No abstract

This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

We prospectively examined whether surface expression of Cytokine Receptor-Like Factor 2 (CRLF2) on leukemic blasts is associated with survival and induction treatment response in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Flow cytometric analysis of bone marrow-derived leukemia cells revealed that 7.51% (29/286) of 386 pediatric BCP-ALL patients were CRLF2-positive (CRLF2pos) at diagnosis. The median minimal residual disease (MRD) was lower in CRLF2pos than CRLF2-negative (CRLF2neg) patients on day 15 (MRD15) after induction therapy [0.01% (0.001-0.42%) vs. 0.45% (0.05-3.50%); p=0.001]. By contrast, the MRD15 was higher in Ikaros family Zinc Finger Protein 1 (IKZF1)-deleted BCP-ALL patients than in BCP-ALL patients without IKZF1 deletions [1.18% (0.06-12.0%) vs 0.33% (0.03-2.6%); p=0.003]. Subgroup analysis showed that MRD15 levels were lower in IKZF1Δ/CRLF2pos patients than in IKZF1Δ/CRLF2neg patients [0.1% (0.02-5.06%) vs. 2.9% (0.25-12%); p=0.005]. Furthermore, MRD15 levels were higher in IKZF1WT/CRLF2neg patients than in IKZF1WT/CRLF2pos patients [0.40% (0.04-2.7%) vs. 0.001% (0.001-0.01%)]. Despite the low MRD15 levels, IKZF1Δ/CRLF2pos patients showed poorer relapse-free survival (RFS) than other patient groups (p=0.003). These findings demonstrate that surface CRLF2 expression is associated with increased risk of relapse in pediatric BCP-ALL patients harboring IKZF1 deletions.

Summary 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.