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Journal of Infection in Developing... Feb 2024Patients with severe neutropenia who develop septic shock (SS) have high mortality. This study aimed to evaluate the risk factors and mortality of SS in patients with HM...
INTRODUCTION
Patients with severe neutropenia who develop septic shock (SS) have high mortality. This study aimed to evaluate the risk factors and mortality of SS in patients with HM and febrile neutropenia.
METHODOLOGY
We included all patients with hematological malignancies (HM) who presented fever and severe neutropenia, admitted to an oncological tertiary care center in Mexico City for one year.
RESULTS
Two hundred ninety-two episodes of fever and severe neutropenia were documented; 68 patients (23.2%) developed SS. Documented clinical infection was different between SS and non-SS patients (94.1% vs. 63.4%, p < 0.001); pneumonia was the most frequent infection (36.8% vs. 23.2%, p = 0.02). Also, in SS vs. non-SS, there were more positive cultures (69.1% vs. 38.4%, p < 0.001), higher frequency of Gram-negative bacteria (89.3% vs. 63.9%, p < 0.001), particularly Escherichia coli (68% vs. 44.2%) and Klebsiella spp. (23.4% vs. 15.1%). There were no differences when multidrug-resistant (MDR) microorganisms were compared. In the multivariate analysis, associated risk factors for SS were: prolonged neutropenia, a documented site of infection, and having received highly myelosuppressive chemotherapy. Risk factors for mortality at 30 days were: older patients, prolonged neutropenia, and SS.
CONCLUSIONS
Severe and prolonged neutropenia was associated with SS development and mortality at 30 days. ICU management should be offered to all critically ill patients with HM if long-term survival of the underlying malignancy is expected.
Topics: Humans; Shock, Septic; Hematologic Neoplasms; Neoplasms; Risk Factors; Escherichia coli; Febrile Neutropenia; Retrospective Studies
PubMed: 38484344
DOI: 10.3855/jidc.17451 -
JCO Global Oncology Mar 2024Sepsis 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...
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 ( = .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 ( ≤ .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.
Topics: Humans; Middle Aged; Sri Lanka; Retrospective Studies; Resource-Limited Settings; Neoplasms; Sepsis; Hematologic Neoplasms; Neutropenia
PubMed: 38484192
DOI: 10.1200/GO.23.00412 -
Frontiers in Immunology 2024Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients.
METHODS
PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs.
RESULTS
Fourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% . 54%, < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% . 18%, < 0.01; grade ≥ 3: 43% . 15%, < 0.01) and lymphopenia (any grade: 37% . 8%, < 0.01; grade ≥ 3: 31% . 8%, = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% . 66%, = 0.84; grade ≥ 3: 1% . 1%, = 0.36) and infections (any grade: 47% . 49%, = 0.86; grade ≥ 3: 24% . 20%, = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% . 2%, < 0.01) and lower risks of fatigue (any grade: 14% . 30%, < 0.01) and pyrexia (any grade: 14% . 29%, < 0.01).
CONCLUSION
This analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; B-Cell Maturation Antigen; Prospective Studies; Neurotoxicity Syndromes; Neutropenia
PubMed: 38482019
DOI: 10.3389/fimmu.2024.1348955 -
Frontiers in Immunology 2024Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in , impacting neutrophil maturation and leading to high risk of life-threatening...
Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in , impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT.
Topics: Humans; Child; Bone Marrow Transplantation; Congenital Bone Marrow Failure Syndromes; Busulfan; Hematopoietic Stem Cell Transplantation; Siblings; Prospective Studies; Neutropenia; Cyclophosphamide; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor
PubMed: 38469307
DOI: 10.3389/fimmu.2024.1369243 -
BMC Infectious Diseases Mar 2024Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of... (Review)
Review
Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.
Topics: Female; Humans; Adolescent; Leukemia, Myeloid, Acute; Candidiasis; Hematologic Neoplasms; Neutropenia
PubMed: 38448809
DOI: 10.1186/s12879-024-09172-9 -
Scientific Reports Mar 2024The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role...
The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a plethora of antibiotic-resistance genes play crucial role. However, the impact, predictive role and association of patient´s gut resistome in the course of the therapy is still to be elucidated. We analysed gut microbiota composition and resistome of 18 paediatric oncology patients undergoing hematopoietic stem cell transplantation, including 12 patients developing febrile neutropenia, hospitalized at The Bone Marrow Transplantation Unit of the National Institute of Children´s disease in Slovak Republic and healthy individuals (n = 14). Gut microbiome of stool samples obtained in 3 time points, before hematopoietic stem cell transplantation (n = 16), one week after hematopoietic stem cell transplantation (n = 16) and four weeks after hematopoietic stem cell transplantation (n = 14) was investigated using shotgun metagenome sequencing and bioinformatical analysis. We identified significant decrease in alpha-diversity and nine antibiotic-resistance genes msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia and aac(6)-Ii, one week after hematopoietic stem cell transplantation associated with febrile neutropenia. Multidrug-resistant opportune pathogens of ESKAPE, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli found in the gut carried the significant subset of patient's resistome. Over 50% of patients treated with trimethoprim/sulfamethoxazole, piperacillin/tazobactam and amikacin carried antibiotic-resistance genes to applied treatment. The alpha diversity and the resistome of gut microbiota one week after hematopoietic stem cell transplantation is relevant predictor of febrile neutropenia outcome after hematopoietic stem cell transplantation. Furthermore, the interindividual diversity of multi-drug resistant opportunistic pathogens with variable portfolios of antibiotic-resistance genes indicates necessity of preventive, personalized approach.
Topics: Child; Humans; Hematopoietic Stem Cell Transplantation; Biomarkers; Anti-Bacterial Agents; Escherichia coli; Febrile Neutropenia; Neoplasms
PubMed: 38448687
DOI: 10.1038/s41598-024-56242-8 -
La Tunisie Medicale Jul 2023In the era of genomics, orientation in the face of hereditary neutropenia still requires, first and foremost, a good clinical and cytological analysis. The thirty... (Review)
Review
In the era of genomics, orientation in the face of hereditary neutropenia still requires, first and foremost, a good clinical and cytological analysis. The thirty responsible genes now explain 60% of congenital neutropenia. These are rare since they are only found in 1‰ of all congenital neutropenia, estimated at 1% of the population. The clinical examination looks for phenotypes associated with syndromic hereditary neutropenia and cytology will guide this etiological research thanks to the data collected from blood count and bone marrow analysis. The objective of this narrative literature review is to provide an overview of the most recent literature regarding acquired and congenital chronic neutropenia and will provide a decision tree to guide towards aetiology. This will allow a better discussion with geneticists even if the genotype-phenotype correlation is not very strong.
Topics: Child; Humans; Neutropenia; Congenital Bone Marrow Failure Syndromes; Phenotype; Physical Examination
PubMed: 38445418
DOI: No ID Found -
Cureus Feb 2024The management of treatment-resistant schizophrenia (TRS) is challenging as the medications involved, often atypical antipsychotics, have a host of associated adverse...
The management of treatment-resistant schizophrenia (TRS) is challenging as the medications involved, often atypical antipsychotics, have a host of associated adverse effects. While complications such as agranulocytosis are well established and necessitate close hematological monitoring, the gastrointestinal effects of particular atypical antipsychotics, such as clozapine, are recognized to a lesser extent. The following case of TRS leading to chronic treatment-resistant pseudo-obstruction, eventually requiring total colectomy, highlights the considerable sequelae of clozapine on the gastrointestinal tract. Beyond the effects of severe constipation, the possible implications of ischemic colitis, stercoral perforation, and intraabdominal sepsis warrant a degree of caution when prescribing such medication. This study sheds light on the importance of monitoring bowel motility when administering antipsychotics, particularly clozapine, to avoid these deleterious consequences.
PubMed: 38435172
DOI: 10.7759/cureus.53377 -
Scientific Reports Mar 2024This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity....
This multicentre (22 centres in Turkey) retrospective cohort study aimed to assess the clinical outcomes of patients with neutropenic fever and SARS-CoV-2 positivity. Study period was 15 March 2020-15 August 2021. A total of 170 cases (58 female, aged 59 ± 15.5 years) that fulfilled the inclusion criteria were included in the study. One-month mortality rate (OMM) was 44.8%. The logistic regression analysis showed the following significant variables for the mentioned dependent variables: (i) achieving PCR negativity: receiving a maximum of 5 days of favipiravir (p = 0.005, OR 5.166, 95% CI 1.639-16.280); (ii) need for ICU: receiving glycopeptide therapy at any time during the COVID-19/FEN episode (p = 0.001, OR 6.566, 95% CI 2.137-20.172), the need for mechanical ventilation (p < 0.001, OR 62.042, 95% CI 9.528-404.011); (iii) need for mechanical ventilation: failure to recover from neutropenia (p < 0.001, OR 17.869, 95% CI 3.592-88.907), receiving tocilizumab therapy (p = 0.028, OR 32.227, 95% CI 1.469-707.053), septic shock (p = 0.001, OR 15.4 96% CI 3.164-75.897), and the need for ICU (p < 0.001, OR 91.818, 95% CI 15.360-548.873), (iv) OMM: [mechanical ventilation (p = 0.001, OR 19.041, 95% CI 3.229-112.286) and septic shock (p = 0.010, OR 5.589,95% CI 1.509-20.700)]. Although it includes a relatively limited number of patients, our findings suggest that COVID-19 and FEN are associated with significant mortality and morbidity.
Topics: Humans; Female; Retrospective Studies; Shock, Septic; COVID-19; SARS-CoV-2; Prognosis; Neutropenia
PubMed: 38433274
DOI: 10.1038/s41598-024-55886-w -
The Journal of Toxicological Sciences 2024This study was conducted as part of an investigation into the cause of vesnarinone-associated agranulocytosis. When HL-60 cells were exposed to vesnarinone for 48 hr,...
This study was conducted as part of an investigation into the cause of vesnarinone-associated agranulocytosis. When HL-60 cells were exposed to vesnarinone for 48 hr, little cytotoxicity was observed, although reduced glutathione (GSH) content decreased in a concentration-dependent manner. Significant cytotoxicity and reactive oxygen species (ROS) production were observed when intracellular GSH content was reduced by treatment with L-buthionine-(S, R)-sulphoximine. The involvement of myeloperoxidase (MPO) metabolism was suggested, as when HL-60 cells were exposed to a reaction mixture of vesnarinone-MPO/HO/Cl, cytotoxicity was also observed. In contrast, the presence of GSH (1 mM) protected against these cytotoxic effects. Liquid chromatography-mass spectrometry analysis of the MPO/HO/Cl reaction mixture revealed that vesnarinone was converted into two metabolites, (4-(3,4-dimethoxybenzoyl)piperazine [Metabolite 1: M1] and 1-chloro-4-(3,4-dimethoxybenzoyl)piperazine [Metabolite 2: M2]). M2 was identified as the N-chloramine form, a reactive metabolite of M1. Interestingly, M2 was converted to M1, which was accompanied by the conversion of GSH to oxidized GSH (GSSG). Furthermore, when HL-60 cells were exposed to synthetic M1 and M2 for 24 hr, M2 caused dose-dependent cytotoxicity, whereas M1 did not. Cells were protected from M2-derived cytotoxicity by the presence of GSH. In conclusion, we present the first demonstration of the cytotoxic effects and ROS production resulting from the MPO/HO/Cl metabolic reaction of vesnarinone and newly identified the causative metabolite, M2, as the N-chloramine metabolite of M1, which induces cytotoxicity in HL-60 cells. Moreover, a protective role of GSH against the cytotoxicity was revealed. These findings suggest a possible nonimmunological cause of vesnarinone agranulocytosis.
Topics: Humans; Chloramines; Glutathione; HL-60 Cells; Hydrogen Peroxide; Reactive Oxygen Species; Agranulocytosis; Antineoplastic Agents; Chlorides; Piperazines; Pyrazines; Quinolines
PubMed: 38432956
DOI: 10.2131/jts.49.95