ABSTRACT
Among immunocompromised hosts, leukemia patients, and hematopoietic cell transplant recipients are particularly vulnerable, facing challenges in balancing coronavirus disease 2019 (COVID-19) management with their underlying conditions. In this How I Treat article, we discuss how we approach severe acute respiratory syndrome coronavirus 2 infections in daily clinical practice, considering the existing body of literature and for topics where the available data are not sufficient to provide adequate guidance, we provide our opinion based on our clinical expertise and experience. Diagnostic approaches include nasopharyngeal swabs for polymerase chain reaction testing and chest computed tomography scans for symptomatic patients at risk of disease progression. Preventive measures involve strict infection control protocols and prioritizing vaccination for both patients and their families. Decisions regarding chemotherapy or hematopoietic cell transplantation in leukemia patients with COVID-19 require careful consideration of factors such as COVID-19 severity and treatment urgency. Treatment protocols include early initiation of antiviral therapy, with nirmatrelvir/ritonavir or remdesivir. For cases of prolonged viral shedding, distinguishing between viable and non-viable viruses remains challenging but is crucial for determining contagiousness and guiding management decisions. Overall, individualized approaches considering immune status, clinical presentation, and viral kinetics are essential for effectively managing COVID-19 in leukemia patients.
Subject(s)
Adenosine Monophosphate , Alanine , Antiviral Agents , COVID-19 , Hematopoietic Stem Cell Transplantation , Immunocompromised Host , Leukemia , SARS-CoV-2 , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , COVID-19/complications , Antiviral Agents/therapeutic use , Leukemia/complications , Leukemia/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , COVID-19 Drug Treatment , Ritonavir/therapeutic use , Transplant Recipients , Lopinavir/therapeutic use , Virus Shedding , Drug CombinationsABSTRACT
Schizophrenia (SCZ) and schizoaffective disorder (SHZ) are psychiatric disorders commonly identified in individuals in their late adolescence or early adulthood. Comorbidities are common, though a concurrent diagnosis of leukemia, one of the most frequently occurring cancers of adolescence, has not yet been described in such cases. This case study outlines the clinical presentation, course, and treatment response of two 17-year-old male adolescents whose psychotic disorders complicated their leukemia treatment. The first patient was diagnosed with leukemia and subsequently with SCZ while undergoing leukemia treatment. The second patient was diagnosed with SHZ prior to the onset of leukemia. The case study will follow the methodology of Robert E. Stake (Abma & Stake, 2014), as the two cases share a leukemia diagnosis and the reported mental health impact connected with cancer-directed treatment. Early identification and treatment are critical for both psychotic disorders and cancers, often impacting the long-term prognosis. However, when co-occurring, their interplay can present unique challenges to care.
Subject(s)
Psychotic Disorders , Humans , Male , Psychotic Disorders/psychology , Adolescent , Schizophrenia/complications , Leukemia/psychology , Leukemia/complications , Leukemia/therapyABSTRACT
The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality.
Subject(s)
Antifungal Agents , Fusariosis , Fusarium , Humans , Fusariosis/drug therapy , Fusariosis/microbiology , Fusarium/isolation & purification , Aged , Adult , Antifungal Agents/therapeutic use , Middle Aged , Female , Male , Aged, 80 and over , Young Adult , Adolescent , Brazil/epidemiology , Child , Japan/epidemiology , Child, Preschool , Leukemia, Myeloid, Acute/complications , United States/epidemiology , Leukemia/complications , Leukemia/microbiology , Dermatomycoses/microbiology , Dermatomycoses/epidemiology , Dermatomycoses/drug therapy , Dermatomycoses/pathologyABSTRACT
Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.
Subject(s)
Leukemia , Lymphoma , Thyroid Neoplasms , Humans , Male , Female , Middle Aged , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/pathology , Germany/epidemiology , Retrospective Studies , Aged , Lymphoma/epidemiology , Leukemia/epidemiology , Leukemia/complications , Adult , Incidence , Risk Factors , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/etiologyABSTRACT
Herpes zoster (HZ) is rare in healthy children, but more prevalent in those with leukemia. Optimal timing of chemotherapy reinitiation after HZ treatment is challenging because chemotherapy suppresses immunity and increases risk of HZ relapse. We aimed to optimize the timing of chemotherapy reinitiation after HZ therapy in children with leukemia. The study included 31 children with acute leukemia and HZ infection. General information, clinical symptoms, laboratory test results, duration of HZ treatment, and prognosis were compared with those of children with leukemia alone. Correlation analysis was performed for 20 children who restarted chemotherapy after HZ treatment. Of 31 children with leukemia and HZ, 67.74% had lesions at multiple sites. The median time from chemotherapy initiation to HZ onset was 14.1 (1.5-29.5) months. Among 27 children included in the follow-up, there was one case of HZ relapse. After excluding children who did not continue chemotherapy after HZ treatment, the median interval between completion of HZ therapy and chemotherapy reinitiation in the remaining 20 children was 8.00 (- 3 to 27) days. Lymphocyte counts (LY#) on restarting chemotherapy correlated inversely with HZ lesion healing time (p < 0.05). LY# at the time of HZ onset were lower than those pre- and post-onset, and lower than those in the control group (p < 0.05). In conclusion, children with leukemia have a good HZ prognosis, but an increased risk of HZ recurrence. LY# at the time of chemotherapy reinitiation may be a useful indicator for selecting the optimal interval between antiviral therapy completion and chemotherapy reinitiation.
Subject(s)
Antiviral Agents , Herpes Zoster , Leukemia , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Herpes Zoster/drug therapy , Leukemia/drug therapy , Leukemia/complications , Lymphocyte Count , Prognosis , Retrospective Studies , Time FactorsABSTRACT
BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) in leukemia patients progresses rapidly with high mortality. Limited data are available on imaging studies in this population. The study aims to develop prediction models for 7-day and short-term mortality risk based on the non-contrast computed tomography (NCCT) image features. METHODS: The NCCT image features of ICH in 135 leukemia patients between 2007-2023 were retrospectively extracted using manual assessment and radiomics methods. After multiple imputation of missing laboratory data, univariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Random forest models were built with comprehensive evaluation and ranking of feature importance. RESULT: 135 and 129 patients were included in the studies for 7-day and short-term prognostic models, respectively. The median age of all enrolled patients was 35 years, and there were 86 male patients (63.7 %). Clinical models (validation: AUC [area under the curve] = 0.78, AUPRC [area under the precision-recall curve] = 0.73; AUC = 0.84, AUPRC = 0.86), radiomics models (validation: AUC = 0.82, AUPRC = 0.78; AUC = 0.75, AUPRC = 0.77), and the combined models (validation: AUC = 0.84, AUPRC = 0.83; AUC = 0.87, AUPRC = 0.89) predicted 7-day and short-term mortality with good predictive efficacy. Clinical decision curve analysis showed that the combined models predicted 7-day and 30-day risk of death would be more beneficial than other models. Shape features contributed significantly more than semantic features in both radiomics models and combined models (93.3 %, 52.1 %, as well as 85.2 %,37.4 %, respectively) for 7-day and 30-day mortality. CONCLUSIONS: Combined models constructed based on NCCT perform well in predicting the risk of 7-day and short-term mortality in ICH patients with leukemia. Shape features extracted by radiomics are important markers for modeling the prognosis.
Subject(s)
Cerebral Hemorrhage , Leukemia , Machine Learning , Tomography, X-Ray Computed , Humans , Male , Female , Adult , Tomography, X-Ray Computed/methods , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/complications , Leukemia/complications , Leukemia/diagnostic imaging , Retrospective Studies , Prognosis , Middle Aged , Predictive Value of Tests , Aged , AdolescentABSTRACT
BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454â419â days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), Pâ=â0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, Pâ<â0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, Pâ=â0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all Pâ<â0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.
Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Interrupted Time Series Analysis , Humans , Longitudinal Studies , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Female , Male , Middle Aged , Adult , Aged , Bacteremia/drug therapy , Bacteremia/microbiology , Drug Resistance, Bacterial , Leukemia/drug therapy , Leukemia/complications , Drug Utilization/statistics & numerical data , Drug Utilization/standardsABSTRACT
BACKGROUND: The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia. METHODS: This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained. RESULTS: The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2. CONCLUSION: While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/blood , COVID-19/epidemiology , COVID-19/complications , Male , Female , Retrospective Studies , Adult , Middle Aged , Saudi Arabia/epidemiology , Young Adult , Leukemia/blood , Leukemia/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Aged , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/complications , Adolescent , ComorbidityABSTRACT
BACKGROUND: Among leukemia patients, sleep disruptions are prevalent and can profoundly affect their overall quality of life. Acupressure and foot reflexology, modalities rooted in traditional Chinese medicine, have garnered attention for their potential to address sleep disturbances and mitigate associated symptoms. METHODS: This research utilized a randomized controlled trial with a pretest-posttest design involving 102 leukemia patients admitted to Imam Khomeini Hospital in Urmia. Participants were randomly allocated to 3 groups: acupressure (n = 34), reflexology (n = 34), or control (n = 34). Prior to the intervention, patients completed a demographic survey and the Pittsburgh Sleep Quality Index (PSQI) for baseline assessments. Acupressure involved stimulation of the SP6 point twice daily for 10 minutes over 4 weeks, while reflexology entailed daily 10-minute sessions with sweet almond oil on the soles for the same duration. The control group received standard care without additional interventions. Following the 4-week intervention period, post-intervention evaluations were conducted using identical measurement tools. RESULTS: The findings underscored the efficacy of both acupressure and foot reflexology in significantly improving sleep quality within the intervention groups (P < .001). Initially, there were no notable differences in sleep quality among the 3 groups (P > .05). Subsequently, pairwise comparisons adjusted with Bonferroni corrections revealed significant disparities in sleep quality between the acupressure and reflexology groups compared to the control group (P < .001). However, post-intervention analysis indicated no statistically significant variance in enhancing sleep quality between the acupressure and foot reflexology groups (P < .05). CONCLUSION: This study demonstrates that acupressure and foot reflexology interventions can enhance sleep quality in individuals with leukemia. These findings support the effectiveness of these complementary modalities, offering targeted relief and relaxation. While these non-invasive therapies show promise in improving well-being, further research is needed to confirm and expand upon these results due to study limitations.
Subject(s)
Acupressure , Foot , Leukemia , Quality of Life , Sleep Quality , Humans , Acupressure/methods , Male , Female , Middle Aged , Adult , Foot/physiopathology , Leukemia/complications , Leukemia/therapy , Massage/methods , Sleep Wake Disorders/therapy , Medicine, Chinese Traditional/methods , Treatment OutcomeABSTRACT
OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.
Subject(s)
Leukemia, Myeloid, Acute , Mucormycosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Mucormycosis/diagnosis , Male , Female , Adult , Middle Aged , Prognosis , Retrospective Studies , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antifungal Agents/therapeutic use , Young Adult , Leukemia/complications , Leukemia/drug therapyABSTRACT
BACKGROUND: The incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied. METHODS: Systematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis. RESULTS: Effect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children. CONCLUSIONS: Both underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.
Subject(s)
Body Mass Index , Humans , Child , Leukemia/diagnosis , Leukemia/mortality , Leukemia/complications , Thinness/complications , Obesity/complications , Child, PreschoolABSTRACT
Klebsiella pneumoniae is an opportunistic pathogen that can colonize the gastrointestinal tract (GIT) of humans. The mechanisms underlying the successful translocation of this pathogen to cause extra-intestinal infections remain unknown, although virulence and antimicrobial resistance traits likely play significant roles in the establishment of infections. We investigated K. pneumoniae strains isolated from GIT colonization (strains Kp_FZcol-1, Kp_FZcol-2 and Kp_FZcro-1) and from a fatal bloodstream infection (strain Kp_HM-1) in a leukemia patient. All strains belonged to ST307, carried a transferable IncF plasmid containing the blaCTX-M-15 gene (pKPN3-307 TypeA-like plasmid) and showed a multidrug-resistance phenotype. Phylogenetic analysis demonstrated that Kp_HM-1 was more closely related to Kp_FZcro-1 than to the other colonizing strains. The Kp_FZcol-2 genome showed 81 % coverage with the Kp_HM-1 246,730 bp plasmid (pKp_HM-1), lacking most of its putative virulence genes. Searching public genomes with similar coverage, we observed the occurrence of this deletion in K. pneumoniae ST307 strains recovered from human colonization and infection in different countries. Our findings suggest that strains lacking the putative virulence genes found in the pKPN3-307 TypeA plasmid are still able to colonize and infect humans, highlighting the need to further investigate the role of these genes for the adaptation of K. pneumoniae ST307 in distinct human body sites.
Subject(s)
Gastrointestinal Tract , Klebsiella Infections , Klebsiella pneumoniae , Leukemia , Phylogeny , beta-Lactamases , Humans , Male , Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , beta-Lactamases/genetics , beta-Lactamases/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Gastrointestinal Tract/microbiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/pathogenicity , Klebsiella pneumoniae/drug effects , Leukemia/microbiology , Leukemia/complications , Microbial Sensitivity Tests , Plasmids/genetics , Virulence/genetics , Virulence Factors/genetics , Middle AgedABSTRACT
OBJECTIVE: To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed. RESULTS: Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%). CONCLUSION: Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.
Subject(s)
Hematologic Neoplasms , Humans , Hematologic Neoplasms/complications , Hearing Loss/etiology , Lymphoma/complications , Multiple Myeloma/complications , Ear Diseases/etiology , Facial Paralysis/etiology , Leukemia/complicationsABSTRACT
PURPOSE: Leukemias have been associated with oral manifestations, reflecting susceptibility to cancer therapy-induced oral mucositis. We sought to identify SNPs associated with both leukemia and oral mucositis (OM). METHODS: Whole exome sequencing was performed on leukemia and non-cancer blood disorder (ncBD) patients' saliva samples (N = 50) prior to conditioning therapy. WHO OM grading scores were determined: moderate to severe (OM2-4) vs. none to mild (OM0-1). Reads were processed using Trim Galorev0.6.7, Bowtie2v2.4.1, Samtoolsv1.10, Genome Analysis Toolkit (GATK)v4.2.6.1, and DeepVariantv1.4.0. We utilized the following pipelines: P1 analysis with PLINK2v3.7, SNP2GENEv1.4.1 and MAGMAv1.07b, and P2 [leukemia (N = 42) vs. ncBDs (N = 8)] and P3 [leukemia + OM2-4 (N = 18) vs. leukemia + OM0-1 (N = 24)] with Z-tests of genotypes and protein-protein interaction determination. GeneCardsSuitev5.14 was used to identify phenotypes (P1 and P2, leukemia; P3, oral mucositis) and average disease-causing likelihood and DGIdb for drug interactions. P1 and P2 genes were analyzed with CytoScape plugin BiNGOv3.0.3 to retrieve overrepresented Gene Ontology (GO) terms and Ensembl's VEP for SNP outcomes. RESULTS: In P1, 457 candidate SNPs (28 genes) were identified and 21,604 SNPs (1016 genes) by MAGMAv1.07b. Eighteen genes were associated with "leukemia" per VarElectv5.14 analysis and predicted to be deleterious. In P2 and P3, 353 and 174 SNPs were significant, respectively. STRINGv12.0 returned 77 and 32 genes (C.L. = 0.7) for P2 and P3, respectively. VarElectv5.14 determined 60 genes from P2 associated with "leukemia" and 11 with "oral mucositis" from P3. Overrepresented GO terms included "cellular process," "signaling," "hemopoiesis," and "regulation of immune response." CONCLUSIONS: We identified candidate SNPs possibly conferring susceptibility to develop leukemia and oral mucositis.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia , Mucositis , Stomatitis , Humans , Polymorphism, Single Nucleotide , Pilot Projects , Hematopoietic Stem Cell Transplantation/adverse effects , Stomatitis/genetics , Stomatitis/chemically induced , Leukemia/genetics , Leukemia/therapy , Leukemia/complications , Behavior TherapyABSTRACT
Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.
Subject(s)
Antiviral Agents , Cytomegalovirus Infections , Cytomegalovirus , Foscarnet , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Valganciclovir , Viremia , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Cytomegalovirus Infections/etiology , Valganciclovir/therapeutic use , Male , Female , Viremia/drug therapy , Adult , Antiviral Agents/therapeutic use , Foscarnet/therapeutic use , Middle Aged , Cytomegalovirus/drug effects , Retrospective Studies , Young Adult , Aged , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/mortality , Treatment Outcome , Leukemia/therapy , Leukemia/complications , Leukemia/mortalityABSTRACT
Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.
Subject(s)
Clostridium Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia , Adult , Humans , Vancomycin/therapeutic use , Metronidazole/therapeutic use , Retrospective Studies , Poland , Prospective Studies , Graft vs Host Disease/etiology , Leukemia/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Clostridium Infections/drug therapy , Clostridium Infections/etiologyABSTRACT
Introducción: La tasa de mortalidad de la candidemia es variable, pero puede estar influenciada por la patología de base, en especial aquella que condiciona la presencia de neutropenia. En niños con patología oncohematológica, son pocos los trabajos que han abordado la mortalidad relacionada a candidemias y sus factores asociados. Las preguntas que promueven esta revisión sistemática, son: ¿Cuáles son las características epidemiológicas, clínicas y de evolución de los pacientes pediátricos oncohematológicos con candidemia? ¿Cuál es la mortalidad relacionada con esta entidad? Materiales y métodos: Revisión sistemática de la literatura. Se utilizaron los siguientes términos de búsqueda: candidemia por Candida spp. y los siguientes filtros humanos, niños y adolescentes y patología oncohematológica. Se revisaron los artículos publicados en inglés, español o francés hasta el 21 de septiembre de 2023. Las referencias bibliográficas de los artículos incluidos se revisaron manualmente para identificar estudios relevantes adicionales. Resultados: Se encontraron 66 artículos. Del análisis cualitativo realizado en sus textos completos, quedaron finalmente 4 estudios que se consideró que cumplían con los criterios de inclusión. Todos los artículos seleccionados sumaron 191 pacientes con diversas patologías oncohematológicas. La presencia de accesos vasculares fue frecuente en esta serie y la no extracción del catéter venoso central fue el factor más prevalente entre los que fallecieron. El agente infectante predominante fue Candida no albicans y la mortalidad osciló entre el 11,3 y el 31% con una mediana de 25%. No fue posible establecer si la especie de Candida influía en la letalidad
Introduction: The mortality rate of candidemia is variable, but may be influenced by underlying diseases, especially those causing neutropenia. In children with cancer and blood disorders, few studies have addressed mortality related to candidemia and its associated factors. The questions that motivated this systematic review were: What are the epidemiological, clinical and outcome characteristics of pediatric cancer patients with candidemia? What is the mortality related to this condition? Materials and methods: Systematic review of the literature. The following search terms were used: Candida spp., candidemia, with the following filters: human, children and adolescents, and cancer and blood disorders. Articles published in English, Spanish, or French up to September 21, 2023 were reviewed. References of included articles were manually reviewed to identify additional relevant studies. Results: 66 articles were identified. From the qualitative analysis carried out on their full texts, 4 studies that were considered to meet the inclusion criteria were finally selected. The selected articles included a total of 191 patients with various types of cancer and blood disorders. The presence of vascular access was common in this series and failure to remove the central venous catheter was the most prevalent factor among those who died. The predominant infectious agent was non-albicans Candida and mortality ranged from 11.3% to 31% with a median of 25%. It was not possible to establish whether Candida species influenced mortality.
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Leukemia/complications , Risk Factors , Hospital Mortality , Candidemia/microbiology , Candidemia/mortality , Neoplasms/complications , Immunocompromised Host , Antifungal Agents/therapeutic useSubject(s)
Interleukin 1 Receptor Antagonist Protein , Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/complications , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin 1 Receptor Antagonist Protein/adverse effects , Male , Female , Treatment Outcome , Middle Aged , Adult , Aged , Leukemia/drug therapy , Leukemia/complicationsABSTRACT
PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.