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EJHaem Feb 2024Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone...
Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy.
PubMed: 38406549
DOI: 10.1002/jha2.841 -
BMC Health Services Research Sep 2017We sought to examine the relationship between child specific health aid (CHA) and burden of disease. Based on existing evidence, we hypothesized that foreign aid for...
BACKGROUND
We sought to examine the relationship between child specific health aid (CHA) and burden of disease. Based on existing evidence, we hypothesized that foreign aid for child health would not be proportional to burden of disease.
METHODS
In order to examine CHA and burden of disease, we obtained estimates of these parameters from established sources. Estimates of disability adjusted life years (DALYs) in children (0-5 years) were obtained from the World Health Organization for 2000 and 2012. The 10 most burdensome disease categories in each continent, excluding high-income countries, were identified for study. Descriptions of all foreign aid commitments between 1996 and 2009 were obtained from AidData, and an algorithm to designate the target diseases of the commitments was constructed. Data were examined in scatterplots for trends.
RESULTS
The most burdensome childhood diseases varied by continent. In all continents, newborn diseases, vaccine-preventable diseases (lower respiratory diseases, measles, meningitis, tetanus, and pertussis), and diarrheal diseases ranked within the four most burdensome diseases. Infectious diseases such as malaria, tuberculosis, and HIV were also among the ten most burdensome diseases in sub-Saharan Africa, and non-communicable diseases were associated with much of the burden in the other continents. CHA grew from $7.4 billion in 1996 to $17.7 billion in 2009 for our study diseases. Diarrheal diseases and malnutrition received the most CHA as well as the most CHA per DALY. CHA directed at HIV increased dramatically over our study period, from $227,000 in 1996 to $3.4 billion in 2008. Little aid was directed at injuries such as drowning, car accidents, and fires, as well as complex medical diseases such as leukemia and endocrine disorders.
CONCLUSION
CHA has grown significantly over the last two decades. There is no clear relationship between CHA and burden of disease. This report provides a description of foreign aid for child health, and hopes to inform policy and decision-making regarding foreign aid.
Topics: Africa South of the Sahara; Child; Child Health; Child, Preschool; Communicable Diseases; Cost of Illness; Cross-Sectional Studies; Disabled Persons; Female; Global Health; Humans; Income; Infant; Infant, Newborn; International Cooperation; Male; Noncommunicable Diseases; Quality-Adjusted Life Years
PubMed: 28915813
DOI: 10.1186/s12913-017-2540-5 -
British Journal of Cancer Apr 2024Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest...
BACKGROUND
Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort.
METHODS
Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated.
RESULTS
In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50.
DISCUSSION
Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.
Topics: Humans; Adolescent; Adult; Middle Aged; Meningioma; Risk Factors; Neoplasms, Second Primary; Central Nervous System Neoplasms; Glioma; Survivors; Leukemia; Europe; Meningeal Neoplasms; Incidence
PubMed: 38243010
DOI: 10.1038/s41416-024-02577-y -
The Permanente Journal Jun 2022Introduction Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Extramedullary involvement in the central nervous system (CNS) is...
Introduction Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Extramedullary involvement in the central nervous system (CNS) is a rare complication of the disease, and less than 200 cases have been reported. We report a case of leptomeningeal involvement of CLL that presented as an acute encephalopathy. Case presentation A 76-year-old man with treatment-naïve, Rai stage 0 CLL presented with altered mental status. Cerebrospinal-fluid studies, including flow cytometry, confirmed the leptomeningeal involvement of the previously diagnosed CLL. Surveillance imaging and lab studies showed no evidence of disease progression or Richter's transformation. One-time intrathecal methotrexate resulted in transient improvement of his mental status. Conclusion CLL patients with new-onset neurologic manifestations should be evaluated for the CNS involvement of the neoplasm via brain imaging and cerebrospinal-fluid flow cytometry. This CNS involvement of CLL is associated with poor clinical outcomes. Intrathecal treatment with methotrexate, cytarabine, and steroid may improve neurologic symptoms.
Topics: Adult; Aged; Brain Diseases; Disease Progression; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Meninges; Methotrexate
PubMed: 35933656
DOI: 10.7812/TPP/21.081 -
Hematology Reports Aug 2022The congenital immune system includes neutrophils, which perform a variety of functions. Congenital and acquired neutropenia are rare illnesses with an underestimated...
The congenital immune system includes neutrophils, which perform a variety of functions. Congenital and acquired neutropenia are rare illnesses with an underestimated prevalence in children. The aim of this study is to examine the epidemiology and etiology of febrile neutropenia in children at Haiphong Children's Hospital, Haiphong, Vietnam. A cross-sectional study was carried out on 421 febrile neutropenia children. Clinical and laboratory characteristics were examined. The median age (IQR) was 25.0 (12.5-59.5) months. The male-to-female ratio was 1.35/1. There were twice as many children living in the suburbs (66.98%) as in urban areas (33.02%). The mean (SD) temperature at admission was 38.50 ± 0.59 °C. Diagnosed causes associated with neutropenia included acute respiratory infections 250 (59.45%), gastrointestinal infections 68 (16.1%), erythema 37 (8.79%), acute leukemia 15 (3.56%), urinary tract infection 5 (1.19%), and encephalitis/meningitis 4 (0.95%). Viral etiology accounted for 61.52% (259): -50.19% (130), -31.27% (81), -14.67% (38), 1-93% (5), rotavirus-1.54% (4), and -0.4% (1). Twenty-five patients (5.94%) were found to have bacteria in their cultures, with being the most common (eight patients; 32%). Febrile neutropenia was common in children under 2 years old. Primary clinical manifestations were acute upper respiratory tract infections, and viruses most commonly caused febrile neutropenia. Further studies with larger sample sizes are needed to determine the cause of febrile neutropenia.
PubMed: 35997401
DOI: 10.3390/hematolrep14030034 -
Case Reports in Oncology 2022Chronic lymphocytic leukemia (CLL) involves the proliferation of a clonal population of B cells within the bone marrow that classically spreads to the blood and...
Chronic lymphocytic leukemia (CLL) involves the proliferation of a clonal population of B cells within the bone marrow that classically spreads to the blood and lymphatic system. Central nervous system (CNS) manifestations of CLL occur rarely, and no gold standard treatment regimen has been designated to date. We report a case of CLL with CNS involvement in a 68-year-old woman who presented with a severe headache 4 years after initial diagnosis. She was started on ibrutinib, which failed to clear her CSF of malignancy. Venetoclax was then added, and this was successful in clearing her CSF. For its CNS penetration and efficacy in achieving CSF remission of CLL, we propose that venetoclax be considered as a treatment option for CLL meningitis.
PubMed: 35529288
DOI: 10.1159/000523858 -
Frontiers in Immunology 2021Leptomeningeal disease (LMD) in melanoma patients is associated with significant neurological sequela and has a dismal outcome, with survival measured typically in...
Leptomeningeal disease (LMD) in melanoma patients is associated with significant neurological sequela and has a dismal outcome, with survival measured typically in weeks. Despite the therapeutic benefit of targeted therapies and immunotherapies for Stage IV melanoma, patients with LMD do not typically benefit. A deeper understanding of the tumor microenvironment (TME) of LMD may provide more appropriate therapeutic selection. A retrospective analysis of subjects who underwent surgical resection with LMD (n=8) were profiled with seven color multiplex staining to evaluate the expression of the global immune suppressive hub - the signal transducer and activator of transcription 3 (STAT3) and for the presence of CD3+ T cells, CD68+ monocyte-derived cells, CD163+ immune suppressive macrophages, and CD11c+ cells [potential dendritic cells (DCs)] in association with the melanoma tumor marker S100B and DAPI for cellular nuclear identification. High-resolution cellular imaging and quantification was conducted using the Akoya Vectra Polaris. CD11c+ cells predominate in the TME (10% of total cells), along with immunosuppressive macrophages (2%). Another potential subset of DCs co-expressing CD11c+ and the CD163+ immunosuppressive marker is frequently present (8/8 of specimens, 8%). Occasional CD3+ T cells are identified, especially in the stroma of the tumor (p=0.039). pSTAT3 nuclear expression is heterogeneous in the various immune cell populations. Occasional immune cluster interactions can be seen in the stroma and on the edge. In conclusion, the TME of LMD is largely devoid of CD3+ T cells but is enriched in immune suppression and innate immunity.
Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD11c Antigen; Dendritic Cells; Female; Humans; Lymphocytes, Tumor-Infiltrating; Macrophages; Male; Melanoma; Meningeal Neoplasms; Middle Aged; Neoplasm Proteins; Receptors, Cell Surface; Retrospective Studies; STAT3 Transcription Factor; T-Lymphocyte Subsets; Tumor Microenvironment
PubMed: 34691054
DOI: 10.3389/fimmu.2021.745893 -
Pathology Oncology Research : POR 2022Central nervous system (CNS) involvement is a leading cause of therapy-refractory pediatric acute lymphoblastic leukemia (pALL), which is aggravated by underdiagnosing...
Central nervous system (CNS) involvement is a leading cause of therapy-refractory pediatric acute lymphoblastic leukemia (pALL), which is aggravated by underdiagnosing CNS disease with the currently used cell-based approach of cerebrospinal fluid (CSF) diagnostics. Our study focused on developing novel subcellular CNS leukemia indicators in the CSF and the bone marrow (BM) of patients with pALL. Serial liquid biopsy samples ( = 65) were analyzed by Elisas to measure the level of essential proteins associated with blast cell CNS trafficking, vascular endothelial growth factor A (VEGF-A) and integrin alpha 6 (ITGA6). In CSF samples from early induction chemotherapy, VEGF-A concentration were uniformly elevated in the CNS-positive group compared to those patients without unambiguous meningeal infiltration (9 vs Nine patients, Δc = 17.2 pg/ml, = 0.016). Expression of miR-181a, a -regulating microRNA which showed increased level in CNS leukemia in our previous experiments, was then paralleled with VEGF-A concentration. A slight correlation between the levels of miR-181a and VEGF-A indicators in CSF and BM samples was revealed ( = 46, Pearson's = 0.36, = 0.015). After validating in international cohorts, the joint quantification of miR-181a and VEGF-A might provide a novel tool to precisely diagnose CNS involvement and adjust CNS-directed therapy in pALL.
Topics: Central Nervous System; Central Nervous System Neoplasms; Child; Humans; MicroRNAs; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Vascular Endothelial Growth Factor A
PubMed: 35449729
DOI: 10.3389/pore.2022.1610096 -
PeerJ 2017remains the leading causative pathogen in pediatric pneumonia and bacteremia throughout the world. The invasive pneumococcal disease (IPD) is known as isolation of...
remains the leading causative pathogen in pediatric pneumonia and bacteremia throughout the world. The invasive pneumococcal disease (IPD) is known as isolation of from a normally sterile site (e.g., blood, cerebrospinal fluid, synovial fluid, pericardial fluid, pleural fluid, or peritoneal fluid). The aim of this study is to survey the clinical manifestations and laboratory results of IPD and identify the prognostic factors of mortality. From January 2001 to December 2006, a retrospective review of chart was performed in a teaching hospital in Taipei. The hospitalized pediatric patients with the diagnosis of pneumonia, arthritis, infectious endocarditis, meningitis or sepsis were recruited. Among them, 50 patients were pneumococcal infections proved by positive culture results or antigen tests. Clinical manifestations, laboratory data and hospitalization courses were analyzed. The median age was 3.5-year-old and there were 30 male patients (60%). Eight patients (16%) had underlying disease such as leukemia or congenital heart disease. Hemolytic uremic syndrome (HUS) was observed in ten patients and extracorporeal membrane oxygenation (ECMO) was performed in three patients. Leukocytosis, elevated C-reactive protein and AST level were noted in most of the patients. The overall mortality rate was 10%. We found that leukopenia, thrombocytopenia and high CRP level were significant predictors for mortality. In conclusion, remains an important health threat worldwide and IPD is life-threatening with high mortality rate. We found leukopenia, thrombocytopenia, and high CRP levels to be associated with mortality in pediatric IPD, and these factors are worthy of special attention at admission. Although we failed to identify a statistically significant prognostic factor in multivariate analysis due to relatively small sample size, we suggest an aggressive antibiotic treatment in patients with these factors at admission. Further large-scale studies are warranted.
PubMed: 28149700
DOI: 10.7717/peerj.2941 -
International Journal of Infectious... May 2021To determine the risk of invasive pneumococcal disease (IPD) in adult cancer patients stratified by type of underlying malignancy, age, and capsular serotype and to...
OBJECTIVES
To determine the risk of invasive pneumococcal disease (IPD) in adult cancer patients stratified by type of underlying malignancy, age, and capsular serotype and to assess herd effects of childhood pneumococcal vaccination.
METHODS
All adult IPD cases reported to the Dutch pneumococcal surveillance system between 2004 and 2016 were included in this study. IPD incidence rates (IR) stratified by subtype of malignancy were calculated per 100 000 patient-years of follow-up. Incidence rate ratios (IRR) were calculated to compare IRs between groups.
RESULTS
A total of 7167 IPD cases were included, of which 1453 were in patients with malignancies. For patients with hematological malignancies (HM) and solid organ malignancies (SOM), IRs were 482/100 000 and 79/100 000, respectively, compared with 15/100 000 in controls. The highest incidence was observed among patients with multiple myeloma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, pancreatic cancer, and lung cancer (3299/100 000, 2717/100 000, 538/100 000, 559/100 000, and 393/100 000, respectively), and in patients ≥50 years old. Among HM patients, the incidence of IPD declined significantly after the implementation of infant pneumococcal vaccination (IRR 0.65, 95% confidence interval 0.51-0.84); among SOM patients, the decline was not statistically significant (IRR 0.88, 95% confidence interval 0.72-1.07).
CONCLUSIONS
The IPD disease burden in cancer patients remains high. Large differences in IPD incidence between the different types of cancer demand tailored guidance regarding pneumococcal vaccination.
Topics: Adolescent; Adult; Cohort Studies; Ethnicity; Hematologic Neoplasms; Humans; Incidence; Male; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup
PubMed: 33781907
DOI: 10.1016/j.ijid.2021.03.072