High risk of invasive fungal infections in adult acute lymphoblastic leukemia patients receiving induction and salvage chemotherapy

Keng, Ming-Hsun Bryan; Keng, Hui-Lin Clara; Tan, Ban-Hock; Wong, Gee-Chuan

doi:10.1080/10428194.2016.1267351

Cited by 3 publications

(1 citation statement)

References 6 publications

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“…6 In the clinic, patients with acute leukaemia are considered immunocompromised and face a high risk of developing fungal infections. 7,8 Triazoles are the standard of care in patients with acute leukaemia receiving remission induction therapy or allogeneic stem cell transplantation. 9,10 Posaconazole is a second-generation triazole agent with broad-spectrum antifungal activity (Figure 1B).…”

Section: Introductionmentioning

confidence: 99%

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Yang¹,

Zhang²,

Wang³

et al. 2021

DDDT

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Background and Aim: Dasatinib is approved for the treatment of leukaemia worldwide.Triazole agents such as posaconazole may be used for the control of secondary fungal infection with leukaemia. This work aimed to develop a bioanalytical method to study the potential interaction between dasatinib and posaconazole. Methods: An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was established to measure the plasma concentrations of dasatinib and posaconazole in rats simultaneously. Simple protein precipitation with acetonitrile was applied to extract dasatinib and posaconazole in samples. The chromatographic separation of analytes was conducted on an UPLC BEH C18 column using a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile. Dasatinib and posaconazole were monitored in positive ion mode with the following mass transition pairs: m/z 488.2→401.1 for dasatinib and m/z 701.3→683.4 for posaconazole. The method was successfully applied for pharmacokinetic interaction between dasatinib and posaconazole. Results: The established method expressed good linearity in 1-1000 ng/mL of dasatinib and 5-5000 ng/mL of posaconazole, with limit of detection was 1 ng/mL and 5 ng/mL, respectively. Methodology validations, including accuracy, precision, matrix effect, recovery, and stability, met the US Food and Drug Administration (FDA) acceptance criteria for bioanalytical method validation. Dasatinib strongly inhibited the clearance of posaconazole in vivo, while posaconazole expressed no significant effect on the pharmacokinetics of dasatinib. Conclusion: Dasatinib alters the pharmacokinetics of posaconazole. Attention should be paid to the unexpected risk of adverse clinical outcomes when posaconazole is coadministered with dasatinib.

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Section: Introductionmentioning

confidence: 99%

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Yang¹,

Zhang²,

Wang³

et al. 2021

DDDT

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Prophylaxis for aspergillosis in patients with haematological malignancies: pros and cons

Busca

Pagano

2018

Expert Review of Anti-infective Therapy

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Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. Nevertheless, invasive fungal infections (IFI) represent a major hindrance to the favorable outcome of patients with hematologic malignancies. According to these observations, an appropriate prevention of IFI occurring in hematologic patients should be considered of paramount importance. However, the wide use of antifungal agents may facilitate the emergence of resistance and may be associated to the occurrence of severe adverse events and eventually may significantly increase the cost of therapeutic procedures. Areas covered: The aim of present review is to analyze advantages and disadvantages of primary antifungal prophylaxis (PAP) in hematologic patients. Expert commentary: Patients with AML/MDS undergoing intensive chemotherapy and patients receiving stem cell transplantation are at high risk of IFI, and therefore may benefit form PAP, although several additional factors should be carefully evaluated in our decision-making approach, including the local epidemiology and the prompt availability of diagnostic facilities. The advent of new treatment options for hematologic patients such as target therapies might facilitate the rise of new risk categories so far underestimated.

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Acute Lymphoblastic Leukemia and Invasive Mold Infections: A Challenging Field

Stafylidis

Diamantopoulos

Athanasoula

et al. 2022

JoF

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Acute lymphoblastic leukemia (ALL) patients comprise a highly immunocompromised group due to factors associated either with the treatment or the disease itself. Invasive mold infections (IMIs) are considered to be responsible for higher morbidity and mortality rates in patients with hematologic malignancies, including ALL. Defining the exact incidence of IMIs in ALL patients has been rather complicated. The available literature data report a highly variable incidence of IMIs, ranging from 2.2% to 15.4%. Although predisposing factors for IMIs in the setting of ALL are ill-defined, retrospective studies have indicated that a longer duration of neutropenia, treatment with high-dose corticosteroids, and a lack of antimold prophylaxis are associated with an increased risk of IMIs. Additionally, the influence of novel ALL treatments on the susceptibility to fungal infections remains obscure; however, initial data suggest that these treatments may induce prolonged neutropenia and thus an increased risk of IMIs. Administering primary antimold prophylaxis in these patients has been challenging since incorporating azole antifungal agents is troublesome, considering the drug-to-drug interactions (DDIs) and increased toxicity that may occur when these agents are coadministered with vincristine, a fundamental component of ALL chemotherapy regimens. Isavuconazole, along with several novel antifungal agents such as rezafungin, olorofim, and manogepix, may be appealing as primary antimold prophylaxis, given their broad-spectrum activity and less severe DDI potential. However, their use in ALL patients needs to be investigated through more clinical trials. In summary, this review outlines the epidemiology of IMI and the use of antifungal prophylaxis in ALL patients.

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High risk of invasive fungal infections in adult acute lymphoblastic leukemia patients receiving induction and salvage chemotherapy

Cited by 3 publications

References 6 publications

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Development of UPLC-MS/MS Method for Studying the Pharmacokinetic Interaction Between Dasatinib and Posaconazole in Rats

Prophylaxis for aspergillosis in patients with haematological malignancies: pros and cons

Acute Lymphoblastic Leukemia and Invasive Mold Infections: A Challenging Field

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