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.

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.
CONCLUSIONS: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.

OBJECTIVE: 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.

OBJECTIVE: 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.
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

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.

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.
METHODS: 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.
CONCLUSIONS: 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.

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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.

UNASSIGNED: 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.
UNASSIGNED: 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®).
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients.
METHODS: Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis.
RESULTS: After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy.
CONCLUSIONS: The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.