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Parainfluenza virus infections in children with hematologic malignancies.

ABSTRACT: Parainfluenza virus (PIV) infections are an important cause of morbidity in children with upper or lower respiratory tract infection (URTI and LRTI, respectively). However, the epidemiology of PIV infections in children with cancer has not been well studied.This retrospective study sought to determine the epidemiology of PIV infections and risk factors for progression to an LRTI in 1381 children diagnosed with leukemia or lymphoma, between 2000 and 2009.PIV infections were diagnosed in 83 (10%) of 820 children tested for respiratory infections. PIV type 3 accounted for 49 (61%) of the PIV infections. Of the 83 infections, 75 (90%) were community acquired. Children less than 2 years of age were more likely to have PIV infection (P = 0.002; odds ratio, 2.69; 95% confidence interval, 1.5-4.8). PIV infections were more common in children with acute lymphoblastic leukemia as compared with other malignancies (P < 0.0001; odds ratio, 4.13; 95% confidence interval, 2.37-7.21). The majority of patients, 66 (80%), had URTI. Children with LRTI were a median age of 27 months as compared with 56 months for children with URTI (P = 0.005). Fever with severe neutropenia was more common in patients with LRTI than with URTI (P = 0.02). LRTI was significantly associated with absolute neutrophil count <500 cells/?L (P = 0.002) and absolute lymphocyte count <100 cells/?L (P = 0.008) at onset of PIV infection. There was no mortality attributed to PIV infections, although 3 children required mechanical ventilation for respiratory failure due to PIV infection.PIV was the second most common respiratory viral infection in this population after influenza (A and B). Young children were more likely to have PIV infection and LRTI. Severe neutropenia and lymphopenia were associated with LRTI.

SUBMITTER: Srinivasan A

PROVIDER: S-EPMC3196524 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Parainfluenza virus infections in children with hematologic malignancies.

Srinivasan Ashok A Wang Chong C Yang Jie J Inaba Hiroto H Shenep Jerry L JL Leung Wing H WH Hayden Randall T RT

The Pediatric infectious disease journal 20111001 10

<h4>Background</h4>Parainfluenza virus (PIV) infections are an important cause of morbidity in children with upper or lower respiratory tract infection (URTI and LRTI, respectively). However, the epidemiology of PIV infections in children with cancer has not been well studied.<h4>Methods</h4>This retrospective study sought to determine the epidemiology of PIV infections and risk factors for progression to an LRTI in 1381 children diagnosed with leukemia or lymphoma, between 2000 and 2009.<h4>Res ...[more]

PMID: 21540759

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Project description:The phosphatidylinositiol 3-kinase (PI3K), AKT, mammalian target of rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR) is frequently dysregulated in disorders of cell growth and survival, including a number of pediatric hematologic malignancies. The pathway can be abnormally activated in childhood acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML), as well as in some pediatric lymphomas and lymphoproliferative disorders. Most commonly, this abnormal activation occurs as a consequence of constitutive activation of AKT, providing a compelling rationale to target this pathway in many of these conditions. A variety of agents, beginning with the rapamycin analogue (rapalog) sirolimus, have been used successfully to target this pathway in a number of pediatric hematologic malignancies. Rapalogs demonstrate significant preclinical activity against ALL, which has led to a number of clinical trials. Moreover, rapalogs can synergize with a number of conventional cytotoxic agents and overcome pathways of chemotherapeutic resistance for drugs commonly used in ALL treatment, including methotrexate and corticosteroids. Based on preclinical data, rapalogs are also being studied in AML, CML, and non-Hodgkin's lymphoma. Recently, significant progress has been made using rapalogs to treat pre-malignant lymphoproliferative disorders, including the autoimmune lymphoproliferative syndrome (ALPS); complete remissions in children with otherwise therapy-resistant disease have been seen. Rapalogs only block one component of the pathway (mTORC1), and newer agents are under preclinical and clinical development that can target different and often multiple protein kinases in the PI3K/AKT/mTOR pathway. Most of these agents have been tolerated in early-phase clinical trials. A number of PI3K inhibitors are under investigation. Of note, most of these also target other protein kinases. Newer agents are under development that target both mTORC1 and mTORC2, mTORC1 and PI3K, and the triad of PI3K, mTORC1, and mTORC2. Preclinical data suggest these dual- and multi-kinase inhibitors are more potent than rapalogs against many of the aforementioned hematologic malignancies. Two classes of AKT inhibitors are under development, the alkyl-lysophospholipids (APLs) and small molecule AKT inhibitors. Both classes have agents currently in clinical trials. A number of drugs are in development that target other components of the pathway, including eukaryotic translation initiation factor (eIF) 4E (eIF4E) and phosphoinositide-dependent protein kinase 1 (PDK1). Finally, a number of other key signaling pathways interact with PI3K/AKT/mTOR, including Notch, MNK, Syk, MAPK, and aurora kinase. These alternative pathways are being targeted alone and in combination with PI3K/AKT/mTOR inhibitors with promising preclinical results in pediatric hematologic malignancies. This review provides a comprehensive overview of the abnormalities in the PI3K/AKT/mTOR signaling pathway in pediatric hematologic malignancies, the agents that are used to target this pathway, and the results of preclinical and clinical trials, using those agents in childhood hematologic cancers.

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Parainfluenza virus infections in children with hematologic malignancies.

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Parainfluenza virus infections in children with hematologic malignancies.

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