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PURPOSE: We aimed at identifying prevalence, clinical outcomes and prognostic factors in cancer patients with intravenous chemotherapy-induced severe neutropenia (ICISN). METHODS: In this multicenter retrospective cohort study on the clinical data warehouse of Greater Paris University Hospitals (AP-HP), we included all adult patients with solid cancer hospitalized between 2016 and 2021 with intravenous chemotherapy within 30 days prior to severe neutropenia (D70 or D611 ICD-10 codes AND a neutrophil count < 500/mm3). The primary endpoint was referral to intensive care unit (ICU) or death within 30 days. We collected cancer, patient, and treatment characteristics. RESULTS: Among 141,586 cancer inpatients, 40,660 received chemotherapy among whom 661 (1.6%) had ICISN. Median age was 63 years (interquartile range (IQR), 54-70) and 330 patients (49%) were female. The median Charlson score was 10 (IQR, 8-11). Main primary cancers were lung (n = 204, 31%) and breast (n = 87, 13%). Advanced cancers were found in 551 patients (83%), 331 (50%) were in 1st line of chemotherapy, 284 (42%) in the 1st cycle of the current line and 149 (22%) had primary G-CSF. Documented bacterial (mostly gram-negative bacilli) and fungal infections were observed in 113 (17%) and 19 (3%) patients; 58 (9%) were transferred to ICU and 82 (12%) died within 30 days, 372 (56%) patients received subsequent chemotherapy. Independent prognostic factors were the level of monocyte, lymphocyte counts or albuminemia and a documented bacterial infection, while Charlson index and primary prophylactic G-CSF were not associated with patient clinical outcomes. CONCLUSION: Despite the use of primary G-CSF, ICISN remains a frequent event, which leads to ICU death in one on five cases Some prognostic factors of severity have been highlighted and could help clinicians to prevent severe complications.
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Antineoplásicos , Neoplasias , Neutropenia , Humanos , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Masculino , Anciano , Neoplasias/tratamiento farmacológico , Prevalencia , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios de Cohortes , Pronóstico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Administración IntravenosaRESUMEN
BACKGROUND: Trilaciclib, in comparison to placebo plus carboplatin, etoposide, ± atezolizumab (PEA), has shown significant reductions in incidence of severe neutropenia (SN) among patients with extensive-stage small cell lung cancer (ES-SCLC). Despite these findings, real-world utility remains limited. METHODS: A single-center quasi-experimental study compared trilaciclib + PEA (PEAT) versus PEA in ES-SCLC patients. The study period ranged from April 1, 2021 to July 31, 2022, for the PEAT recipients and February 1, 2020, to February 28, 2021, for PEA recipients. The primary endpoint evaluated was incidence of SN after cycle 1 and during the treatment period. Secondary endpoints included measures related to myelopreservation and patient outcomes. RESULTS: Among 34 PEAT and 44 PEA patients, baseline characteristics were similar, except for a higher median age (69 vs 64 years) and more males (64.7% vs 38.6%) in the PEAT cohort. The PEAT cohort exhibited a lower SN rate (3%) versus the PEA cohort (18%), with statistical significance demonstrated on multivariate analysis (p = 0.015). Additionally, the PEAT cohort also demonstrated significant reductions in red blood cell transfusion requirements (3% vs 23%; p = 0.02), grade 3-4 anemia (6% vs 25%; p = 0.03), and grade 3-4 thrombocytopenia (0% vs 11%, p = 0.045). CONCLUSION: Trilaciclib, in combination with PEA, demonstrated an improvement in the safety profile without compromising survival outcomes in ES-SCLC patients. These findings underscore the potential benefits of incorporating trilaciclib in real-world clinical settings for enhanced patient care.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Estadificación de Neoplasias , Pirimidinas , PirrolesRESUMEN
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.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Neoplasias Gastrointestinales , Neutropenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Neoplasias Gastrointestinales/tratamiento farmacológico , Neutropenia/prevención & control , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Adulto , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Leucovorina/efectos adversos , Irinotecán/uso terapéutico , Irinotecán/efectos adversos , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , China/epidemiologíaRESUMEN
BACKGROUND: Concern about clozapine-associated neutropenia contributes to clozapine's underutilization and racial disparities in access. People with African ancestry are more likely to have lower normative absolute neutrophil counts (ANC), associated with the Duffy null genetic polymorphism. Recent data on clozapine-associated neutropenia in the US are lacking. METHODS: Patients prescribed clozapine in the Johns Hopkins Medicine electronic medical record (EMR) between 2013 and 2023 were identified. Duffy null Associated Neutrophil Count (DANC) was assigned if there were two ANC's < 2000 cells/µL, >30 days apart, before starting clozapine. Rates of neutropenia, timing of first neutropenia, and demographic differences were explored. RESULTS: 974 received clozapine and had ANC's available, with 63.9 % male, 51.1 % White, and 39 % Black. 287 were presumed to start clozapine during the study period, and were 62.4 % male, 46 % White, and 44.9 % Black. No patients developed severe neutropenia. 59 (6.1 %) developed mild or moderate neutropenia. 19 (6.6 %) new starts had presumed DANC, and none developed neutropenia. 11 of 16 presumed new starts who developed neutropenia did so within eight months. No demographic differences were found between groups for presumed new starts. For non-new starts, where DANC assignment was not possible, Black patients were more likely than White patients to develop neutropenia (OR 3.48, 95 % CI [1.65, 7.73]). DISCUSSION: To our knowledge, this is the first observational study of clozapine-associated neutropenia in the US in the past decade, and it includes a substantial proportion of Black patients. ANC monitoring requirements may be too strict, contributing to clozapine underutilization.
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Antipsicóticos , Clozapina , Neutropenia , Humanos , Clozapina/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Masculino , Femenino , Adulto , Antipsicóticos/efectos adversos , Persona de Mediana Edad , Estados Unidos , Negro o Afroamericano , Población Blanca , Factores de Tiempo , Recuento de Leucocitos , Esquizofrenia/tratamiento farmacológico , Adulto Joven , Sistema del Grupo Sanguíneo Duffy/genética , AncianoRESUMEN
BACKGROUND: To evaluate the risk of neutropenia during treatment with anti-IL-23 antibodies in patients with psoriasis. METHOD: We conducted an observational study with cohort design using MID-NET® in Japan. We identified patients with psoriasis who were newly prescribed anti-IL-23 antibodies, anti-IL-17-antibodies, adalimumab, or apremilast between January 1, 2009, and March 31, 2021. We estimated the adjusted hazard ratio (aHR) of anti-IL-23 antibodies compared to that of anti-IL-17 antibodies, adalimumab, or apremilast, for the risk of grade 2 (neutrophil count < 1,500/µL) or grade 3 (neutrophil count < 1,000/µL) neutropenia. RESULTS: Overall, 287 patients on anti-IL-23 antibodies, 189 patients on anti-IL-17 antibodies, 293 patients on adalimumab, and 540 patients on apremilast were included. Compared with anti-IL-17 antibodies, the aHR (95% confidence interval (CI)) of anti-IL-23 antibodies was 0.83 (0.27-2.51) for grade 2 and 0.40 (0.02-7.60) for grade 3 neutropenia; that when compared with adalimumab was 0.76 (0.28-2.06) for grade 2 but was not calculated for grade 3 as no cases were found; and that compared with apremilast was 3.88 (0.62-24.48) for grade 2 and 0.43 (0.02-11.63) for grade 3 neutropenia. CONCLUSION: No clear increase in the risk of neutropenia with anti-IL-23 antibodies was observed.
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Adalimumab , Interleucina-17 , Interleucina-23 , Neutropenia , Psoriasis , Talidomida , Humanos , Adalimumab/efectos adversos , Adalimumab/inmunología , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Femenino , Masculino , Neutropenia/inducido químicamente , Neutropenia/inmunología , Neutropenia/epidemiología , Persona de Mediana Edad , Japón , Adulto , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunología , Interleucina-23/antagonistas & inhibidores , Interleucina-23/inmunología , Talidomida/efectos adversos , Talidomida/análogos & derivados , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversosRESUMEN
Aim: There is limited data available regarding the comparison of Sacituzumab govitecan (SG) vs. chemotherapy in metastatic breast cancer patients.Materials & methods: We performed a systematic review and meta-analysis aimed to assess the safety profile of SG vs. chemotherapy for metastatic breast cancer (mBC) clinical trials.Results: The pooled odds ratio for outcomes such as grade 3-4 and all grade neutropenia, leukopenia, anemia and other non-hematological adverse events showed a higher risk for patients receiving SG. No statistically significant differences were reported in terms of grade 3-4 fatigue, all grade nausea, febrile neutropenia and treatment discontinuation due to adverse events.Conclusion: Our data, coupled with a statistically and clinically meaningful survival benefit, support the use of SG for mBC.
[Box: see text].
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Camptotecina , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/efectos adversos , Camptotecina/administración & dosificación , Inmunoconjugados , Metástasis de la Neoplasia , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Few studies have evaluated the post-endoscopic adverse events in patients with neutropenia and thrombocytopenia. Current guidelines do not provide clear direction on this topic. AIM: We explore the pooled rates of safety and adverse effects of endoscopic interventions in thrombocytopenia and neutropenia patients via a systematic review & meta-analysis. METHODS: Databases, including Medline, Scopus, and Embase, were searched (in May 2023) using specific terms for studies evaluating the clinical outcomes of endoscopy in patients with thrombocytopenia and neutropenia. Standard meta-analysis methods were employed using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. RESULTS: Six studies and four studies evaluated endoscopic outcomes in patients with thrombocytopenia and neutropenia respectively with mean age was 56 years. The pooled rate of total post-biopsy bleeding and total post-polypectomy bleeding among patients with thrombocytopenia was 4% (95% CI 1-11), I2 = 84%, and 12% (95% CI 3-36) I2 = 43%. The total rate of post procedure-related bleeding in thrombocytopenia was 5% (95% CI 1-14) I2 = 95%. The pooled rate of post-endoscopic infection (fever from any cause, bacteremia) in neutropenia was 10% (95% CI 3-28%) I2 = 96%. On sub analysis, the pooled rate of bacteremia and 30 days all-cause mortality in neutropenia was 4% (95% CI 3-5%) I2 = 0% and 13% (95% CI 4-34%) I2 = 95% respectively. CONCLUSION: Our data supports the notion that endoscopic procedures are safe for neutropenic, thrombocytopenic patients with suitable indications and reasonable functional status and have an acceptable risk/benefit ratio.
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Neutropenia , Trombocitopenia , Humanos , Trombocitopenia/epidemiología , Neutropenia/epidemiología , Endoscopía Gastrointestinal/efectos adversos , Endoscopía Gastrointestinal/métodos , Persona de Mediana EdadRESUMEN
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%, Pâ =â .01). Non-CINF constitutedâ >â 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.
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Fiebre , Hospitalización , Neutropenia , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Fiebre/inducido químicamente , Fiebre/etiología , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Hospitalización/estadística & datos numéricos , Adulto , Anciano , Neoplasias/tratamiento farmacológico , Antineoplásicos/efectos adversos , Neoplasias Hematológicas/tratamiento farmacológicoRESUMEN
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.
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Síndromes Congénitos de Insuficiencia de la Médula Ósea , Mutación , Neutropenia , Humanos , Neutropenia/genética , Neutropenia/congénito , Neutropenia/epidemiología , Neutropenia/diagnóstico , Masculino , Israel/epidemiología , Femenino , Niño , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Síndromes Congénitos de Insuficiencia de la Médula Ósea/diagnóstico , Preescolar , Adolescente , Predisposición Genética a la Enfermedad , Adulto , Trasplante de Células Madre Hematopoyéticas , Lactante , Consanguinidad , Glucosa-6-Fosfatasa/genética , Alelos , Sistema de Registros , Secuenciación de Nucleótidos de Alto Rendimiento , Adulto Joven , Fenotipo , Estudios de Asociación GenéticaRESUMEN
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.
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Anemia , Desnutrición , Mucositis , Neoplasias , Neutropenia , Humanos , Niño , Preescolar , Estudios Prospectivos , Ghana/epidemiología , Desnutrición/complicaciones , Desnutrición/epidemiología , Desnutrición/diagnóstico , Hospitales de Enseñanza , Antropometría/métodos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Brazo/anatomía & histología , Anemia/inducido químicamente , Anemia/epidemiología , Neutropenia/inducido químicamente , Neutropenia/epidemiologíaRESUMEN
Hematologic abnormalities are common manifestations of SLE, although neutropenia is observed less frequently and is not included in the classification criteria. Nonetheless, neutropenia is a risk factor for infections, especially those caused by bacteria or fungi. We aimed to evaluate the impact of neutropenia in SLE through a systematic investigation of all infections in a large cohort of well-characterized patients, focusing on neutropenia, lymphopenia, and hypocomplementemia. Longitudinal clinical and laboratory parameters obtained at visits to the Rheumatology Unit, Linköping University Hospital, and linked data on all forms of healthcare utilization for all the subjects included in our regional SLE register during 2008-2022 were assessed. Data regarding confirmed infections were retrieved from the medical records. Overall, 333 patients were included and monitored during 3,088 visits to a rheumatologist during the study period. In total, 918 infections were identified, and 94 occasions of neutropenia (ANC < 1.5 × 109/L) were detected in 40 subjects (12%). Thirty neutropenic episodes in 15 patients occurred in association with infections, of which 13 (43%) required in-hospital care, 4 (13%) needed intensive care, and 1 (3%) resulted in death. Bayesian analysis showed that patients with ≥ 1 occasion of neutropenia were more likely to experience one or more infections (OR = 2.05; probability of association [POA] = 96%). Both invasiveness (OR = 7.08; POA = 98%) and severity (OR = 2.85; POA = 96%) of the infections were significantly associated with the present neutropenia. Infections are common among Swedish SLE patients, 12% of whom show neutropenia over time. Importantly, neutropenia is linked to both the invasiveness and severity of infections. Awareness of the risks of severe infections in neutropenic patients is crucial to tailor therapies to prevent severe illness and death.
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Lupus Eritematoso Sistémico , Neutropenia , Humanos , Prevalencia , Suecia/epidemiología , Teorema de Bayes , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Neutropenia/epidemiología , Neutropenia/complicacionesRESUMEN
BACKGROUND: Valganciclovir is approved for cytomegalovirus prophylaxis in pediatrics using the Pescovitz algorithm. There are reports of valganciclovir overdoses in children with low body surface area and overestimated creatinine clearance utilizing this algorithm. This study compared the incidence of neutropenia and cytomegalovirus infection between the Pescovitz and weight-based dosing algorithms. METHODS: A single-center retrospective chart review from January 2010 to September 2018 was performed on pediatric heart, liver, and kidney transplant recipients, who received valganciclovir. Data were collected from the initiation of valganciclovir prophylaxis to 30 days after discontinuation. The primary objective was the incidence of neutropenia in patients receiving valganciclovir dosed by the Pescovitz versus weight-based dosing algorithms. RESULTS: This study included 187 pediatric transplant recipients who received valganciclovir dosed via the Pescovitz (62 recipients) or weight-based dosing algorithms (125 recipients). The incidence of neutropenia was higher in the Pescovitz (69.4%) compared to the weight-based dosing group (53.6%; p = .04) including moderate and severe neutropenia. Cytomegalovirus viremia was not significantly different between the two groups and occurred in 4.8% of the Pescovitz group compared to 2.4% of the weight-based group (p = .4). CONCLUSIONS: The incidence of neutropenia was greater in recipients receiving valganciclovir dosed via the Pescovitz algorithm compared to the weight-based dosing. There were no significant differences in regard to cytomegalovirus viremia or disease between the two groups.
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Infecciones por Citomegalovirus , Neutropenia , Trasplante de Órganos , Humanos , Niño , Valganciclovir/uso terapéutico , Antivirales/efectos adversos , Estudios Retrospectivos , Receptores de Trasplantes , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Neutropenia/epidemiología , Neutropenia/etiología , Viremia/tratamiento farmacológico , Ganciclovir/efectos adversosRESUMEN
OBJECTIVE: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. METHODS: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. RESULTS: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. CONCLUSION: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.
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Neutropenia , Centros de Atención Terciaria , Humanos , Neutropenia/epidemiología , Estudios Retrospectivos , Niño , Masculino , Femenino , Preescolar , Centros de Atención Terciaria/estadística & datos numéricos , Adolescente , Lactante , Prevalencia , Enfermedad Crónica , Brasil/epidemiología , Enfermedades Autoinmunes/epidemiología , Recuento de LeucocitosRESUMEN
Neutropenia can be caused by a variety of congenital and acquired factors, with Chemotherapy-induced myelosuppression being the most common cause. Neutropenia significantly affects oral health, leading to the manifestation of oral lesions such as ulcers, fungal and viral infections, and mucositis. This study aims to investigate oral lesions in patients with hematological malignancies who developed neutropenia after chemotherapy. This cross-sectional study included 50 patients with hematological malignancies. The participants were divided into 2 groups: the first group consisted of 25 patients with hematological malignancies who developed chemotherapy-induced neutropenia and the second group consisted of 25 patients with hematological malignancies who did not develop chemotherapy-induced neutropenia. Patients were assigned to one of the groups based on the absolute neutrophil count (ANC). Full oral clinical examination was performed to determine the presence of oral lesions. In the Chemotherapy-Induced Neutropenia group, the most common lesion was ulceration, observed in 12 patients (48%). Fungal infections were the second most common, present in 5 patients (20%), followed by viral infections in 4 patients (15%), and mucositis, which occurred in a single patient (4%). A statistically significant association was found between neutropenia and the presence of oral ulcers (P valueâ =â .015). In contrast, in the Chemotherapy group, oral changes were less frequent. Fungal infections were the most common, occurring in 4 patients (15%), followed by oral mucositis in 3 patients (12%). Ulceration and viral infections were the least common, each observed in 1 patient (4%). The frequency of various forms of oral ulcers increases with the severity of neutropenia. However, there was no significant increase in other oral lesions in patients with neutropenia.
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Antineoplásicos , Neoplasias Hematológicas , Mucositis , Micosis , Neutropenia , Úlceras Bucales , Virosis , Humanos , Estudios Transversales , Mucositis/inducido químicamente , Úlceras Bucales/tratamiento farmacológico , Siria , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Neutropenia/complicaciones , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Micosis/tratamiento farmacológico , Antineoplásicos/efectos adversos , Virosis/complicacionesRESUMEN
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.
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Infecciones por Citomegalovirus , Neutropenia , Trasplante de Órganos , Adulto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Valganciclovir/efectos adversos , Citomegalovirus , Incidencia , Antivirales/efectos adversos , Estudios Retrospectivos , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/tratamiento farmacológico , Neutropenia/epidemiología , Neutropenia/inducido químicamente , Trasplante de Órganos/efectos adversos , Ganciclovir/efectos adversos , Receptores de TrasplantesRESUMEN
BACKGROUND: CDK4/6 inhibitors (CDK4/6i) have shown great efficacy in prolonging progression-free survival and is the current standard of care for hormone positive (HR(+)) metastatic breast cancer (mBC). Despite well tolerability and ease of use, the most common side effect of CDK4/6i is myelosuppression, with neutropenia the most prevalent adverse effect. Studies show that the prevalence and severity of neutropenia are more marked in Asian patients, although details remain obscure. METHODS: In this study, we retrospectively analyzed 105 Taiwanese patients who received palbociclib for HR(+) HER2(-) mBC at the Taipei Veterans General Hospital. To investigate a possible genetic association for high prevalence of neutropenia, we queried the Taiwan Biobank with publicly available germline databases (ALFA, gnomAD, ExAC, 1000 Genomes project, HapMap), for the allele frequencies of 4 neutropenia-related SNPs (ABCB1_rs1045642, ABCB1_rs1128503, ERCC1_rs3212986, ERCC1_rs11615) and compared between different ethnicities. In addition, one of the patients was a long-term patient with peritoneal dialysis. We quantified the levels of palbociclib in her serum and peritoneal fluid by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Interestingly, in our cohort, early neutropenia nadir (occurred within 56 days of start) was associated with worse treatment outcome, while occurrence of grade 3/4 neutropenia was associated with better outcome. We observed an extremely high incidence of neutropenia (96.2% any grade, 70.4% grade 3/4). In the analyzed germline databases, we discovered a higher SNP frequency of the T allele in ABCB1_rs1128503, a lower frequency of T allele in ABCB1_rs1045642, and a higher SNP frequency of G allele in ERCC1_rs11615. We observed that palbociclib levels in peritoneal dialysate ranged from around 20-50 ppb, and serum levels reached 100-110 ppb during drug administration and decreased to <10 ppb during discontinuation. CONCLUSION: Our retrospective analysis of real world palbociclib use reveals an association with grade 3/4 neutropenia with better outcome and early neutropenia nadir with worse outcome. Our findings of Asian specific SNPs support a predisposition toward profound and prevalent neutropenia in Asian patients under CDK4/6i. We also report the first pharmacokinetics analysis on a patient with peritoneal dialysis receiving CDK4/6i. In summary, our study provides novel clinical and genotypic insights into CDK4/6i associated neutropenia.
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Neoplasias de la Mama , Neutropenia , Piperazinas , Piridinas , Femenino , Humanos , Estudios Retrospectivos , Prevalencia , Receptor ErbB-2/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Neutropenia/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quinasa 4 Dependiente de la CiclinaRESUMEN
BACKGROUND: Clozapine is associated with the risk of serious neutropenia. However, this risk might decrease over time, meaning that indefinite absolute neutrophil count (ANC) monitoring could be unnecessary. We aimed to determine the epidemiology and timing of clozapine-associated neutropenia outcomes, to investigate variables that might contribute to the odds of neutropenia, and to determine risk of competing neutropenic events during clozapine treatment. METHODS: We performed a retrospective analysis of the Australian and New Zealand Viatris Pharmacovigilance system (one of two monitoring databases for these two countries) between June 6, 1990, and Oct 25, 2022. Patients were excluded from analysis if they commenced clozapine before 1990, did not have a haematology test within 2 weeks of commencement date, or had no follow-up. We measured minor neutropenia (ANC 1·0-1·5 × 109 per L) and serious neutropenia (ANC <1·0 × 109 per L) leading to cessation of clozapine within 6 weeks of the neutropenic event. We determined the rates of minor and serious neutropenia and calculated odds ratios (ORs) for the likelihood of neutropenia leading to cessation. For serious neutropenia leading to cessation, we used time-to-event to calculate rolling weekly averages and to perform competing risk analysis of outcomes using Cox proportional hazards models and a Fine-Gray subdistribution hazards regression model. For the subset of data where information on previous clozapine use was available, we did an analysis for participants who did and did not have previous clozapine exposure. FINDINGS: We included 26 630 people, with 2·6 million ANC values. Within the total cohort, 17 585 people (66%) were male, 9025 (33·9%) female, and 20 (0·1%) other gender, and the mean age was 36·1 years (SD 13·7). We did not have data on race or ethnicity. Of the 26 630 people taking clozapine, 1146 (4·3%) had minor neutropenia, 313 (1·2%) had serious neutropenia leading to cessation, and 223 (0·8%) had serious neutropenia unrelated to clozapine without cessation. In people with no previous exposure to clozapine (n=15 973), the cumulative incidence of serious neutropenia leading to cessation was 0·9% at 18 weeks and 1·4% at 2 years; the weekly incidence rate for serious neutropenia leading to cessation peaked at 9 weeks (0·128%) and fell to a rolling average weekly incidence of 0·001% by 2 years. For minor neutropenia, the cumulative incidence was 1·7% at 18 weeks and 3·5% at 2 years; the weekly incidence rate peaked at 9 weeks (0·218%) and fell to a stable rolling average of 0·01%. The median time to a serious neutropenic event leading to cessation was 17 weeks (IQR 9·96-102). Previous clozapine exposure reduced the risk of serious neutropenia leading to cessation (OR 0·19, 95% CI 0·12-0·31; p <0·0001). INTERPRETATION: Most serious neutropenia leading to clozapine cessation occurs within 18 weeks of treatment and becomes negligible after 2 years. Weekly haematological monitoring after the first 18 weeks could be safely reduced to once every 4 weeks and ceased after 2 years unless clinically indicated. Clozapine retrial after interruption with 2 cumulative years of unremarkable testing might not require further haematological monitoring. A serious neutropenia ANC threshold of ≤1·0 × 109 per L could be used in more jurisdictions. FUNDING: None.
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Antipsicóticos , Clozapina , Neutropenia , Humanos , Masculino , Femenino , Adulto , Clozapina/efectos adversos , Estudios Retrospectivos , Antipsicóticos/efectos adversos , Nueva Zelanda/epidemiología , Australia/epidemiología , Neutropenia/inducido químicamente , Neutropenia/epidemiologíaRESUMEN
Importance: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer. Objective: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV. Design, Setting, and Participants: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023. Exposure: HIV infection detected before or within 90 days of participants' breast cancer diagnosis. Main Outcomes and Measures: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests. Results: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]). Conclusions and Relevance: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.
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Neoplasias de la Mama , Infecciones por VIH , Neutropenia , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Cohortes , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neutropenia/inducido químicamente , Neutropenia/epidemiologíaRESUMEN
Importance: Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited. Objective: To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia. Design, Setting, and Participants: This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023. Exposure: All patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/µL. Main Outcomes and Measures: The primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC <1000/µL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia. Results: A total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/µL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (ß = -2356 [95% CI, -4120.6 to -611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (ß = -4056 [95% CI, -7003.6 to -1344.5]; adjusted R2 = 0.251; P = .006). Conclusions and Relevance: In this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.
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Neutropenia , Neoplasias de la Retina , Retinoblastoma , Femenino , Humanos , Niño , Lactante , Retinoblastoma/tratamiento farmacológico , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/etiología , Melfalán/administración & dosificación , Topotecan/administración & dosificación , Incidencia , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Neutropenia/tratamiento farmacológico , Infusiones Intraarteriales/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Clozapine is a very effective therapeutic option for schizophrenic disorders that have been refractory to most other therapies. This extremely positive aspect clashes easily with an adverse effect of the drug that is deemed to be a very dangerous one: agranulocytosis. We asked whether the mandatory strict hematological follow-up prescribed in the black box warning of clozapine's label is proportioned to the actual incidence of agranulocytosis, considering that is the main reason that such a drug is often used only late in the treatment course. METHODS: We carried out a systematic review of reports examining clozapine administration and agranulocytosis incidence. We specifically selected those where mild and moderate neutropenia was not used as a trigger to stop administration of clozapine, to better estimate the sheer incidence of agranulocytosis when clozapine was continued even with mild hematological effect, where detected. We used PubMed, MEDLINE, EMBASE, Cochrane, and ScienceDirect databases to identify clinical studies conducted between January 1975 and April 2023. RESULTS: We included 14 studies, mostly retrospective ones, that examined the incidence of hematological adverse effects in patients using clozapine. A total of 2354 subjects were included. The mean age of the subjects was 33.5 years. The mean duration of observation of subjects who took clozapine was 800 days, with a mean daily dose of 319.5 mg per day. Of the 2354 subjects examined, we found that 11 of them experienced agranulocytosis (0.47%). CONCLUSIONS: These results suggest the evidence of a lower incidence of agranulocytosis than previously estimated and are in line with more recent meta-analyses. We may therefore think that clinical practice may demand a revision of the approach that both psychiatrists and supervising organizations often take when talking about clozapine.