clavata was successful.

Therapy results in pediatric Hodgkin lymphoma - does less mean better? Experience from a single children's oncology center.

Therapy results in pediatric Hodgkin lymphoma reflect remarkable progress in pediatric oncology. In the last decade, relevant development of new therapeutic options for children with refractory or relapsed disease has been made. In this study, we retrospectively analyzed therapy results and risk factors in children treated in a single oncology center according to five therapeutic protocols. Data from 114 children treated by a single institution between 1997 and 2022 were analyzed. Classic Hodgkin lymphoma therapy results were divided into four therapeutic periods: 1997-2009, 2009-2014, 2014-2019, and 2019-2022. For nodular lymphocyte-predominant Hodgkin lymphoma, data from one therapeutic protocol was analyzed. For the entire group, the 5-year probability of overall survival was 93.5%. There were no statistically significant differences between therapeutic periods. The occurrence of B symptoms at diagnosis and incidence of relapse were risk factors for death (p = 0.018 and p < 0.001). Relapse occurred in 5 cases. The 5-year probability of relapse-free survival for the entire group was 95.2%, without significant differences between groups. Patients treated between 1997 and 2009 had over a sixfold higher risk for events, defined as primary progression, relapse, death, or incidence of secondary malignancies (OR = 6.25, p = 0.086). The 5-year probability of event-free survival for all patients was 91.3%. Five patients died, and the most common cause of death was relapse. Modern therapeutic protocols in pediatric Hodgkin lymphoma are marked by excellent outcomes. Patients with disease relapses have a notably high risk of death, and the development of new therapeutic options for this group remains one of the main goals of current trials.

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.

Case report: Cellular therapy for hydroa vacciniforme-like lymphoproliferative disorder in pediatric common variable immunodeficiency with chronic active Epstein-Barr virus infection.

Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein-Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.

Letermovir Prophylaxis for Cytomegalovirus Infection in Children After Hematopoietic Cell Transplantation.

BACKGROUND/AIM: Cytomegalovirus (CMV) infection is one of the major causes of morbidity following hematopoietic cell transplantation (HCT). Allogeneic HCT (allo-HCT) recipients are at the highest risk of clinically significant CMV reactivation. While letermovir has been approved for prophylactic use in CMV seropositive adults, reports on pediatric data are very limited. The objective of the study was to examine the use of letermovir for prophylaxis from CMV infection in children undergoing allo-HCT in a single center. PATIENTS AND METHODS: This retrospective matched-pair analysis study included 39 CMV-seropositive pediatric patients undergoing allo-HCT receiving letermovir as a primary prophylaxis for CMV infection on a compassionate-use basis (LMV group, n=13) or not (control group, n=26). There were no differences in basic characteristics between the analyzed groups. Among patients of the study group, 12 received primary prophylaxis with letermovir from day +1 after HCT. One patient, previously treated with ganciclovir received secondary prophylaxis from day +18. RESULTS: Prophylactic dose of letermovir was adjusted to cyclosporine co-administration, varied in between 120-480 mg, and given orally, once daily. No CMV reactivation was observed during administration of letermovir. Cumulative incidence of CMV reactivation was significantly higher for the control group not receiving prophylaxis. Of the 13 patients of the study group, three died; however, deaths were not attributable to CMV infection. We did not observe any toxicities related to letermovir. CONCLUSION: Our data support letermovir prophylaxis efficacy and safety in pediatric patients after allo-HCT. Compared with the historical group, prophylactic use of letermovir decreased the number of CMV reactivations in children.

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.

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.

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.

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.

Impact of Palifermin on Transplant Outcomes in Children and Adolescents Undergoing Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. PATIENTS AND METHODS: A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. RESULTS: In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. CONCLUSION: Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.

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.

Successful Management of Unusual Multiple Gut Colonization With Extremely Drug-resistant Bacteria in an Infant Undergoing Hematopoietic Cell Transplantation.

Enterobacterales represent a serious threat to transplant patients due to their increase frequency of carbapenem resistance and wide spreading. We present a case of an infant with acute lymphoblastic leukemia undergoing hematopoietic stem cell transplantation. Before transplantation an unusual double colonization of the gastrointestinal tract with extremely resistant Escherichia coli and Klebsiella pneumoniae strains producing metallo-beta-lactamase was diagnosed. Respective epidemiologic management was implemented, based on the strict reverse isolation in patient-protective environment, and intensified antimicrobial surveillance. After granulocyte recovery, no extremely drug-resistant strains were found, and no case of isolation and/or transmission of carbapenem-resistant bacteria has been identified in the transplant center during the following 6 months.