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Cancer Jun 2023Hyperleukocytosis in patients with acute myeloid leukemia (AML) has been associated with worse outcomes. For cytoreduction, leukapheresis has been used but its clinical...
BACKGROUND
Hyperleukocytosis in patients with acute myeloid leukemia (AML) has been associated with worse outcomes. For cytoreduction, leukapheresis has been used but its clinical utility is unknown, and low-dose cytarabine (LD-cytarabine) is used as an alternative method.
METHODS
Children with newly diagnosed AML treated between 1997 and 2017 in institutional protocols were studied. Hyperleukocytosis was defined as a leukocyte count of ≥100 × 10 /L at diagnosis. Clinical characteristics, early complications, survival data, and effects of cytoreductive methods were reviewed. Among 324 children with newly diagnosed AML, 49 (15.1%) presented with hyperleukocytosis. Initial management of hyperleukocytosis included leukapheresis or exchange transfusion (n = 16, considered as one group), LD-cytarabine (n = 18), hydroxyurea (n = 1), and no leukoreduction (n = 14).
RESULTS
Compared with patients who received leukapheresis, the percentage decrease in leukocyte counts following intervention was greater among those who received LD-cytarabine (48% vs. 75%; p = .02), with longer median time from diagnosis to initiation of protocol therapy (28.1 vs. 95.2 hours; p < .001). The incidence of infection was higher in patients (38%) who had leukapheresis than those who receive LD-cytarabine (0%) or leukoreduction with protocol therapy (14%) (p = .008). No differences were noted in the outcomes among the intervention groups. Although patients with hyperleukocytosis had higher incidences of pulmonary and metabolic complications than did those without, no early deaths occurred, and the complete remission, event-free survival, overall survival rates, and outcomes of both groups were similar.
CONCLUSION
LD-cytarabine treatment appears to be a safe and effective means of cytoreduction for children with AML and hyperleukocytosis.
Topics: Humans; Child; Cytoreduction Surgical Procedures; Leukocytosis; Leukemia, Myeloid, Acute; Leukocyte Count; Leukapheresis; Cytarabine
PubMed: 36943896
DOI: 10.1002/cncr.34751 -
Ticks and Tick-borne Diseases Sep 2022CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved...
CXCL13 in cerebrospinal fluid has gradually become an established biomarker for Lyme neuroborreliosis (LNB), however the diagnostic performance of CXCL13 may be improved by the addition of IL-6, a non-specific infection biomarker. The aim of this study was to measure the concentrations of CXCL13 and IL-6 in cerebrospinal fluid, in the attempt to evaluate the diagnostic performance of these two biomarkers, in the differentiation between definite and possible LNB, as well as between LNB and other neuroinfections. This study used a cross-sectional design to quantify the levels of CXCL13 and IL-6 in cerebrospinal fluid (CSF) specimens from consecutive patients examined for central nervous system (CNS) infections at Lillebaelt Hospital in the Region of Southern Denmark. CXCL13 and IL-6 were measured simultaneously using the Bio-Plex 200 multiplex Cytokine Immunoassay System (Bio-Rad). Based on clinical and paraclinical findings, we grouped patients into six separate groups: definite LNB, possible LNB, Viral CNS infection, non-Borrelia Bacterial CNS infection, Other CNS disease (with pleocytosis) and Negative (without pleocytosis). A combined interpretation of four variables (leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF) is presented using principal component cluster analysis. We included by chart review 390 patients discharged with definite LNB (n = 31), possible LNB (n = 10), confirmed Viral or non-Borrelia Bacterial CNS infection (n = 34), Other CNS disease (n = 58), and Negative (n = 257) for CXCL13 and IL-6 analysis. Principal component analysis (PCA) revealed three distinct clusters based on leukocyte cell counts, protein concentration, CXCL13 and IL-6 concentrations in CSF from 380 included patients (10 possible LNB patients excluded). The clusters clearly differentiate the groups: definite LNB, non-Borrelia Bacterial CNS infection and Negative (without pleocytosis). A receiver operating characteristic (ROC) curve comparing LNB patients (n = 31) and all non-LNB conditions with CSF pleocytosis (n = 99) indicated an optimal CXCL13 cut-off value of 50.7 pg/mL, resulting in a sensitivity and a specificity of 93.6 and 91.1%, respectively. The ROC analysis comparing patients with confirmed non-LNB CNS infection (n = 34) and all others with CSF pleocytosis (n = 97) resulted in an optimal IL-6 cut-off value of 111.5 pg/mL, yielding a sensitivity and a specificity of 78.8% and 82.5% respectively. Of the ten possible LNB patients, three cases (with CXCL13 levels above cut-off) fall within the LNB cluster, and one case is just outside, providing some laboratory support for the diagnosis of LNB. The remaining six possible LNB patients (with CXCL13 levels below the 50.7 cut-off) had little support for the diagnosis of LNB in the PCA-plot. The results of this study confirm that CXCL13 is a valuable supplement for diagnosis of LNB, and that the combination of CXCL13 and IL-6 may be used to differentiate cases of LNB from other CNS infections. Furthermore, IL-6 can be of differential diagnostic value when evaluating patients with possible LNB.
Topics: Biomarkers; Central Nervous System Infections; Chemokine CXCL13; Cross-Sectional Studies; Humans; Interleukin-6; Leukocytosis; Lyme Neuroborreliosis
PubMed: 35709639
DOI: 10.1016/j.ttbdis.2022.101984 -
Haematologica May 2018
Topics: B-Lymphocytes; Genomics; Hematopoiesis; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytosis; Mutation
PubMed: 29712819
DOI: 10.3324/haematol.2018.191098 -
Medicine Jun 2021Aseptic meningoencephalitis is a rare central nervous system complication of relapsing polychondritis (RP).
RATIONALE
Aseptic meningoencephalitis is a rare central nervous system complication of relapsing polychondritis (RP).
PATIENT
We report a 61-year-old Japanese male patient with spiking fever and impaired consciousness. Neurological examination revealed meningealirritation, and cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis with elevated protein (199 mg/dL) and interleukin-6 (3810 pg/mL). Serological analysis showed high levels of anti-type II collagen antibodies, and the result of auricular biopsy was consistent with the diagnosis of RP showing cartilage degeneration surrounded by inflammatory cell infiltrations.
DIAGNOSIS
A clinical diagnosis of RP was made according to the diagnostic criteria established by MacAdams et al.
INTERVENTION
Steroid pulse therapy (methylprednisolone 1000 mg, consecutive 3 days) followed by oral prednisolone (60 mg/day) resolved the patient's high fever and disturbance of consciousness.
OUTCOMES
The patient rapidly improved after steroid treatments and has a normal quality of life under the maintenance dose of steroid plus methotrexate (4 mg/week).
LESSONS
RP-associated meningoencephalitis is a rare complication with significant morbidity and mortality. It should be considered and differentiated in patients with RP with unexplained spiking fever and impaired consciousness. In addition, the assessment of cerebrospinal fluid interleukin-6 levels may be useful to investigate the disease activity of RP-related meningoencephalitis. Further prospective studies are required to confirm this result.
Topics: Glucocorticoids; Humans; Interleukin-6; Leukocytosis; Male; Meningoencephalitis; Methylprednisolone; Middle Aged; Polychondritis, Relapsing
PubMed: 34128872
DOI: 10.1097/MD.0000000000026315 -
Laboratory Investigation; a Journal of... Apr 2023Environmental enteric dysfunction (EED) is characterized by malabsorption and diarrhea that result in irreversible deficits in physical and intellectual growth. We...
Environmental enteric dysfunction (EED) is characterized by malabsorption and diarrhea that result in irreversible deficits in physical and intellectual growth. We sought to define the expression of transport and tight junction proteins by quantitative analysis of duodenal biopsies from patients with EED. Biopsies from Pakistani children with confirmed EED diagnoses were compared to those from age-matched North American healthy controls, patients with celiac disease, and patients with nonceliac disease with villous atrophy or intraepithelial lymphocytosis. Expression of brush border digestive and transport proteins and paracellular (tight junction) proteins was assessed by quantitative multiplex immunofluorescence microscopy. EED was characterized by partial villous atrophy and marked intraepithelial lymphocytosis. Epithelial proliferation and enteroendocrine, tuft, and Paneth cell numbers were unchanged, but there was significant goblet cell expansion in EED biopsies. Expression of proteins involved in nutrient and water absorption and that of the basolateral Cl transport protein NKCC1 were also increased in EED. Finally, the barrier-forming tight junction protein claudin-4 (CLDN4) was significantly upregulated in EED, particularly within villous enterocytes. In contrast, expression of CFTR, CLDN2, CLDN15, JAM-A, occludin, ZO-1, and E-cadherin was unchanged. Upregulation of a barrier-forming tight junction protein and brush border and basolateral membrane proteins that support nutrient and water transport in EED is paradoxical, as their increased expression would be expected to be correlated with increased intestinal barrier function and enhanced absorption, respectively. These data suggest that EED activates adaptive intestinal epithelial responses to enhance nutrient absorption but that these changes are insufficient to restore health.
Topics: Child; Humans; Intestinal Mucosa; Lymphocytosis; Tight Junctions; Tight Junction Proteins; Atrophy
PubMed: 36870290
DOI: 10.1016/j.labinv.2022.100036 -
Pediatrics and Neonatology May 2021Enteroviral meningitis is typically diagnosed as the presence of pleocytosis and of viral RNA in cerebrospinal fluid. However, it was recently reported that more than...
BACKGROUND
Enteroviral meningitis is typically diagnosed as the presence of pleocytosis and of viral RNA in cerebrospinal fluid. However, it was recently reported that more than 50% of infants with enteroviral meningitis diagnosed by polymerase chain reaction had no cerebrospinal fluid pleocytosis. This study investigated type I interferon (IFN) and cytokine profiles in the cerebrospinal fluid based on the presence or absence of cerebrospinal fluid pleocytosis in children with enteroviral meningitis.
METHODS
We included 51 enteroviral meningitis patients showing cerebrospinal fluid pleocytosis (pleocytosis group), 31 enteroviral meningitis patients without cerebrospinal fluid pleocytosis (non-pleocytosis group), and 52 controls (control group) and compared cerebrospinal fluid interleukin 6 (IL-6), IL-8, chemokine (C-X-C motif) ligand 10 (CXCL-10), IFN-α, and IFN-β levels.
RESULTS
A significant difference was observed in IL-6, IL-8, and CXCL-10 levels across the three groups, with highest values in the pleocytosis patients, followed by those in the non-pleocytosis and control subjects. IFN-α level was higher in the pleocytosis group than in the non-pleocytosis and control groups. Meanwhile, the IFN-β level was higher in the pleocytosis and non-pleocytosis groups than in the control group (34.54 [31.23-38.59] pg/mL vs. 33.21 [31.23-35.21] pg/mL vs. 0.00 [0.00-0.00] pg/mL, respectively; P < 0.001). Furthermore, cerebrospinal fluid IFN-β was detected in all patients with enteroviral meningitis, except one (98.8%) regardless of pleocytosis, whereas it was detected in only two (3.8%) control subjects (P < 0.001).
CONCLUSION
The cerebrospinal fluid cytokine profiles remarkably differed based on the presence or absence of cerebrospinal fluid pleocytosis. Further investigations are required to determine whether cerebrospinal fluid IFN-β could be used as a surrogate marker of viral meningitis instead of cerebrospinal fluid pleocytosis.
Topics: Child; Cytokines; Enterovirus Infections; Humans; Infant; Interferon Type I; Leukocytosis; Meningitis, Viral; Polymerase Chain Reaction
PubMed: 33707153
DOI: 10.1016/j.pedneo.2021.02.002 -
AIDS (London, England) Mar 2024HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it...
OBJECTIVE
HIV-1 invades the brain within days post-transmission. This study quantitated cerebrospinal fluid (CSF) white blood cell count (WBC) and investigated whether it associated with plasma and CSF HIV-1 RNA during untreated acute HIV infection (AHI).
DESIGN
Seventy participants underwent lumbar puncture during Fiebig stages I-V AHI.
METHOD
WBC and HIV-1 RNA with a lower limit of quantification (LLQ) of 80 copies/ml were measured in CSF.
RESULTS
Sixty-nine (99%) participants were men, with a median age of 26. Their blood CD4 + and CD8 + T-cell counts were 335 [interquartile range (IQR) 247-553) and 540 (IQR 357-802) cells/μl, respectively. Forty-five (64%) were in Fiebig stages III-V whereas 25 (36%) were in Feibig stages I-II. Fifty-two (74%) experienced acute retroviral syndrome. Median plasma and CSF HIV-1 RNA were 6.10 (IQR 5.15-6.78) and 3.15 (IQR 1.90-4.11) log 10 copies/ml, respectively. Sixteen (23%) CSF samples had HIV-1 RNA below LLQ. Median CSF WBC was 2.5 (IQR 1-8) cells/μl. CSF pleocytosis (WBC >5) was observed in 33% and was only present in CSF samples with detectable HIV-1 RNA. The frequencies of CSF pleocytosis during Fiebig stages III-V and among CSF samples of higher viral load (>1000 copies/ml) were 42 and 45%, respectively. Pleocytosis independently associated with CSF HIV-1 RNA in multivariate analysis [adjusted coefficient: 0.79, 95% confidence interval (CI) 0.41-1.14), P < 0.001] and a lower plasma to CSF HIV-1 RNA ratio ( P < 0.001).
CONCLUSION
CSF pleocytosis was present in one-third of participants with AHI. It associated with higher CSF HIV-1 RNA and a lower plasma to CSF HIV-1 RNA ratio, suggesting a potential association with HIV-1 neuroinvasion.
Topics: Male; Humans; Female; HIV Infections; HIV-1; Leukocytosis; HIV Seropositivity; RNA, Viral; Viral Load; Cerebrospinal Fluid
PubMed: 37916464
DOI: 10.1097/QAD.0000000000003777 -
American Journal of Hematology Jul 2017Monocytosis (absolute monocyte count, AMC ≥ 1 × 10 /L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the...
Monocytosis (absolute monocyte count, AMC ≥ 1 × 10 /L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)-defined PV, 55 (21%) patients displayed an AMC of ≥1 × 10 /L and 18 (7%) an AMC of ≥1.5 × 10 /L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs. 50% at AMC ≥1 × 10 /L) and TET2/SRSF2 mutations (57%/29% vs. 19%/1% at AMC ≥ 1.5 × 10 /L). In univariate analysis, AMC ≥1.5 × 10 /L adversely affected overall (OS; P = .004; HR 2.6, 95% CI 1.4-4.8) and myelofibrosis-free (MFFS; P = .02; HR 4.4, 95% CI 1.3-15.1) survival; during multivariable analysis, significance was borderline sustained for OS (P = .05) and MFFS (P = .06). Other independent risk factors for OS included unfavorable karyotype (P = .02, HR 3.39, 95% CI 1.17-9.79), older age (P < .0001, HR 3.34 95% CI 1.97-5.65), and leukocytosis ≥15 × 10 /L (P = .004, HR 2.04, 95% CI 1.26-3.29). In conclusion, in the current study, we encountered a higher than expected prevalence of monocytosis in patients with PV and the mutation profile and age distribution of PV patients with monocytosis is akin to those of patients with CMML and might partly contribute to their worse prognosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; DNA Mutational Analysis; Female; Humans; Kaplan-Meier Estimate; Karyotyping; Leukocyte Count; Leukocytosis; Male; Middle Aged; Monocytes; Mutation; Phenotype; Polycythemia Vera; Prognosis; Young Adult
PubMed: 28370365
DOI: 10.1002/ajh.24740 -
Annals of the American Thoracic Society Nov 2020
Topics: Alveolitis, Extrinsic Allergic; Bronchoalveolar Lavage; Humans; Lung Diseases, Interstitial; Lymphocytes; Lymphocytosis
PubMed: 33124908
DOI: 10.1513/AnnalsATS.202007-818ED -
Ugeskrift For Laeger Jan 2021Whooping cough is an infectious disease caused by Bordetella pertussis. Particularly children under the age of six months can be severely affected by the infection....
Whooping cough is an infectious disease caused by Bordetella pertussis. Particularly children under the age of six months can be severely affected by the infection. Severe leukocytosis may lead to thrombosis and pulmonary hypertension and eventually circulatory failure and death. This a case report of a three-week-old girl with malignant pertussis, who due to respiratory insufficiency was mechanically ventilated, and her severe leucocytosis was treated with exchange blood transfusion. Whooping cough may partially be prevented with efficient vaccination programmes.
Topics: Bordetella pertussis; Child; Female; Humans; Infant; Leukocytosis; Respiratory Insufficiency; Vaccination; Whooping Cough
PubMed: 33491624
DOI: No ID Found