Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute Leukemia

Nucci, Márcio; Nouér, Simone Aranha; Anaissie, Elias

doi:10.1016/j.clml.2015.03.007

Cited by 13 publications

(11 citation statements)

References 69 publications

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“…Figure 5B). Both, REH-DX and PDX preclinical models demonstrated leukemic cell infiltration of brain, testis, and lung, organs known to be targets for leukemic infiltration [6, 27]. Importantly, infiltrated cells expressed cortactin, with the highest levels detected in B-ALL cells isolated from brain, testis, and lung (Fig.…”

Section: Resultsmentioning

confidence: 99%

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse

et al. 2018

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Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia. Here, we investigated cortactin expression and potential impact on infiltration and disease prognosis in childhood B-ALL. B-ALL cell lines and precursor cells from bone marrow (BM) and cerebrospinal fluid (CSF) of B-ALL patients indeed overexpressed cortactin. In CXCL12-induced transendothelial migration assays, transmigrated B-ALL cells had highest cortactin expression. In xenotransplantation models, only cortactinhigh-leukemic cells infiltrated lungs, brain, and testis; and they colonized more easily hypoxic BM organoids. Importantly, cortactin-depleted B-ALL cells were significantly less efficient in transendothelial migration, organ infiltration and BM colonization. Clinical data highlighted a significant correlation between high cortactin levels and BM relapse in drug-resistant high-risk B-ALL patients. Our results emphasize the importance of cortactin in B-ALL organ infiltration and BM relapse and its potential as diagnostic tool to identify high-risk patients and optimize their treatments.

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Section: Resultsmentioning

confidence: 99%

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse

et al. 2018

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“…In the present study, pneumonia was associated with early death by multivariate analysis. Pneumonia occurring at first fever in neutropenic patients is usually caused by bacteria (27). Gram-negative organisms (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli) are the leading agents recovered in blood cultures of neutropenic patients presenting with pneumonia (28,29).…”

Section: Discussionmentioning

confidence: 99%

Shock and Early Death in Hematologic Patients with Febrile Neutropenia

Guarana

Nucci

Nouér

2019

Antimicrob Agents Chemother

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Empirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data. In order to characterize the epidemiology of early death and shock in FN, we reviewed all episodes of FN from 2003 to 2017 at University Hospital, Federal University of Rio de Janeiro, and looked at factors associated with shock at first fever and early death (within 3 days from first fever) by univariate and multivariate analyses. Among 1,305 episodes of FN, shock occurred in 42 episodes (3.2%) and early death in 15 (1.1%). Predictors of shock were bacteremia due to Escherichia coli (odds ratio [OR], 8.47; 95% confidence interval [95% CI], 4.08 to 17.55; P < 0.001), Enterobacter sp. (OR, 7.53; 95% CI, 1.60 to 35.33; P = 0.01), and Acinetobacter sp. (OR, 6.95; 95% CI, 1.49 to 32.36; P = 0.01). Factors associated with early death were non-Hodgkin’s lymphoma (OR, 3.57; 95% CI, 1.18 to 10.73; P = 0.02), pneumonia (OR, 21.36; 95% CI, 5.72 to 79.72; P < 0.001), shock (OR, 11.64: 95% CI, 2.77 to 48.86; P = 0.01), and bacteremia due to Klebsiella pneumoniae (OR, 5.91; 95% CI, 1.11 to 31.47; P = 0.03). Adequate empirical antibiotic therapy was protective (OR, 0.23; 95% CI, 0.07 to 0.81; P = 0.02). Shock or early death was not associated with Gram-positive bacteremia; catheter-related, skin, or soft tissue infection; or inadequate Gram-positive coverage. These data challenge guideline recommendations for the empirical use of vancomycin at first fever in neutropenic patients.

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“…The clinico-radiologic syndrome of fever with reticulonodular shadows and lymphadenopathy may have a range of differential diagnosis in the setting of acute leukemia patients and accurate localization of involved sites is necessary to guide FNACs [26]. PET CT scan was able to guide the site of biopsy and pick up occult sites of TB in two of our patients of AML who developed PUO after AML induction therapy.…”

Section: Discussionmentioning

confidence: 78%

Analysis of Clinical Profile and Outcome of Tuberculosis in Patients with Acute Leukemia

Jain

Prakash

Singh

et al. 2017

Indian J Hematol Blood Transfus

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Patients with acute leukemia (AL) are predisposed to develop infections including tuberculosis (TB). The risk is specifically higher in patients from TB endemic areas. Patients (≥12 years) with AL treated between January-2014 to January-2017 who developed TB were reviewed. Patients were classified into three groups: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and acute promyelocytic leukemia (APML) and a systematic analysis of clinical features and outcomes was conducted. Over the study period, 26 patients of AL developed TB. The median time to diagnosis of TB was 8 weeks (0-432 weeks) following the diagnosis of AL and it was comparable between the three leukemia groups. The diagnosis of TB required alteration of anti-leukemia therapy in 26.9% patients and rescheduling in another 42.3% patients. Therapy alteration/rescheduling were more frequent in patients with AML as compared to ALL and APML ( < 0.03, <0.04). Disseminated TB was more common in AML patients ( < 0.016). ATT could be successfully administered in 86.9% patients with improvement of TB. The incidence of ATT induced hepatitis was 34.9%. Mortality was directly attributable to TB in 10% patients. Managing tuberculosis remains a challenge during treatment of acute leukemia. With this analysis, we advocate for a need of early suspicion and evaluation for TB in patients receiving treatment for acute leukemia. Rescheduling and or alteration of anticancer therapy due to TB is associated with significantly higher mortality. Therefore, in carefully selected cases, antileukemia therapy should continue after starting ATT as early as possible.

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Distinguishing the Causes of Pulmonary Infiltrates in Patients With Acute Leukemia

Cited by 13 publications

References 69 publications

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse

High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse

Shock and Early Death in Hematologic Patients with Febrile Neutropenia

Analysis of Clinical Profile and Outcome of Tuberculosis in Patients with Acute Leukemia

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