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.
Background
Hodgkin (HL) and non‐Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%‐30% of lymphoma ...patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second‐line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear.
Objective
The aim of this population‐based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL.
Patients and methods
We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second‐line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally.
Results
Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram‐positives were predominant. The rate of multidrug‐resistant bacteria was high, especially for Gram‐negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection‐related mortality was comparable for each group.
Conclusions
The incidence of IC was comparable during first‐ and second‐line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.
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.
Safe switching from a pdFIX (Immunine®) to a rFIX (Bax326) Solano Trujillo, M. H.; Stasyshyn, O.; Rusen, L. ...
Haemophilia : the official journal of the World Federation of Hemophilia,
September 2014, Letnik:
20, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Summary
The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of ...safety, efficacy and incremental recovery of a plasma‐derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12–65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti‐FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax3261) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.
Summary
A newly developed recombinant factor IX (BAX3261) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1–2%) ...haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment‐related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty‐six bleeds (19 non‐joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury‐related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1–2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B.
Eighteen children with steroid-sensitive nephrotic syndrome (SSNS) were studied. The control group comprised 20 healthy children. The following indirect parameters of reactive oxygen species activity ...were determined in nephrotic patients during four stages of the disease (full relapse before prednisone administration, disappearance of proteinuria, prednisone cessation, unmaintained remission): plasma malondialdehyde (MDA) levels, copper/zinc superoxide dismutase (CuZn SOD) activity and glutathione peroxidase (GPX) activity in erythrocytes, reduced glutathione (GSH) and vitamin C levels in whole blood, and vitamin E level in serum. Increased MDA levels, reduced vitamin C levels, and enhanced CuZn SOD activity were found in relapse. GSH concentration was high during all four stages. Vitamin E level was also increased, parallel to the pattern of serum lipids. GPX activity remained low during the proteinuria stage and in remission. We conclude that the majority of abnormal findings can be attributed to the hyperlipidemia of NS. Low GPX activity may be a factor limiting the antioxidant capacity in NS. The present study is inconclusive regarding the role of free radicals in the proteinuria of NS.
Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening condition characterized by hemoptysis, dyspnoea, alveolar infiltrates on chest radiograph and various degrees of anemia. It may occur ...either as a primary disease of the lungs or a secondary condition due to cardiac, systemic vascular, collagen or renal diseases. Idiopathic pulmonary hemosiderosis (IPH) is a separate form of DAH of unknown origin, associated in some cases with celiac disease. The estimated incidence of IPH in children is 0.24-1.23 cases per million, with a mortality rate as high as 50%. Only about 500 cases of this disease have been described in medical literature. We present a case of a 9-year-old girl diagnosed with IPH, which was confirmed by the presence of many hemosiderin-laden macrophages in bronchoalveolar lavage obtained by bronchofiberoscopy. Therapy with glucocorticoids was initiated with a partial and transient response. Azathioprine and a gluten-free diet were subsequently introduced. However, the girl still suffers from recurrent episodes of hemoptysis, dyspnea and anemia.
Several reports indicate that lungs are the extralymphatic site most commonly affected in patients with Hodgkin lymphoma; however, the data in children are rather limited. This retrospective study ...aimed to assess the frequency, clinical picture, and the impact on prognosis in children with pulmonary Hodgkin lymphoma, who were diagnosed and treated in a single center during a 10-year period. Pulmonary lesions related to HL: nodules and parenchymal infiltrates with cavitations were found in 3 of 32 (9.4%) patients; in 2 cases these were found as the concomitant manifestation whereas in 1 case as the solitary form (Primary Pulmonary Hodgkin Lymphoma). B-DOPA and MVPP chemotherapy combined with mediastinal and pulmonary irradiation resulted in sustained remissions in all 3 patients, lasting 3, 7, and 64 months, respectively. Lung involvement occurs in up to 10% of children with Hodgkin lymphoma. Primary pulmonary Hodgkin lymphoma is a rare and atypical form of Hodgkin lymphoma; thus is associated with delayed diagnosis which does not seem to affect prognosis. It should be suspected in a child with non-resolving pneumonia and pulmonary parenchymal infiltrates with cavitations.
Although inhibition of the renin-angiotensin system delays the progression of renal failure in adults with chronic kidney disease, the blood-pressure target for optimal renal protection is ...controversial. We assessed the long-term renoprotective effect of intensified blood-pressure control among children who were receiving a fixed high dose of an angiotensin-converting-enzyme (ACE) inhibitor.
After a 6-month run-in period, 385 children, 3 to 18 years of age, with chronic kidney disease (glomerular filtration rate of 15 to 80 ml per minute per 1.73 m(2) of body-surface area) received ramipril at a dose of 6 mg per square meter of body-surface area per day. Patients were randomly assigned to intensified blood-pressure control (with a target 24-hour mean arterial pressure below the 50th percentile) or conventional blood-pressure control (mean arterial pressure in the 50th to 95th percentile), achieved by the addition of antihypertensive therapy that does not target the renin-angiotensin system; patients were followed for 5 years. The primary end point was the time to a decline of 50% in the glomerular filtration rate or progression to end-stage renal disease. Secondary end points included changes in blood pressure, glomerular filtration rate, and urinary protein excretion.
A total of 29.9% of the patients in the group that received intensified blood-pressure control reached the primary end point, as assessed by means of a Kaplan-Meier analysis, as compared with 41.7% in the group that received conventional blood-pressure control (hazard ratio, 0.65; confidence interval, 0.44 to 0.94; P=0.02). The two groups did not differ significantly with respect to the type or incidence of adverse events or the cumulative rates of withdrawal from the study (28.0% vs. 26.5%). Proteinuria gradually rebounded during ongoing ACE inhibition after an initial 50% decrease, despite persistently good blood-pressure control. Achievement of blood-pressure targets and a decrease in proteinuria were significant independent predictors of delayed progression of renal disease.
Intensified blood-pressure control, with target 24-hour blood-pressure levels in the low range of normal, confers a substantial benefit with respect to renal function among children with chronic kidney disease. Reappearance of proteinuria after initial successful pharmacologic blood-pressure control is common among children who are receiving long-term ACE inhibition. (ClinicalTrials.gov number, NCT00221845.)
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