Efficacy, safety, and cost-effectiveness of pegylated PEG-rhg-CSF in pediatric patients receiving high-intensity chemotherapy: results from a phase II study.

Background: High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Methods: Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3-4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Results: Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3-4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Conclusion: Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.

First onset of persistent neutropenia in patient undergoing long-term clozapine treatment after vaccination against COVID-19 and SARS-CoV-2 infection in short interval - a case report. / Pierwszorazowa uporczywa neutropenia u pacjenta przewlekle leczonego klozapina po szczepieniu przeciwko COVID-19, krótko poprzedzajacym infekcje wirusem SARS-CoV-2 ­ opis przypadku.

Clozapine is one of the most effective antipsychotic drugs, but its use is limited due to the possibility of severe side effects, such as neutropenia and agranulocytosis. The risk of these complications is the highest at the beginning of the treatment, but they can occur later, particularly when additional risk factors are present. In the described case, either COVID-19 vaccination or the infection itself led to severe neutropenia, which recurred during subsequent independent trials of other antipsychotic drugs. The paper presents the case of a 23-year-old woman diagnosed with early-onset, treatment-resistant schizophrenia who had been undergoing clozapine treatment with satisfying outcome for over 10 years. A week after the first dose of an mRNA vaccine against COVID-19, the patient developed a severe SARS-CoV-2 infection and experienced an extreme neutropenia, followed by a change of treatment. Although the patient fully recovered from the infection, the re-stabilization of her mental state remained unsatisfactory. The introduction of various newly implemented antipsychotic drugs led to partial improvement or another decline in the neutrophil count, despite discontinuing the use of clozapine. The authors discuss a few possible pathomechanisms. Based on our current knowledge, this is the first reported case of persistent neutropenia triggered by various antipsychotic drugs following exposure to SARS-CoV-2 antigens.

Characteristics of oncology patients with fever and invasive bacterial infections diagnosed.

AIM: To describe the characteristics of febrile oncology patients seen in the Paediatric Emergency Department and microbiological characteristics of the invasive bacterial infections (IBIs) diagnosed. METHODS: We conducted a prospective observational study of febrile oncology patients seen between 2016 and 2022. We divided haematologic cancers by the aggressiveness of the chemotherapy received at the time. RESULTS: We included 418 episodes (272 haematologic cancers, 146 solid tumours). The median duration of fever was 2 h (interquartile range: 1-3) and 97.6% of patients were well-appearing on arrival. We diagnosed 61 IBIs (14.6%), including six episodes of bacterial sepsis. One other episode was coded as sepsis without microbiological confirmation, yielding seven episodes overall (1.7%). Rates of IBI and sepsis were higher among patients with high-risk haematologic cancers than those with low-risk haematologic cancers or solid tumours (22.9%, 5.4% and 10.3%, p < 0.01; 3.4%, 0% and 0.7%, p = 0.06, respectively). Leading causes were S. epidermidis (42.6%) and E. coli (14.7%). Gram-positive bacteria caused 67.2% of non-septic IBIs and 50% of septic episodes. CONCLUSION: Most febrile oncology patients are well-appearing and present with a very short history of fever. Prevalence of IBI and sepsis and the main disease-causing bacteria differ by cancer type and the presence of sepsis.

Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention.

PURPOSE: Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients. EXPERIMENTAL DESIGN: We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n = 10, mean age: 10.7 ± 6.6 years) and after a 6-month oral hygiene intervention (n = 9,mean age: 11.6 ± 5.27 years), and from 12 healthy controls. RESULTS: We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins. CONCLUSIONS AND CLINICAL RELEVANCE: SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.

Mecapegfilgrastim for prophylaxis of febrile neutropenia in children and adolescents with rhabdomyosarcoma or Ewing sarcoma: a prospective, single-arm, pilot study.

BACKGROUND: The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES. METHODS: In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 µg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile. RESULTS: In total, 2 of the 30 (6.7%, 95% CI: 0.82-22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28-45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0-5 years and the 13-18 years groups, and 2 patients experienced FN in the 6-12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0-5 years, 6-12 years, and 13-18 years groups, respectively. CONCLUSION: Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted. TRIAL REGISTRATION: This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.

Forty years of human G-CSF: A short history in time.

Human G-CSF was identified in 1984 at Memorial Sloan-Kettering Cancer Centre, New York. Based on these findings, recombinant G-CSF was developed by Amgen, Thousand Oaks. In 1987, clinical trials began using recombinant G-CSF in cancer patients following chemotherapy to reduce the duration of neutropenia and in patients with congenital neutropenia (CN) to increase the number of neutrophils. It has changed the quality of life for many cancer patients and saved the lives of many patients with (CN).

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.

PURPOSE: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications. METHODS: We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7 days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3 days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately. RESULTS: Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death. CONCLUSIONS: Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.

Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy-Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single-Centre Experience.

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%-69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%-48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%-70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%-69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%-27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%-25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11).

Meta-analysis revisiting the influence of UGT1A1*28 and UGT1A1*6 on irinotecan safety in colorectal cancer patients.

Aim: To evaluate the association between irinotecan safety and the UGT1A1 gene polymorphism in colorectal cancer (CRC) patients.Materials & methods: The studies were systematically searched and identified from three databases (PubMed, Embase and The Cochrane Library) until 28 February 2023. The relationships were evaluated using pooled odds ratio (OR).Results: A total of 30 studies out of 600 were included, comprising 4471 patients. UGT1A1*28 was associated with a statistically significant increase in the OR for diarrhea (OR: 1.59, 95% CI = 1.24-2.06 in the additive model; OR = 3.24, 95% CI = 2.01-5.21 in the recessive model; and OR = 1.95, 95% CI = 1.42-2.69 in the dominant model) and neutropenia (OR = 1.70, 95% CI = 1.40-2.06 in the additive model; OR = 4.10, 95%CI = 2.69-6.23 in the recessive model; and OR = 1.93, 95% CI = 1.61-2.31 in the dominant model). Subgroup analysis indicated consistent associations in both Asian and non-Asian populations. UGT1A1*6 was associated with a statistically significant elevation in the OR for diarrhea (only in the recessive model, OR = 2.42; 95% CI = 1.14-5.11) and neutropenia (across all genetic models).Conclusion: The UGT1A1*28 and UGT1A1*6 alleles might be a crucial indicator for predicting irinotecan safety in CRC.

[Box: see text].

Approach to Pancytopenia: From Blood Tests to the Bedside.

Pancytopenia is an uncommon abnormality detected on a full blood count. Features of presentation tend to be non-specific, and are due to impaired functions of the cell lines involved. These can include fatigue, infection and bleeding. However, the aetiology of pancytopenia is extensive. This narrative review aims to provide a minimally invasive diagnostic algorithm for generalist clinicians to approach pancytopenia, including investigations into the underlying aetiology, and when a referral to the haematologist is warranted for further investigations such as bone marrow aspiration and trephine biopsy.

A retrospective analysis of haematological side effects of olaparib in excess-weight and normal BMI patients with ovarian cancer.

Background: Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved in Europe for the treatment of platinum-sensitive patients with newly diagnosed or recurrent platinum-sensitive ovarian cancer with a confirmed BRCA mutation or homologous recombination deficiency (HRD). Epidemiological studies have shown an incompatible association between ovarian cancer and obesity, but there have also been scientific reports indicating that obesity, especially severe obesity, increases the risk of ovarian cancer. Olaparib has a wide range of side effects, especially anaemia and neutropenia, which may lead to dose reduction or therapy discontinuation. Therefore, therapeutic drug monitoring (TDM) is recommended. The aim of the study was a retrospective analysis of threshold value of the trough concentration of olaparib (Ctrough) and haematological adverse reactions after olaparib treatment (300 mg/12 h) in excess-weight and normal body mass index (BMI) patients with ovarian cancer. Materials and methods: The pilot study was conducted on 38 ovarian cancer patients who were divided into two groups: I - normal BMI patients (BMI = 18.5-24.9 kg/m2; n = 14), II - excess-weight patients, i.e. overweight and obese patients (BMI ≥ 25 kg/m2; n = 24). The severity of neutropenia and anaemia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). The values of the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and red blood cell distribution width (RDW) parameters were also taken into account. HPLC-UV method (λ = 254 nm) was applied to measure olaparib plasma concentrations. Results: There were no statistically significant differences in olaparib Ctrough between the groups - 1602.86 vs. 1567.40 ng/mL (p = 0.9156). However, the overweight and obese patients had slightly higher dose/kg-adjusted olaparib Ctrough - 204.17 vs. 159.32 ng/mL/mg/kg. The incidence of grade 1 anaemia in the groups was as follows: I - 42.86%, II - 41.67%. Grade 2 and 3 anaemia was observed only in group II - 4.17% and 8.33%, respectively. The incidence of neutropenia in the groups of patients was as follows: grade 1: group I - 21.43%, group II - 20.83%; grade 2: group I - 7.14%, group II - 4.17%. Conclusions: The incidence of haematological adverse reactions to olaparib, such as neutropenia and grade 1 anaemia in the group of overweight and obese patients was the same as in the normal BMI group. The overweight and obese patients were characterised by higher severity of haematological adverse reactions to olaparib and slightly higher dose/kg-adjusted olaparib Ctrough. After one month of treatment with olaparib the overweight and obese patients had significantly lower red blood cells (RBC) and haemoglobin (Hgb) levels than the patients with normal BMI, which may indicate that anaemia develops faster in this group of patients.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

BACKGROUND: Mecapegfilgrastim, a long-acting granulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. OBJECTIVE: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. METHOD: Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. RESULTS: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. CONCLUSION: In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Early and late complications of hematopoietic stem cell transplantation.

As autologous stem cell transplantation (ASCT) is increasingly frequent in some patients with multiple sclerosis (MS), the knowledge of its adverse effects is paramount. Early complications (within 30 from transplantation) are usually due to conditioning regimen and consequent neutropenia. They include infections and noninfectious complications, such as oral and intestinal mucositis, increases in liver enzymes, hemorrhagic cystitis, and worsening of neurologic symptoms. Infections in the early phase, particularly during neutropenia, are mainly of bacterial origin, such as bloodstream infections, pneumonia, central-venous catheter-related infections, urinary infections, and neutropenic typhlitis, followed by viral reactivations. Prophylaxis with acyclovir against reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) is recommended, while a preemptive strategy is used for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) management. Fungal infections are infrequent and mainly caused by Candida, thus fluconazole prophylaxis is used in some centers. Late complications include secondary autoimmune diseases: hematologic, such as immune thrombocytopenic purpura, autoimmune hemolytic anemia, or acquired hemophilia, or nonhematologic, such as thyroiditis, rheumatoid arthritis, or Crohn's disease. Other late complications are endocrinopathies and gonadal dysfunction with possible consequences on fertility. Particularly in women over 32 years of age, the risk of infertility and premature ovarian insufficiency can be significant. Thus, reproductive counseling with fertility preservation techniques if required is mandatory before ASCT.

Mecapegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in locally advanced nasopharyngeal carcinoma: A prospective phase II clinical study.

BACKGROUND: Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen. METHODS: A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen. RESULTS: The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles. CONCLUSION: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.

Novelties for the management of cytomegalovirus after kidney transplantation / Nouveautés dans la prise en charge du cytomégalovirus après transplantation rénale.

Cytomegalovirus (CMV) infection is the main opportunistic infection observed after kidney transplantation. Despite the use of prevention strategies, CMV disease still occurs, especially in high-risk patients (donor seropositive/recipient seronegative). Patients may develop complicated CMV, i.e. recurrent, refractory or resistant CMV infection. CMV prevention relies on either universal prophylaxis or preemptive therapy. In high-risk patients, universal prophylaxis is usually preferred. Currently, valganciclovir is used in this setting. However, valganciclovir can be responsible for severe leucopenia and neutropenia. A novel anti-viral drug, letermovir, has been recently compared to valganciclovir. It was as efficient as valganciclovir to prevent CMV disease and induced less hematological side-effects. It is still not available in France in this indication. Recent studies suggest that immune monitoring by ELISPOT or Quantiferon can be useful to determine the duration of prophylaxis. Other studies suggest that prophylaxis may be skipped in CMV-seropositive kidney-transplant patients given mTOR inhibitors. Refractory CMV is defined by the lack of decrease of CMV DNAemia of at least 1 log10 at 2 weeks after effective treatment. In case of refractory CMV infection, drug resistant mutations should be looked for. Currently, maribavir is the gold standard therapy for refractory/resistant CMV. At 8 weeks therapy and 8 weeks later, it has been shown to be significantly more effective than other anti-viral drugs, i.e. high dose of ganciclovir, foscarnet or cidofovir. However, a high rate of relapse was observed after ceasing therapy. Hence, other therapeutic strategies should be evaluated in order to improve the sustained virological rate.

L'infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Malgré les stratégies préventives, il persiste des maladies à CMV, notamment chez les patients à haut risque (donneur séropositif/receveur séronégatif). Certains patients présentent des formes complexes avec des récurrences et des infections réfractaires et/ou résistantes aux antiviraux. La prévention de l'infection à CMV repose soit sur une prophylaxie universelle, soit sur une stratégie préemptive. Chez les patients à haut risque, la stratégie prophylactique est le plus souvent utilisée. Elle repose sur l'utilisation du valganciclovir, qui peut être responsable de leucopénies et de neutropénies sévères. Un nouvel antiviral, le létermovir, qui n'est pas encore disponible sur le marché en France dans cette indication, a montré une efficacité similaire au valganciclovir avec peu d'effets secondaires hématologiques. Des études récentes suggèrent l'intérêt de l'immuno-surveillance par ELISPOT ou Quantiféron pour guider la durée de la prophylaxie. D'autres études suggèrent également la possibilité de se passer d'un traitement prophylactique anti-CMV chez des transplantés rénaux CMV-séropositifs recevant des inhibiteurs de la mTOR. Le CMV réfractaire est défini par une absence de baisse de la charge virale d'au moins 1 log10 après deux semaines de traitement efficace. En cas d'absence de baisse de la charge virale, une recherche de mutations de résistance aux antiviraux doit être effectuée. Actuellement, le maribavir constitue le traitement de référence pour les formes réfractaires et résistantes. La clairance virale à la fin du traitement, ou huit semaines plus tard, est significativement supérieure à celle observée avec les autres antiviraux tels que le ganciclovir donné à forte dose, le foscarnet, ou le cidofovir. Cependant, le taux de rechute à l'arrêt du traitement par maribavir reste important. D'autres stratégies thérapeutiques doivent être évaluées pour améliorer ce taux de réponse virologique soutenue.

Invasive candidiasis in dogs: A case report and review of the literature.

Invasive candidiasis is characterized by the systemic dissemination of Candida spp. and colonization of multiple organs. We are reporting a case of invasive candidiasis in a 3.5-year-old female mixed-breed dog with a history of limb injury. After clinical evaluation and complementary examinations a sepsis diagnose was established. The patient remained hospitalized under antibiotic therapy, dying three days later. Necropsy revealed white, nodular (pyogranulomas), and multifocal areas on the liver, button ulcers in the stomach and intestines, and a random lung consolidation. Impression smears were made from the liver and lung surface lesions during necropsy showing yeast and pseudohyphae structures. Fragments of these organs were sent for fungal culture and subsequent molecular etiologic characterization, identifying it as Candida albicans. Histological examination of different organs showed pyogranulomatous inflammation surrounding the necrosis areas, which were full of yeast and pseudohyphae, as evidenced by periodic acid Schiff and immunohistochemistry. Neutropenia, as a consequence of sepsis, associated with the use of antibiotics may have allowed yeast invasion and proliferation in the mucosa of the gastrointestinal tract, reaching the liver and lungs through hematogenous route. Invasive candidiasis is a rare canine disease, and no other cases of neutropenia associated with antibiotic therapy, as a predisposing factors, have been reported.

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity.

PURPOSE: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever. METHODS: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge. RESULTS: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia. CONCLUSION: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

Clinical and Microbiological Characteristics of Febrile Neutropenia During Induction Chemotherapy in Adults With Acute Leukemia.

BACKGROUND: Few studies regarding infectious causes of febrile neutropenia (FN) in Mexico are available. AIMS: We aimed to describe clinical and microbiological characteristics of FN episodes during induction chemotherapy in adults with acute leukemia. METHODS AND RESULTS: This retrospective cohort from a Mexican tertiary care center included adults with newly diagnosed acute leukemia between January 2014, and December 2018. Clinical and microbiological characteristics were summarized using descriptive statistics. Univariate analyses for associations between clinical characteristics and FN and/or death were made; logistic regression analysis was performed to assess relationships with FN. Kaplan-Meier survival estimates were modeled for antimicrobial prophylaxis and FN. Ninety-five patients were included. Median age was 28 (IQR 20-43), 49 (52%) were males, and 74 (78%) developed FN (74/95). Among these, 98% had an identified source of infection (73/74) and 65% had >1. Common infections were urinary tract infection (24%), bacterial sinusitis (20%), and bacterial pneumonia (19%). Gram-negatives were the most frequently isolated microorganisms (69%), followed by Gram-positives (21%), and fungi (9%). Antimicrobial prophylaxis was inversely associated with FN (aOR = 0.07, CI 0.008-0.060, p = 0.02). Invasive fungal diseases were associated with 30-day mortality (aOR = 9.46, 95% CI 1.66-54.05). CONCLUSION: Infections caused 98% of the FN episodes. Gram-negative bacteria are the most common pathogens.

Atypical presentation of Felty syndrome: Successful management with rituximab therapy-A case report and review of literature.

The atypical presentation of Felty syndrome, even without arthritis symptoms, needs further evaluation. Timely diagnosis of neutropenia and splenomegaly in patients with rheumatoid arthritis without joint symptoms is crucial for a better prognosis. Despite the rarity of the condition, clinicians should have a high index of suspicion, and multidisciplinary collaboration between rheumatology, hematology, and other specialists is required for accurate diagnosis.

Development and evaluation of high-resolution melting assays for direct and simultaneous pathogen identification in bloodstream infections in pediatric oncology patients.

Blood culture, the gold-standard method for identifying pathogens in bloodstream infections, is time-consuming and demonstrates low sensitivity. These drawbacks are related to high mortality, especially among pediatric oncology patients presenting febrile neutropenia episodes. Here we describe two novel High-Resolution Melting assays designed for pathogen detection in bloodstream infections. The assays were initially evaluated using five sepsis-associated pathogens. Both assays demonstrated 100 % specificity, detected as low as 100 fg of bacterial DNA, and exhibited reproducibility. Clinical isolates from blood cultures were 100 % identified by both assays. Moreover, blind and direct identification of blood samples from pediatric cancer patients demonstrated sensitivities of 61.5 % and 69.2 % for "Primer Set 1" and "Primer Set 2", respectively. Our study highlights the potential of HRM-based assays as a rapid and efficient diagnostic approach for sepsis-related microorganisms. Further advancements could enhance their clinical utility for better management of febrile neutropenia episodes, especially in pediatric oncology patients.