Sepsis Unveils T-cell Large Granular Lymphocytic Leukemia in the Setting of End-Stage Renal Disease: A Rare Hematologic Malignancy.

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder originating from natural killer cells or T lymphocytes. In this report, we present the case of a 66-year-old female initially treated for sepsis, with methicillin-sensitive Staphylococcus aureus identified on initial blood culture prompting intravenous (IV) antibiotic therapy. The patient met systemic inflammatory response syndrome criteria upon admission due to severe neutropenia. Persistent fever led to neurological symptoms, and imaging revealed lung abnormalities along with chronic changes on the CT scan of the head. Multidisciplinary consultations were sought, resulting in treatment adjustments including antifungals and filgrastim. Flow cytometry and bone marrow biopsy confirmed the diagnosis of LGL leukemia.

Vincristine-induced adverse events related to body weight in dogs treated for lymphoma.

BACKGROUND: Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs). HYPOTHESIS/OBJECTIVES: Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs. ANIMALS: One hundred and thirty-eight dogs with newly diagnosed lymphoma were treated with vincristine. METHODS: A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post-administration. Data were evaluated using logistic regression or ordinal logistic regression. RESULTS: Thirty-eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37). CONCLUSIONS AND CLINICAL IMPORTANCE: Vincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.

Effectiveness of G-CSF in chemotherapy for digestive system tumors: a systematic review of the Clinical Practice Guidelines for the Use of G-CSF 2022 delineated by the Japan Society of Clinical Oncology.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) reportedly reduces the risk of neutropenia and subsequent infections caused by cancer chemotherapy. Although several guidelines recommend using G-CSF in primary prophylaxis according to the incidence rate of chemotherapy-induced febrile neutropenia (FN), the effectiveness of G-CSF in digestive system tumor chemotherapy remains unclear. To address these clinical questions, we conducted a systematic review as part of revising the Clinical Practice Guidelines for the Use of G-CSF 2022 published by the Japan Society of Clinical Oncology. METHODS: This systematic review addressed two main clinical questions (CQ): CQ1: "Is primary prophylaxis with G-CSF effective in chemotherapy?", and CQ2: "Is increasing the intensity of chemotherapy with G-CSF effective?" We reviewed different types of digestive system tumors, including esophageal, gastric, pancreatic, biliary tract, colorectal, and neuroendocrine carcinomas. PubMed, Cochrane Library, and Ichushi-Web databases were searched for information sources. Independent systematic reviewers conducted two rounds of screening and selected relevant records for each CQ. Finally, the working group members synthesized the strength of evidence and recommendations. RESULTS: After two rounds of screening, 5/0/3/0/2/0 records were extracted for CQ1 of esophageal/gastric/pancreatic/biliary tract/colorectal/ and neuroendocrine carcinoma, respectively. Additionally, a total of 2/6/1 records were extracted for CQ2 of esophageal/pancreatic/colorectal cancer, respectively. The strength of evidence and recommendations were evaluated for CQ1 of colorectal cancer; however, we could not synthesize recommendations for other CQs owing to the lack of records. CONCLUSION: The use of G-CSF for primary prophylaxis in chemotherapy for colorectal cancer is inappropriate.

Compilation of regulations and procedures for monitoring filamentous fungi in hospital environments.

Air and surfaces in the hospital environment are a potential source of exposure to filamentous fungi (FF) that could cause invasive fungal diseases (IFD) in severely immunocompromised patients. The prevalent FF in IFD are species from the genera Aspergillus, Fusarium, Scedosporium, and those within the order Mucorales. We have compiled regulations and described the procedures used in the clinical mycology laboratory to assess the presence of FF in areas at risk for the development of IFD. The infection control committees of each establishment implement hospital policies to regulate and control processes aimed at preventing infections. Fungal load monitoring is an important step in this process to validate air quality in order to ensure a clean and protected environment for severely immunocompromised patients.

Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel.

BACKGROUND: Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity. OBJECTIVE: To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel. METHODS: We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild-type ELANE/G6PC3 were referred for next-generation sequencing. RESULTS: Sixty-five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman-Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte-colony stimulating factor or due to myeloid transformation. CONCLUSIONS: The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow-up.

A single arm Phase I/II trial on the combination of carboplatin, nab-paclitaxel and avastin as first-line treatment for advanced non-squamous non-small cell lung cancer (TORG1424/OLCSG1402: CARNAVAL).

BACKGROUND: Bevacizumab with platinum doublet therapy including paclitaxel + carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel + carboplatin led to Grade > 3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination in a Japanese population. METHODS: Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6 cycles of carboplatin (area under the concentration-time curve = 6 on Day 1) + nanoparticle albumin-bound paclitaxel (100 mg/m2 on Days 1, 8 and 15) + bevacizumab (15 mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel + bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial. RESULTS: The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42 months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade ≥ 3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%). CONCLUSIONS: All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

Analysis of maternal Fc gamma receptor IIIb isoantibodies using immunomagnetic negative selected neutrophils.

BACKGROUND AND OBJECTIVES: The isolation of neutrophils and subsequent detection of anti-human neutrophil antigens (HNA) antibodies are crucial in clinical medicine for the diagnosis of autoimmune neutropenia, neonatal alloimmune neutropenia (NAIN) and transfusion-related acute lung injury (TRALI). This study reports two cases of maternal anti-Fc-gamma-receptor-IIIb (FcγRIIIb) isoimmunization without NAIN symptoms and compares the efficiency of immunomagnetic negative selection (IMNS) with traditional dextran/Ficoll for neutrophil isolation in HNA serological assays. MATERIALS AND METHODS: Investigating two cases of maternal anti-FcγRIIIb isoimmunization, neutrophils from three donors were isolated from 8 mL of whole blood using IMNS and dextran/Ficoll. Serological assays included the granulocyte agglutination and immunofluorescence test, monoclonal antibody immobilization of granulocyte antigens and the LABScreen Multi (One Lambda). IMNS and dextran/Ficoll were compared in terms of cell yield, viability, time, cost and purity. RESULTS: Maternal anti-FcγRIIIb isoantibodies with FCGR3B gene deletion were detected in both cases. Newborns and fathers exhibited specific gene combinations: FCGR3B*02/FCGR3B*02 (Case 1) and FCGR3B*02/FCGR3B*03 (Case 2). IMNS outperformed dextran/Ficoll, yielding four times more neutrophils (average neutrophil counts: 18.5 × 103/µL vs. 4.5 × 103/µL), efficiently removing non-neutrophil cells and reducing processing time (30-40 min vs. 70-90 min), although it incurred a higher cost (2.7 times). CONCLUSION: Two cases of maternal anti-FcγRIIIb isoantibodies, unrelated to NAIN, were identified. Although neutropenia has not been described in these cases, we emphasize the importance of identifying asymptomatic cases with the potential for severe neutropenia. Additionally, IMNS is introduced as a rapid, high-yield, high-purity neutrophil isolation technique, beneficial for serological assays detecting anti-HNA antibodies.

Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses.

The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia. Accurate diagnosis is crucial for improved outcomes; however, diagnosis depends on familiarity with a heterogeneous group of rare disorders that remain incompletely characterised. The clinical and pathological overlap between reactive conditions, primary and congenital neutropenias, bone marrow failure, and myelodysplastic syndromes further clouds diagnostic clarity.We review the diagnostically useful clinicopathological and morphological features of reactive causes of neutropenia and the most common primary neutropenia disorders: constitutional/benign ethnic neutropenia, chronic idiopathic neutropenia, cyclic neutropenia, severe congenital neutropenia (due to mutations in ELANE, GFI1, HAX1, G6PC3, VPS45, JAGN1, CSF3R, SRP54, CLPB and WAS), GATA2 deficiency, Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome, Shwachman-Diamond Syndrome, the lysosomal storage disorders with neutropenia: Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes, Cohen, and Barth syndromes. We also detail characteristic cytogenetic and molecular factors at diagnosis and in progression to myelodysplastic syndrome/leukaemia.

Systematic review on efficacy and safety of empirical versus pre-emptive antifungal therapy among children with febrile neutropenia reveals paucity of data.

BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.

Can lithium be used in the setting of clozapine commencement in patients with COVID-19 associated neutropenia: A case report.

COVID-19 infection may increase the likelihood of neutropenia in patients already on clozapine. In clozapine treated patients experiencing COVID-19 associated neutropenia, adjunct therapy with lithium can be considered.

Granulocyte Transfusions in Neutropenic Infections: Insights From a Single-Center Study.

Introduction Despite the development of modern antibiotic and antifungal therapies, neutropenic infections remain life-threatening. Granulocyte transfusion (GTX) is a less frequently used treatment modality in patients with refractory neutropenic infections. The role of donor GTX remains controversial, partly because of the lack of proper clinical trials. This study aimed to contribute to the literature by evaluating the efficacy and side effects of granulocyte transfusions in our center. Methods Eight febrile neutropenic patients with confirmed infections received granulocyte transfusions from ABO-compatible related and unrelated donors. Donors received filgrastim and dexamethasone stimulation, and granulocyte suspensions were irradiated and administered within six hours. Monitoring, antibiotic therapy, and granulocyte colony-stimulating factor (G-CSF) support were maintained. Results Our study observed a 28-day survival rate of 25%, which was lower than that reported in previous literature. The median number of transfusions was 3, with an average eight-day duration post-infection diagnosis, and no side effects were observed. Conclusion While some patients benefited from GTX, overall survival rates remained modest, indicating the need for further research. Prospective, well-powered randomized controlled trials are essential to address patient selection, dosing, and duration to determine the clinical utility of GTX. This study underscores the complexity of GTX in real-world clinical practice and provides insight into the ongoing debate regarding its efficacy in treating severe neutropenic infections.

Haematological adverse effects associated with olanzapine in adolescents with anorexia nervosa: Three case reports.

OBJECTIVES: To describe haematological adverse effects in adolescents with anorexia nervosa who are taking olanzapine. METHODS: Case series report. CASE REPORT: The reported cases (two female patients and one male) were found to have blood test abnormalities after starting olanzapine and to rapidly recover their platelet and neutrophil values after the drug was discontinued. Low haemoglobin values persisted longer than observed in other series. These abnormalities became more noticeable when the dose of olanzapine was increased to 5 mg/day (initial dose 2.5 mg/day). It should be noted that two of the patients already had values indicative of mild neutropenia before they started the antipsychotic drug, and that these worsened as they continued taking the drug. In one of the patients there was only a decrease in neutrophil values, as well as mild anaemia. CONCLUSIONS: This first case series of haematological abnormalities in adolescents with anorexia nervosa who are taking olanzapine found values corresponding to pancytopenia in two of the three cases reported. It would be worthwhile to consider heightening haematological surveillance in this population when starting treatment with olanzapine and rethinking our knowledge regarding the frequency of these side effects.

Central Venous Catheter Consideration in Pediatric Oncology: A Systematic Review and Meta-analysis From the American Pediatric Surgical Association Cancer Committee.

BACKGROUND: Tunneled central venous catheters (CVCs) are the cornerstone of modern oncologic practice. Establishing best practices for catheter management in children with cancer is essential to optimize care, but few guidelines exist to guide placement and management. OBJECTIVES: To address four questions: 1) Does catheter composition influence the incidence of complications; 2) Is there a platelet count below which catheter placement poses an increased risk of complications; 3) Is there an absolute neutrophil count (ANC) below which catheter placement poses an increased risk of complications; and 4) Are there best practices for the management of a central line associated bloodstream infection (CLABSI)? METHODS: Data Sources: English language articles in Ovid Medline, PubMed, Embase, Web of Science, and Cochrane Databases. STUDY SELECTION: Independently performed by 2 reviewers, disagreements resolved by a third reviewer. DATA EXTRACTION: Performed by 4 reviewers on forms designed by consensus, quality assessed by GRADE methodology. RESULTS: Data were extracted from 110 manuscripts. There was no significant difference in fracture rate, venous thrombosis, catheter occlusion or infection by catheter composition. Thrombocytopenia with minimum thresholds of 30,000-50,000 platelets/mcl was not associated with major hematoma. Limited evidence suggests a platelet count <30,000/mcL was associated with small increased risk of hematoma. While few studies found a significant increase in CLABSI in CVCs placed in neutropenic patients with ANC<500Kcells/dl, meta-analysis suggests a small increase in this population. Catheter removal remains recommended in complicated or persistent infections. Limited evidence supports antibiotic, ethanol, or hydrochloric lock therapy in definitive catheter salvage. No high-quality data were available to answer any of the proposed questions. CONCLUSIONS: Although over 15,000 tunneled catheters are placed annually in North America into children with cancer, there is a paucity of evidence to guide practice, suggesting multiple opportunities to improve care. LEVEL OF EVIDENCE: III. This study was registered as PROSPERO 2019 CRD42019124077.

Individualized Treatment Approach for Rectal Adenocarcinoma in the Setting of Congenital Neutropenia.

Congenial neutropenia is a rare genetic disorder that puts individuals at risk of life-threatening bacterial infections early in life, and the current standard of care includes the use of colony-stimulating factors or curative intent bone marrow transplant. Cancer treatment strategies that include surgery, chemotherapy, radiation, and immunotherapy present significant challenges to an individual with a baseline immunodeficiency as seen in this condition. Evidence-based national guidelines aid physicians and patients in moving through complex cancer care regimens. However, these are altered when the intensity of the patient's comorbidities puts them at increased risk of developing a potentially life-threatening infection. Here, we present a patient treated for rectal carcinoma in the setting of severe congenital neutropenia.

Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection (RTI). METHODS: Prospective, multicenter, non-inferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus (RV), negative for a bacterial pathogen and had a favorable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with uneventful resolution, whereas the secondary endpoints were days of fever/hospitalization, requirement of antimicrobial treatment readministration, sepsis, pediatric intensive care unit (PICU) admission and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a RV as a unique identified microorganism, of which 139 had a favorable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p<0.001), with similar frequency of uneventful resolution (66/70 (94%) and 66/69 (96%), RR 1.01, (95% CI 0.93-1.09), absolute risk difference 0.01, (95% CI -0.05-0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, PICU admission or death were reported. CONCLUSIONS: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral RTI, based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

Neutrophil antigen antibodies affect engraftment and secondary graft failure in hematopoietic progenitor cell transplantation.

BACKGROUND: Research is limited on the role of antibodies against human neutrophil antigen (HNA) in hematopoietic progenitor cell (HPC) transplantation outcomes. STUDY DESIGN AND METHODS: A retrospective review was conducted on medical records of patients at the NIH Clinical Center enrolled in six research protocols. This case-control study included 21 patients tested for HNA antibodies from January 2010 to March 2022 who underwent HPC transplantation. In addition, 42 patients following the same research protocols were randomly selected as a control group. RESULTS: The cumulative incidence of time to neutrophil engraftment was significantly impacted by the patients' anti-HNA status (p = .042), with the patients with anti-HNA experiencing delayed engraftment. Secondary graft failure occurred in 4 out of 42 patients (9.52%; 95% confidence interval [CI]: 3.7-22.1) of the control group, while 5 out of 9 patients (55.5%; 95% CI: 26.7-81.1) with anti-HNA experienced secondary graft failure (p = .005). Furthermore, patients with anti-HNA had a lower proportion (p = .008 for full and p = .002 for partial chimerism) and cumulative incidence (p = .016 for full and p = .010 for partial chimerism) of achieving donor chimerism compared to the control group. DISCUSSION: The study reveals a potential link between anti-HNA and HPC transplantation outcomes not previously reported. Patients with anti-HNA had a lower proportion and cumulative incidence of achieving donor chimerism. Additionally, anti-HNA status affected the time for neutrophil engraftment, with a slower rate of neutrophil engraftment and increased risk of secondary failure in patients with anti-HNA.

Vancomycin-Induced Neutropenia With Subsequent Perioperative Readministration: A Case Report.

Vancomycin (VCM), an essential antibiotic for antimicrobial-resistant Gram-positive cocci, can lead to complications such as neutropenia. Here, we present a case of a 25-year-old male with noncommunicating hydrocephalus due to an intraventricular tumor who developed neutropenia during VCM therapy. Despite the suspected VCM-induced neutropenia, short-term readministration was deemed necessary for perioperative infection prophylaxis. This patient was readministered without neutropenia. A review of the literature revealed an earlier onset of VCM-induced neutropenia than that previously reported, emphasizing the importance of vigilant monitoring. Although readministration of VCM in patients with neutropenia is uncommon, it may be feasible with careful risk assessment, particularly in cases of mild neutropenia and short-term therapy. However, the mechanisms underlying VCM-induced neutropenia remain unclear, necessitating further research on the optimal management strategies.

The impact of myelosuppression on quality of life of patients treated with chemotherapy.

Side effects from chemotherapy-induced myelosuppression can negatively affect patients' quality of life (QoL). Neutropenia increases infection risk, and anemia frequently results in debilitating fatigue. Additionally, the bleeding risk associated with thrombocytopenia can lead to fear and anxiety. However, traditional interventions for myelosuppression fall short of the ideal. Granulocyte colony-stimulating factors reduce the risk of severe neutropenia but commonly lead to bone pain. Erythropoiesis-stimulating agents are not always effective and may cause thromboembolic events, while transfusions to correct anemia/thrombocytopenia are associated with transfusion reactions and volume overload. Trilaciclib, which is approved for reducing myelosuppression in patients with extensive-stage small cell lung cancer, together with several investigational agents in development for managing myelosuppression have the potential to improve QoL for patients on chemotherapy.

Chemotherapy can cause side effects by killing blood-forming cells in the bone marrow. This is known as myelosuppression and leads to neutropenia (decreased neutrophils [white blood cells]), anemia (decreased red blood cells) and thrombocytopenia (decreased platelets). Neutropenia can increase the risk of getting an infection, and severe cases might result in patients being hospitalized. Both neutropenia and anemia can cause fatigue, which is often reported by patients as being the most draining symptom of chemotherapy. Thrombocytopenia increases the risk of bleeding and can cause patients with cancer to become even more scared and anxious. Myelosuppression due to chemotherapy is usually managed with delays or reductions in the amount of chemotherapy that patients receive, but this may worsen the disease. Other treatments, known as supportive care interventions, include growth factors, which stimulate the production of blood cells and red blood cell or platelet transfusions. However, having these treatments in addition to chemotherapy can be a burden to patients, and they can cause side effects such as bone pain and blood clots. A treatment called trilaciclib is approved by the US Food and Drug Administration for patients receiving certain types of chemotherapy for advanced small-cell lung cancer. Trilaciclib has been shown to reduce neutropenia, anemia and thrombocytopenia in these patients and improve their quality of life. Other drugs are also being assessed in clinical trials for preventing or treating myelosuppression in patients with different cancer types. In the future, these drugs may improve quality of life for patients on chemotherapy.

The effect of leptin gene polymorphisms (LEP rs7799039 and LEPR rs1137101) on febrile neutropenia.

Background and aim: Leptin is mainly produced in adipose tissue and released into systemic circulation. Leptin and its receptor LEPR activate the Janus kinase/signal transducers and activators of transcription signaling cascade and increase cytokine discharge. In our study, we aimed to examine the role of leptin gene (LEP) rs7799039 and LEPR rs1137101 polymorphisms on the susceptibility for febrile neutropenia (FEN) attacks and their relationship with clinical findings during the course of FEN. Methods: This study included pediatric patients with a diagnosis of malignancy who applied to the pediatric emergency department between December 2019 and June 2022 and healthy controls. The genotypes of the LEP rs7799039 and LEPR rs1137101 genes were statistically compared between patients and healthy controls. In addition, the relationship between the genotype distribution of LEP rs7799039 and LEPR rs1137101 polymorphisms and clinical features during the course of FEN was investigated. Results: In the statistical analysis in terms of LEP rs7799039 and LEPR rs1137101 genotype distributions between the patient and healthy groups, there was no significant difference. Patients with the AA genotype of LEPR rs1137101 polymorphism had significantly more commonly a body mass index (BMI) value of <25, and all the patients with the AG/GG genotype had a BMI value of 25 and above. LEP rs7799039 and LEPR rs1137101 genotype distributions were not statistically significant with other clinical features. Conclusions: It was revealed that leptin gene polymorphisms did not have a significant effect during the course of FEN.

Risk factors for resistant gram-positive bacteremia in febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. METHODS: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. RESULTS: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. CONCLUSIONS: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.