Subject(s)
Acitretin , Ichthyosis, Lamellar , Keratolytic Agents , Neutropenia , Humans , Acitretin/adverse effects , Acitretin/therapeutic use , Ichthyosis, Lamellar/drug therapy , Keratolytic Agents/adverse effects , Keratolytic Agents/therapeutic use , Neutropenia/chemically induced , Infant , Male , FemaleABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Fluorouracil , Gastrointestinal Neoplasms , Neutropenia , Humans , Male , Female , Middle Aged , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , Gastrointestinal Neoplasms/drug therapy , Neutropenia/prevention & control , Neutropenia/chemically induced , Neutropenia/epidemiology , Adult , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Leucovorin/adverse effects , Irinotecan/therapeutic use , Irinotecan/adverse effects , Oxaliplatin/adverse effects , Oxaliplatin/therapeutic use , China/epidemiologyABSTRACT
BACKGROUND: Clozapine is known to cause agranulocytosis. Mandatory monitoring schemes are aimed at reducing the risk of agranulocytosis and of the consequences of agranulocytosis. All cases of agranulocytosis occurring in people prescribed clozapine are assumed to be caused by clozapine. METHODS: In a previous study, we examined a cohort of patients listed on our hospital database as having had clozapine-induced agranulocytosis and applied specific criteria to identify those with confirmed clozapine-related, life-threatening agranulocytosis. In this study, we examine the cases not meeting these specific criteria. RESULTS: In the original study, 9 of 23 cases met the criteria for clozapine-induced, life-threatening agranulocytosis. Of the 13 remaining cases for whom data were available, 5 were probably caused by clozapine but were not life-threatening. Three cases were the result of concomitant cancer chemotherapy. Three were anomalous results probably related to measurement error. For the remaining two cases, the cause was not identified. CONCLUSION: Not all cases of agranulocytosis occurring in people taking clozapine are caused by clozapine. The widely used threshold criterion-based diagnosis overestimates the risk of agranulocytosis. True clozapine-related agranulocytosis is best identified by pattern-based criteria: rapid fall in neutrophil counts over around 2 weeks to below 0.5 × 109/L for two consecutive days (unless clozapine is stopped very early or granulocyte colony stimulating factor is given) where other possible causes (benign ethnic neutropenia, cancer chemotherapy) can be ruled out.
Subject(s)
Agranulocytosis , Antipsychotic Agents , Clozapine , Neutropenia , Clozapine/adverse effects , Humans , Neutropenia/chemically induced , Antipsychotic Agents/adverse effects , Agranulocytosis/chemically induced , Male , Female , Adult , Middle AgedABSTRACT
BACKGROUND: Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients. METHODS: Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis. RESULTS: After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy. CONCLUSION: The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Doxorubicin , Glutathione S-Transferase pi , Glutathione Transferase , Paclitaxel , Polymorphism, Genetic , Humans , Glutathione Transferase/genetics , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Glutathione S-Transferase pi/genetics , Paclitaxel/adverse effects , Doxorubicin/adverse effects , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Prognosis , Genotype , Aged , Follow-Up Studies , Neutropenia/chemically induced , Neutropenia/geneticsABSTRACT
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.
Subject(s)
Adalimumab , Interleukin-17 , Interleukin-23 , Neutropenia , Psoriasis , Thalidomide , Humans , Adalimumab/adverse effects , Adalimumab/immunology , Psoriasis/drug therapy , Psoriasis/immunology , Female , Male , Neutropenia/chemically induced , Neutropenia/immunology , Neutropenia/epidemiology , Middle Aged , Japan , Adult , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Interleukin-23/antagonists & inhibitors , Interleukin-23/immunology , Thalidomide/adverse effects , Thalidomide/analogs & derivatives , Aged , Antibodies, Monoclonal, Humanized/adverse effectsABSTRACT
Combination checkpoint inhibitor (CPI) and chemotherapy is an effective and safe treatment strategy for patients with untreated classic Hodgkin lymphoma. Recent studies of programmed cell death protein 1 inhibitors combined with doxorubicin, vinblastine and dacarbazine have demonstrated high overall and complete response rates. This combination has a unique toxicity profile that should be managed appropriately so as not to compromise treatment efficacy. Common toxicities include rash, hepatoxicity, neutropenia and thyroid dysfunction. Here, we present four cases and the management strategies around such toxicities. In addition, we highlight key clinical decision-making around the administration of subsequent doses of CPI and chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Doxorubicin , Hodgkin Disease , Immune Checkpoint Inhibitors , Humans , Hodgkin Disease/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/administration & dosage , Male , Female , Adult , Doxorubicin/adverse effects , Doxorubicin/administration & dosage , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/therapeutic use , Middle Aged , Dacarbazine/adverse effects , Dacarbazine/administration & dosage , Neutropenia/chemically inducedABSTRACT
Levofloxacin prophylaxis during periods of neutropenia in pediatric hematopoietic stem cell transplant (HSCT) may reduce the number of febrile episodes and use of empiric intravenous antibiotics (EIA); however, the literature is conflicting. This retrospective review compared EIA use before and after implementation of levofloxacin prophylaxis at a children's hospital. Levofloxacin prophylaxis was associated with reduced use of certain EIA; however, did not reduce the number of positive blood cultures or clinical deteriorations. Therefore, levofloxacin prophylaxis may have implications for the stewardship of broad-spectrum intravenous antibiotics used in pediatric HSCT.
Subject(s)
Anti-Bacterial Agents , Antibiotic Prophylaxis , Hematopoietic Stem Cell Transplantation , Levofloxacin , Humans , Levofloxacin/therapeutic use , Levofloxacin/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Child , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Male , Female , Antibiotic Prophylaxis/methods , Child, Preschool , Adolescent , Infant , Neutropenia/chemically induced , Neutropenia/prevention & control , Administration, IntravenousABSTRACT
OBJECTIVES: This paper critiques the haematological monitoring guidelines for clozapine. It describes the history of clozapine, as well as the pathophysiology and epidemiology of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA). The paper appraises the extant literature on mandatory clozapine haematological monitoring. CONCLUSION: Contemporary Australian protocols for clozapine haematological monitoring are not consistent with the current evidence base. CIN and CIA are rare occurrences, and the associated risk of death is low. Potential modifications to existing guidelines include changing neutrophil thresholds for patients with benign ethnic neutropenia and reducing the frequency or removing haematological monitoring after two years of clozapine treatment.
Subject(s)
Agranulocytosis , Antipsychotic Agents , Clozapine , Drug Monitoring , Neutropenia , Clozapine/adverse effects , Clozapine/blood , Humans , Antipsychotic Agents/adverse effects , Agranulocytosis/chemically induced , Neutropenia/chemically induced , Drug Monitoring/methods , Australia , Practice Guidelines as TopicABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Fever of Unknown Origin , Neutropenia , Humans , Fever of Unknown Origin/drug therapy , Fever of Unknown Origin/etiology , Retrospective Studies , Male , Female , Child , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Child, Preschool , Neutropenia/chemically induced , Adolescent , Risk Factors , Infant , Febrile NeutropeniaABSTRACT
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.
Subject(s)
Fever , Hospitalization , Neutropenia , Humans , Male , Female , Retrospective Studies , Middle Aged , Fever/chemically induced , Fever/etiology , Neutropenia/chemically induced , Neutropenia/epidemiology , Hospitalization/statistics & numerical data , Adult , Aged , Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Hematologic Neoplasms/drug therapyABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic , Body Weight , Dog Diseases , Lymphoma , Vincristine , Animals , Dogs , Dog Diseases/chemically induced , Dog Diseases/drug therapy , Vincristine/adverse effects , Vincristine/therapeutic use , Vincristine/administration & dosage , Lymphoma/veterinary , Lymphoma/drug therapy , Retrospective Studies , Male , Female , Body Weight/drug effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/therapeutic use , Neutropenia/chemically induced , Neutropenia/veterinaryABSTRACT
Background: Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event associated with ATD but has also been reported as pre-treatment neutropenia in GD. Methods: We performed a retrospective cohort study to analyze the longitudinal clinical and biochemical data of 161 pediatric patients with GD who received either methimazole (MMI) or carbimazole (CBZ) as ATD. The inclusion criteria were elevated free thyroxine (fT4 >25 pmol/L), suppressed thyrotropin (TSH <0.05 mlU/mL), and elevated thyrotropin receptor antibodies (TSHRAbs >2.5 IU/L). Absolute neutrophil count (ANC) was used to define neutropenia (ANC <1800/µL) and agranulocytosis (ANC <500/µL). Results: Nine of the 161 patients had neutropenia at diagnosis (ANC: 1348/µL ± 250) without further deterioration under ATD. In this subgroup, we found higher levels of free triiodothyronine (fT3: 31.45 pmol/L ± 3.99) at diagnosis in comparison with those who developed neutropenia (26.29 pmol/L ± 12.96; p = 0.07) and those without neutropenia before and during therapy (23.12 pmol/L ± 13.7; p = 0.003). Thirty-eight patients (23.6%) became neutropenic (ANC: 1479/µL ± 262) while receiving ATD. Neutropenia occurred after a mean of 551.8 (range: 10-1376) days, mostly without further deterioration. Two of these 38 patients developed agranulocytosis and underwent emergency thyroidectomy. The patients with neutropenia were significantly younger (p = 0.031). Neutropenia occurred significantly more often in patients receiving CBZ (50%; n = 20/40) than in those receiving MMI (16.5%; n = 18/110; p = 0.001). The minimum ANC was significantly lower in the CBZ (1971/µL ± 1008) than in the MMI group (2546 ± 959); p = 0.004. Conclusions: Neutropenia occurred significantly more often under CBZ than MMI. As this is potentially due to higher immunogenicity, we suggest that children with GD should be treated with MMI. Frequent measurements of ANC may be needed to detect severe agranulocytosis, although low pre-treatment ANC may not necessarily be a contraindication to ATD treatment. Young age may be potentially associated with an increased risk of reduced ANC. Further investigation is necessary to fully understand risk factors for neutropenia in children with GD.
Subject(s)
Antithyroid Agents , Carbimazole , Graves Disease , Methimazole , Neutropenia , Humans , Methimazole/adverse effects , Methimazole/therapeutic use , Child , Neutropenia/chemically induced , Neutropenia/blood , Antithyroid Agents/adverse effects , Antithyroid Agents/therapeutic use , Female , Male , Retrospective Studies , Graves Disease/drug therapy , Graves Disease/blood , Adolescent , Carbimazole/therapeutic use , Carbimazole/adverse effects , Child, Preschool , Agranulocytosis/chemically induced , Thyroxine/therapeutic use , Thyroxine/blood , Thyrotropin/blood , Triiodothyronine/bloodABSTRACT
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.
Subject(s)
Acute Lung Injury , Aminopyridines , Benzamides , Cyclopropanes , Disease Models, Animal , Lipopolysaccharides , Neutropenia , Phosphodiesterase 4 Inhibitors , Animals , Aminopyridines/pharmacology , Cyclopropanes/pharmacology , Cyclopropanes/therapeutic use , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Lipopolysaccharides/adverse effects , Mice , Benzamides/pharmacology , Benzamides/therapeutic use , Neutropenia/drug therapy , Neutropenia/chemically induced , Phosphodiesterase 4 Inhibitors/pharmacology , Cytokines/metabolism , Male , Bronchoalveolar Lavage Fluid , Neutrophils/drug effects , Neutrophils/metabolismABSTRACT
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.
Subject(s)
Azathioprine , Cat Diseases , Filgrastim , Neutropenia , Animals , Cats , Filgrastim/therapeutic use , Filgrastim/adverse effects , Cat Diseases/drug therapy , Cat Diseases/chemically induced , Azathioprine/therapeutic use , Azathioprine/adverse effects , Neutropenia/veterinary , Neutropenia/chemically induced , Neutropenia/drug therapy , Medication Errors/veterinary , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Male , Methimazole/adverse effects , Methimazole/therapeutic use , FemaleABSTRACT
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.
Subject(s)
Granulocyte Colony-Stimulating Factor , Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Remission Induction , Practice Guidelines as Topic , Induction Chemotherapy , Japan , Neutropenia/chemically induced , Neutropenia/prevention & controlABSTRACT
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.
Subject(s)
Doxorubicin/analogs & derivatives , Neoplasms , Neutropenia , Pneumonia , Humans , Cardiotoxicity/drug therapy , Bayes Theorem , Doxorubicin/adverse effects , Liposomes , Neoplasms/drug therapy , Neutropenia/chemically induced , Pneumonia/drug therapy , Polyethylene GlycolsABSTRACT
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.
Subject(s)
Anemia , Malnutrition , Mucositis , Neoplasms , Neutropenia , Humans , Child , Child, Preschool , Prospective Studies , Ghana/epidemiology , Malnutrition/complications , Malnutrition/epidemiology , Malnutrition/diagnosis , Hospitals, Teaching , Anthropometry/methods , Neoplasms/complications , Neoplasms/drug therapy , Arm/anatomy & histology , Anemia/chemically induced , Anemia/epidemiology , Neutropenia/chemically induced , Neutropenia/epidemiologyABSTRACT
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.
Subject(s)
Hematologic Neoplasms , Neoplasms , Neutropenia , Sepsis , Humans , Middle Aged , Sri Lanka/epidemiology , Retrospective Studies , Resource-Limited Settings , Neoplasms/complications , Sepsis/therapy , Sepsis/drug therapy , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Neutropenia/chemically induced , Neutropenia/diagnosis , Neutropenia/complicationsABSTRACT
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 (125â mg/m2: GG type; 100â mg/m2: GA type; 75â 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 (4.8â m vs 4.9â m vs 4.4â m; p = 0.5249) and OS (9.3â m vs 9.3â 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.