Safety of empirical antibiotic therapy discontinuing for fever of unknown origin during high-risk neutropenia in children.

BACKGROUND: ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72 h of treatment and at least 24-48 h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia. MATERIAL AND METHODS: We retrospectively included all consecutive FUO episodes occurring during profound neutropenia ≥ 10 days in children in our institution. We evaluated the safety of EAT discontinuation in patients for whom the ECIL guidelines were followed compared to those for whom they didn't. We used a combined criterion of mortality and intensive care unit admission at 30 days. We identified risk factors for recurrent fever after EAT discontinuation. RESULTS: Fifty-one FUO episodes occurred in 37 patients. EAT discontinuation followed ECIL guidelines in 19 (37 %) episodes. No deaths and-or transfers in ICU occurred in the ECIL group. The duration of EAT was shorter by nine days in the group following ECIL guidelines (p < 0.001). We observed 14 (27 %) episodes of recurrent fever. Mucositis was significantly associated with recurrent fever (p < 0.01). CONCLUSION: EAT discontinuation seems feasible and safe in FUO during prolonged febrile neutropenia in children. However, mucosal lesions should prompt thorough surveillance due to the risk of recurrent fever.

Causes and outcomes of non-chemotherapy induced neutropenic fever in hospitalized adults: An observational study.

Neutropenic fever in adults undergoing chemotherapy for cancer treatment is a medical emergency and has been the focus of numerous studies. However, there is a paucity of data about non-chemotherapy induced neutropenic fever (non-CINF). We retrospectively reviewed 383 adults with neutropenic fever hospitalized at one academic medical center between October 2015 and September 2020 to characterize the frequency, causes, and outcomes of non-CINF. Twenty-six percent of cases of neutropenic fever were non-chemotherapy induced. Among these, the major causes of neutropenia were hematologic malignancy, infection, and rheumatologic disease, and the major causes of fever were infections. Patients with non-CINF had a higher 30-day mortality than those with chemotherapy induced neutropenic fever (25% vs 13%, P = .01). Non-CINF constituted > 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.

Filgrastim Use in the Treatment of Azathioprine-Induced Myelosuppression Toxicity After Prescription Error in the Feline.

Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats.

The Effect of Roflumilast on Lipopolysaccharide-induced Acute Lung Injury During Neutropenia Recovery in Mice.

BACKGROUND/AIM: Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier breakdown in sepsis is lipopolysaccharide (LPS), which is a component of the outer membrane of gram-negative bacterial cell walls. Maintaining increased cyclic adenosine monophosphate (cAMP) levels in endothelial cells is effective in preventing endothelial dysfunction and microvascular permeability. The aim of this study was to elucidate whether roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor, is effective in LPS-induced acute lung injury (ALI) during neutropenia recovery in a murine model. MATERIALS AND METHODS: To induce neutropenia, all mice were administered intraperitoneal cyclophosphamide. On day 2 after neutropenia, mice were administered LPS by intra-tracheal instillation. In the prevention group, roflumilast was given orally on day 0, when neutropenia was induced. In the treatment group, roflumilast was administered orally 1 hour after LPS injection. RESULTS: Roflumilast attenuated histopathological changes associated with LPS-induced lung injury. The accumulation of neutrophils and the concentrations of inflammatory cytokines IL-1ß, TNF-α, and IL-6 in bronchoalveolar lavage fluids were inhibited effectively by roflumilast. Also, MMP-9 and TGF-ß expression was attenuated in the roflumilast group. CONCLUSION: Roflumilast significantly attenuated LPS-induced ALI during neutropenia recovery.

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.

Short-term chemotherapy-related complications and undernutrition in children diagnosed with cancer at Korle Bu Teaching Hospital, Accra, Ghana: A prospective cohort study.

Undernutrition in children with cancer is associated with complications during cancer therapy. The study objective was to determine the association between specific anthropometric parameters and short-term chemotherapy-related complications and mortality. This was a hospital-based, prospective cohort study of children, age ≤12 years, with a new cancer diagnosis at the Paediatric Oncology Unit, Korle Bu Teaching Hospital, Ghana. Socio-demographic information, cancer characteristics and anthropometric measurements were obtained at enrolment. Participants were followed up for twelve weeks from commencement of chemotherapy and selected treatment-related complications such as anaemia and thrombocytopenia requiring transfusions, prolonged neutropenia resulting in treatment delays, febrile neutropenia, mucositis and death were recorded. A total of 133 participants were recruited with a median age of 4.5 years. Eighty-one (60.9%) were diagnosed with solid tumours, 31 (23.3%) had leukaemias and 21 (15.8%) had lymphomas. Of the anthropometric parameters assessed, only arm anthropometry using upper arm muscle area (UAMA) and mid-upper arm circumference (MUAC) were associated with complications. Participants with wasting were more likely to develop anaemia and mucositis. However, the incidence of prolonged neutropenia was significantly higher among participants with average UAMA (p = 0.043) and low average UAMA (p = 0.049) compared to those with low UAMA. Risk of neutropenia was also significantly less among those with wasting by MUAC compared to those well-nourished (p = 0.045). Twenty-three participants (17.3%) died with a greater proportion (11/44; 25%) occurring in those who were wasted using MUAC. These findings underscore the need for nutritional surveillance at diagnosis and during chemotherapy, particularly where co-morbid disease is prevalent.

Effectiveness and safety of primary prophylaxis with G-CSF after induction therapy for acute myeloid leukemia: a systematic review and meta-analysis of the clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology.

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications.

A real-world analysis of FDA Adverse Event Reporting System (FAERS) events for liposomal and conventional doxorubicins.

The clinical application of conventional doxorubicin (CDOX) was constrained by its side effects. Liposomal doxorubicin was developed to mitigate these limitations, showing improved toxicity profiles. However, the adverse events associated with liposomal doxorubicin and CDOX have not yet been comprehensively evaluated in clinical settings. The FAERS data from January 2004 to December 2022 were collected to analyze the adverse events of liposomal doxorubicin and CDOX. Disproportionate analysis and Bayesian analysis were employed to quantify this association. Our analysis incorporated 68,803 adverse event reports related to Doxil/Caelyx, Myocet and CDOX. The relative odds ratios (RORs, 95%CI) for febrile neutropenia associated with CDOX, Doxil/Caelyx, and Myocet were 42.45 (41.44; 43.48), 17.53 (16.02; 19.20), and 34.68 (26.63; 45.15) respectively. For cardiotoxicity, they were 38.87(36.41;41.49), 17.96 (14.10; 22.86), and 37.36 (19.34; 72.17). For Palmar-Plantar Erythrodysesthesia (PPE), the RORs were 6.16 (5.69; 6.68), 36.13 (32.60; 40.06), and 19.69 (11.59; 33.44). Regarding onset time, significant differences adverse events including neutropenia, PPE, pneumonia and malignant neoplasm progression. This study indicates that clinical monitoring for symptoms of cardiotoxicity of CDOX and Myocet, and PPE and interstitial lung disease of Doxil should be performed. Additionally, the onset time of febrile neutropenia, malignant neoplasm progression, and pneumonia associated with Doxil and Myocet merits particular attention. Continuous surveillance, risk evaluations, and additional comparative studies between liposomal doxorubicin and CDOX were recommended.

Successful Management of Neutropenic Sepsis Is Key to Better Survival of Patients With Blood Cancer in Sri Lanka: Real-World Data From the Resource-Limited Setting.

PURPOSE: Sepsis is the main cause of nonrelapse mortality, and there are no published data on applicability of supportive care protocols from high-income countries such as Sri Lanka. The aim of the study was to investigate management and mortality of neutropenic episodes among Hemato-Oncology patients. MATERIALS AND METHODS: Retrospective analysis of clinical characteristics, management, morbidity, and mortality of neutropenic Hemato-Oncology patients presented to the Lanka Hospital Blood Cancer Centre from January 1, 2019 to December 31, 2019 was performed. RESULTS: A total of 169 neutropenic episodes were identified; 115 (68%) of such episodes were related to chemotherapy. Acute leukemia, lymphoproliferative disorders, and plasma cell disorders accounted for 23%, 69%, and 8% of patients, respectively. The median age of patients who had sepsis was 56 years, whereas that of those who had no sepsis was 53 years (P = .49). The median time to neutropenia was 9 days for those in the sepsis group compared with 8 days in the group that had no sepsis (0.64). The median neutrophil count in the group that had sepsis was 0.06, whereas it was 0.69 in the group that had no sepsis (P ≤ .05). The median time to commencement of antibiotics was 20 minutes. CONCLUSION: To our knowledge, this is the only documented study related to outcome and successful applicability of western supportive care protocols to Sri Lankan patients with neutropenia. In this study, we have shown that neutropenic sepsis can be successfully managed in the setting of limited resources with service development, following guidelines and staff training.

Individual Irinotecan Therapy Under the Guidance of Pre-Treated UGT1A1*6 Genotyping in Gastric Cancer.

Background: Severe delayed diarrhea and hematological toxicity limit the use of irinotecan. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a critical enzyme in irinotecan metabolism. The study aims to investigate the safety and efficacy of irinotecan under the guidance of the pre-treatment UGT1A1 genotype in the second-line treatment of gastric cancer. Methods: This study involved 110 patients. Irinotecan was injected intravenously every 3 weeks, and the dose of irinotecan was determined by polymorphism of the UGT1A1 gene, which was divided into three groups (125 mg/m2: GG type; 100 mg/m2: GA type; 75 mg/m2: AA type). The primary end point was overall survival (OS), the secondary end points were progression-free survival (PFS) and safety. Results: One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Among 107 patients, there were no significant differences in PFS (4.8 m vs 4.9 m vs 4.4 m; p = 0.5249) and OS (9.3 m vs 9.3 m vs NA; p = 0.6821) among patients with GG/GA/AA subtypes after dose adjustment. For the patient with homozygosity mutation, treatment was switched to paclitaxel. There were no significant differences in PFS and OS among patients with different alleles or after dose adjustment (p > 0.05). There was a significant difference in the risk of delayed diarrhea (p = 0.000), leukopenia (p = 0.003) and neutropenia (p = 0.000) in patients with different UGT1A1*6 genotypes, while no difference in patients with different UGT1A1*28 genotypes. Additionally, grade 3/4 diarrhea, neutropenia, and leukopenia were significantly more common in AA genotype patients compared to GG (2%, 19%, 24%) or GA (23%, 31%, 31%) genotype patients. Conclusion: Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.

Model-Based Prediction of Irinotecan-Induced Grade 4 Neutropenia in Cancer Patients: Influence of Incorporating Germline Genetic Factors in the Model.

Neutropenia is the major dose-limiting toxicity of irinotecan-based therapy. The objective of this study was to assess whether inclusion of germline genetic variants into a population pharmacokinetic/pharmacodynamic model can improve prediction of irinotecan-induced grade 4 neutropenia and identify novel variants of clinical value. A semimechanistic population pharmacokinetic/pharmacodynamic model was used to predict neutrophil response over time in 197 patients receiving irinotecan. Covariate analysis was performed for demographic/clinical factors and 4,781 genetic variants in 84 drug response- and toxicity-related genes to identify covariates associated with neutrophil response. We evaluated the predictive value of the model for grade 4 neutropenia reflecting different clinical scenarios of available data on identified demographic/clinical covariates, baseline and post-treatment absolute neutrophil counts (ANCs), individual pharmacokinetics, and germline genetic variation. Adding 8 genetic identified covariates (rs10929302 (UGT1A1), rs1042482 (DPYD), rs2859101 (HLA-DQB3), rs61754806 (NR3C1), rs9266271 (HLA-B), rs7294 (VKORC1), rs1051713 (ALOX5), and ABCB1 rare variant burden) to a model using only baseline ANCs improved prediction of irinotecan-induced grade 4 neutropenia from area under the receiver operating characteristic curve (AUC-ROC) of 50-64% (95% confidence interval (CI), 54-74%). Individual pharmacokinetics further improved the prediction to 74% (95% CI, 64-84%). When weekly ANC was available, the identified covariates and individual pharmacokinetics yielded no additional contribution to the prediction. The model including only ANCs at baseline and at week 1 achieved an AUC-ROC of 78% (95% CI, 69-88%). Germline DNA genetic variants may contribute to the prediction of irinotecan-induced grade 4 neutropenia when incorporated into a population pharmacokinetic/pharmacodynamic model. This approach is generalizable to drugs that induce neutropenia and ultimately allows for personalized intervention to enhance patient safety.

Gut microbiome in association with chemotherapy-induced toxicities among patients with breast cancer.

BACKGROUND: Little research has focused on the relationship between gut microbiome and chemotherapy-induced toxicity. METHODS: This prospective study involves 301 patients with breast cancer who had prechemotherapy stool samples collected. Gut microbiome was sequenced by shotgun metagenomics; associations with chemotherapy-induced toxicities during first-line treatment by gut microbial diversity, composition, and metabolic pathways with severe (i.e., grade ≥3) hematological and gastrointestinal toxicities were evaluated via multivariable logistic regression. RESULTS: High prechemotherapy α-diversity was associated with a significantly reduced risk of both severe hematological toxicity (odds ratio [OR] = 0.94; 95% CI, 0.89-0.99; p = .048) and neutropenia (OR = 0.94; 95% CI, 0.89-0.99; p = .016). A high abundance of phylum Synergistota, class Synergistia, and order Synergistales were significantly associated with a reduced risk of severe neutropenia; conversely, enrichment of phylum Firmicutes C, class Negativicutes, phylum Firmicutes I, and class Bacilli A, order Paenibacillales were significantly associated with an increased risk of severe neutropenia (p range: 0.012-2.32 × 10-3; false discovery rate <0.1). Significant positive associations were also observed between severe nausea/vomiting and high Chao1 indexes, ß-diversity (p < .05), 20 species belonging to the family Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae (p value range: 6.14 × 10-3 to 1.33 × 10-5; false discovery rate <0.1), and three metabolic pathways involved in reductive tricarboxylic acid cycle I and cycle II, and an incomplete reductive tricarboxylic acid cycle (p < .01). Conversely, a high abundance of species Odoribacter laneus and the pathway related to the L-proline biosynthesis II were inversely associated with severe nausea/vomiting. CONCLUSIONS: Our study suggests that gut microbiota may be a potential preventive target to reduce chemotherapy-induced toxicity.

A population pharmacokinetic model for posaconazole intravenous solution and oral powder for suspension formulations in pediatric patients with neutropenia.

The objective of this study was to support posaconazole dose regimens in pediatric patients aged ≥2 years, using a population pharmacokinetic (PK) approach with data from a phase 1b study (NCT02452034). A one-compartment model with first-order absorption was fit to pharmacokinetic data from 144 participants aged 2 to 17 years, who were administered posaconazole as intravenous (IV) and powder for oral suspension (PFS) formulations, or IV only, at dosing regimens of 3.5, 4.5, and 6 mg/kg. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final model simulated posaconazole exposure in patients aged 2 to <7 and 7 to 17 years at dosing regimens of 4.5, 6, and 7.5 mg/kg. Plasma concentration data following IV and PFS administration were well-described by a one-compartment model with first-order absorption and estimated bioavailability, where clearance and volume were subject to allometric scaling by body weight. The 6-mg/kg dosing regimen achieved the pharmacokinetic target (90% of the pediatric population having an average steady-state plasma concentration of ≥500 and <2,000 ng/mL) for both age groups, regardless of whether patients received IV and PFS or IV only. In a virtual adolescent population (body weight >40 kg), the 300 mg/day posaconazole tablet was also predicted to achieve the pharmacokinetic target and remain within a safe range of exposure. These data informed a weight-based nomogram for PFS dosing to maximize the number of pediatric patients achieving the pharmacokinetic target across weight bands, while also maintaining a favorable benefit/risk profile.

Filgrastim biosimilar (EP2006): A review of 15 years' post-approval evidence.

Filgrastim is approved for several indications, including reduction of the incidence and duration of chemotherapy-induced neutropenia and for stem cell mobilization. The filgrastim biosimilar, EP2006, has been available in Europe since 2009, and in the United States since 2015. In this time, preclinical and clinical data used to support the approval of EP2006 have been published. These data established the biosimilarity of EP2006 to reference filgrastim in terms of structure, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Additional real-world evidence studies have also demonstrated equivalent efficacy and safety of EP2006 compared with reference filgrastim, both in the reduction of neutropenia and in stem cell mobilization in clinical practice. This review summarizes these preclinical, clinical, and real-world data, as well as the available cost-effectiveness data, for EP2006 since its approval 15 years ago.

The Effect of Galantamine on Lipopolysaccharide-induced Acute Lung Injury During Neutropenia Recovery in Mice.

BACKGROUND/AIM: Acute lung injury (ALI) is associated with a high mortality rate and cancer patients who receive chemotherapy are at high risk of ALI during neutropenia recovery. Galantamine is a cholinesterase inhibitor used for Alzheimer's disease treatment. Previous studies have shown that galantamine reduced inflammatory response in lipopolysaccharide (LPS)-induced ALI in rats. Mer protein was negatively associated with inflammatory response. The aim of the study was to investigate whether galantamine is effective in LPS-induced ALI during neutropenia recovery and its effect on Mer tyrosine kinase (MerTK) expression in mice. MATERIALS AND METHODS: Intraperitoneal cyclophosphamide was given to mice to induce neutropenia. After 7 days, LPS was administered by intratracheal instillation. Intraperitoneal galantamine was given once before LPS administration and in another group, galantamine was given twice before LPS administration. RESULTS: Galantamine attenuated LPS-induced ALI in histopathological analysis. The neutrophil percentage was lower in the group where galantamine was injected once, compared to the LPS group (p=0.007). MerTK expression was also higher in the group where galantamine was injected once but did not reach statistical significance (p=0.101). CONCLUSION: Galantamine attenuated inflammation in LPS-induced ALI during neutropenia recovery.

Comparative overall survival of CDK4/6 inhibitors in combination with endocrine therapy in advanced breast cancer.

Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer.

PURPOSE: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. METHODS: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. RESULTS: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. CONCLUSION: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

PURPOSE: Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. METHODS: This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. RESULTS: Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION: These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.

Efficacy and safety of nanoparticle albumin-bound paclitaxel in taxane-pretreated metastatic breast cancer patients.

BACKGROUND: Taxanes are the basic components of breast cancer chemotherapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows improved antitumor effects because of more targeted delivery. However, the effects of nab-paclitaxel have not been systematically studied in patients with metastatic breast cancer (MBC) pretreated with taxanes. Considering the limited treatment options for MBC, this study retrospectively evaluated the clinical efficacy and adverse effects of nab-paclitaxel in patients with taxane-pretreated MBC. METHODS: Patients who had previously received taxanes and subsequently received nab-paclitaxel chemotherapy for MBC at Jiangsu Cancer Hospital between October 2014 and April 2022 were included for analysis. The primary end point was progression-free survival (PFS), and the secondary end points were the objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and side effects. RESULTS: A total of 236 female patients with MBC were included. The median PFS was 7.20 months (95% confidence interval [CI], 6.63-7.80 months), and the ORR, DCR, and CBR were 29.55% (95% CI, 23.50%-35.60%), 83.64% (95% CI, 78.70%-88.60%), and 56.36% (95% CI, 49.80%-63.00%), respectively. Following nab-paclitaxel treatment, the median PFS of patients who were sensitive to taxanes during previous treatments was significantly longer than that of patients who were resistant to taxanes (7.57 months vs. 4.43 months, p < .001). The most common adverse events were sensory neuropathy (89.83%), neutropenia (48.73%), leukopenia (46.61%), and anemia (35.59%). CONCLUSION: Nab-paclitaxel demonstrated clinical activity in taxane-pretreated patients with MBC. This beneficial effect was observed both in patients who were sensitive and resistant to taxanes during previous treatments. These results suggest nab-paclitaxel as the preferred chemotherapy regimen in patients with MBC, regardless of their sensitivity to taxanes during previous treatments.

Incidence of valganciclovir-related leukopenia and neutropenia in solid organ transplant recipients at high risk of cytomegalovirus disease.

BACKGROUND: Valganciclovir (VGCV) prophylaxis is associated with an increased risk of hematologic side effects. We analyzed the impact of VGCV prophylaxis on leukopenia and neutropenia rates and explored risk factors for its occurrence. METHODS: Retrospective cohort study of adult cytomegalovirus (CMV)-seronegative solid organ transplantation (SOT) recipients of either CMV-seropositive (CMV D+/R-) or CMV-seronegative (CMV D-/R-) donors between July 2005 and March 2019. CMV D+/R- SOT recipients received 3-12 months of VGCV prophylaxis whereas CMV D-/R- SOT recipients received no VGCV prophylaxis. Competing risk regression was used to calculate risk factors for significant neutropenia (neutrophil count < 1000/µL). RESULTS: A total of 430 CMV-seronegative SOT recipients (median age of 52.1 years, 76.5% males) were included, of which 203 (47.2%) were CMV D+/R- and 227 (52.8%) CMV D-/R-. The unadjusted incidence rate ratio of significant neutropenia attributable to VGCV exposure in the first year post-transplant was 13.50 (95% confidence interval 7.36-27.11). Acute rejection occurred more frequently in neutropenic patients at 32.5% compared to 19.1% in those without neutropenia (p = .033). On multivariate analysis, VGCV prophylaxis for 1-90 days and 91-180 days versus no VGCV were the strongest risk factors for significant neutropenia with a sub-distribution hazard ratio of 39.6 (95% CI, 8.57-182.6) and 13.2 (95% CI, 5.46-32.0), respectively. CONCLUSIONS: VGCV prophylaxis is limited by high rates of neutropenia. Future prospective studies are needed to assess alternative CMV prophylactic strategies in SOT recipients.