Evaluation of Infection Risk Factors in Adult Hematologic Malignancy Patients

Peterson, S; Priddy, E.; Dong, Brian; Ghazi, C.; Dinglasan, Lu Anne V.

doi:10.1016/j.bbmt.2018.12.562

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many chronic, progressive conditions, hypoalbuminemia worsens along with the severity of inflammation and risk of mortality [ 63 ]. Preexisting hypoalbuminemia is a prognostic indicator of worse outcome for a broad spectrum of diseases ranging from medical conditions [ 64 , 65 , 66 ] to surgery [ 67 ]. Evidence in support of a prognostic role of serum albumin level is abundant and established for orthopedic [ 68 , 69 , 70 , 71 ], cardiovascular [ 72 , 73 ], gynecologic [ 74 , 75 ], and visceral surgery [ 76 , 77 , 78 ].…”

Section: Hypoalbuminemia and Disease Outcomesmentioning

confidence: 99%

“…The prognostic value of low serum albumin levels has been demonstrated not only for the development and complications of acute viral, bacterial, and fungal infections [ 95 ], but also for infectious complications in chronic conditions including malignant diseases [ 66 , 96 ], chronic inflammatory diseases [ 97 , 98 ], diabetes [ 95 ], hemodialysis [ 99 ], and solid organ transplantation [ 100 ]. In chronic infectious diseases, hypoalbuminemia is associated with disease reactivation/recurrence and secondary infections [ 101 , 102 , 103 ].…”

Section: Hypoalbuminemia and Prognosis In Infectionsmentioning

confidence: 99%

See 1 more Smart Citation

Hypoalbuminemia as Surrogate and Culprit of Infections

Wiedermann¹

2021

IJMS

155

View full text Add to dashboard Cite

Hypoalbuminemia is associated with the acquisition and severity of infectious diseases, and intact innate and adaptive immune responses depend on albumin. Albumin oxidation and breakdown affect interactions with bioactive lipid mediators that play important roles in antimicrobial defense and repair. There is bio-mechanistic plausibility for a causal link between hypoalbuminemia and increased risks of primary and secondary infections. Serum albumin levels have prognostic value for complications in viral, bacterial and fungal infections, and for infectious complications of non-infective chronic conditions. Hypoalbuminemia predicts the development of healthcare-associated infections, particularly with Clostridium difficile. In coronavirus disease 2019, hypoalbuminemia correlates with viral load and degree of acute lung injury and organ dysfunction. Non-oncotic properties of albumin affect the pharmacokinetics and pharmacodynamics of antimicrobials. Low serum albumin is associated with inadequate antimicrobial treatment. Infusion of human albumin solution (HAS) supplements endogenous albumin in patients with cirrhosis of the liver and effectively supported antimicrobial therapy in randomized controlled trials (RCTs). Evidence of the beneficial effects of HAS on infections in hypoalbuminemic patients without cirrhosis is largely observational. Prospective RCTs are underway and, if hypotheses are confirmed, could lead to changes in clinical practice for the management of hypoalbuminemic patients with infections or at risk of infectious complications.

show abstract

Section: Hypoalbuminemia and Disease Outcomesmentioning

confidence: 99%

Section: Hypoalbuminemia and Prognosis In Infectionsmentioning

confidence: 99%

Hypoalbuminemia as Surrogate and Culprit of Infections

Wiedermann¹

2021

IJMS

155

View full text Add to dashboard Cite

show abstract

“…Microbial infections are a significant contributing factor to the morbidity and mortality of acute leukemia (AL) patients, with a median incidence reaching around 27% [31]. This issue is particularly pronounced in immune-deficient patients, such as children with AL, and older patients with various types of leukemia [32][33][34][35][36]. For this reason, treatment requires the use of immunosuppressive drugs, which in turn increases the risk of microbial infections.…”

Section: Introductionmentioning

confidence: 99%

Lactoferricin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity

Lica,

Gucwa,

Heldt

et al. 2024

Molecules

View full text Add to dashboard Cite

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs) or antimicrobial peptides (AMPs), together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment, where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this study, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

show abstract

“…Microbial infections, varying by the type of hematologic malignancy, can contribute to approximately 7.1% of deaths in leukemia treatment (Chen et al, 2022). They are a noticeable concern in children with acute lymphoid leukemia (ALL) (O'Connor et al, 2014;Sezgin et al, 2022) as well as generally in older patients for different leukemia types (Safdar et al, 2011, Hassan et al, 2014Peterson et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation

Lica,

Heldt,

Wieczór

et al. 2023

Mol Pharmacol

View full text Add to dashboard Cite

Hematopoietic cell transplantation (HCT) is often considered a last resort leukemia treatment, fraught with limited success due to microbial infections, a leading cause of mortality in leukemia patients. To address this critical issue, we explored a novel approach by synthesizing antileukemic agents containing antibacterial substances. This innovative strategy involves conjugating fluoroquinolone antibiotics, such as ciprofloxacin (CIP) or levofloxacin (LVX), with the cell-penetrating peptide (CPP) transportan 10 (TP10). Here, we demonstrate that the resultant compounds display promising biological activities in preclinical studies. These novel conjugates not only exhibit potent antimicrobial effects but are also selective against leukemia cells. The cytotoxic mechanism involves rapid disruption of cell membrane asymmetry leading to membrane damage. Importantly, these conjugates penetrated mammalian cells, accumulating within the nuclear membrane without significant effect on cellular architecture or mitochondrial function. Molecular simulations elucidated the aggregation tendencies of TP10 conjugates within lipid bilayers, resulting in membrane disruption and permeabilization. Moreover, mass spectrometry analysis confirmed efficient reduction of disulfide bonds within TP10 conjugates, facilitating release and activation of the fluoroquinolone derivatives. Intriguingly, these compounds inhibited human topoisomerases, setting them apart from traditional fluoroquinolones. Remarkably, TP10 conjugates generated lower intracellular levels of reactive oxygen species (ROS) compared to CIP and LVX. The combination of antibacterial and antileukemic properties, coupled with selective cytostatic effects and minimal toxicity towards healthy cells, positions TP10 derivatives as promising candidates for innovative therapeutic approaches in the context of antileukemic HCT. This study highlights their potential in search of more effective leukemia treatments. SIGNIFICANCE STATEMENT Fluoroquinolones are commonly used antibiotics, while TP10 is a CPP with anticancer properties. In HCT, microbial infections are the primary cause of illness and death. Combining TP10 with fluoroquinolones enhanced their effects on different cell types. The dual pharmacological action of these conjugates offers a promising proof-of-concept solution for leukemic patients undergoing HCT. Strategically designed therapeutics, incorporating CPPs with antibacterial properties, have the potential to reduce microbial infections in the treatment of malignancies.

show abstract

Evaluation of Infection Risk Factors in Adult Hematologic Malignancy Patients

Cited by 3 publications

References 0 publications

Hypoalbuminemia as Surrogate and Culprit of Infections

Hypoalbuminemia as Surrogate and Culprit of Infections

Lactoferricin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity

Dual-Activity Fluoroquinolone-Transportan 10 Conjugates Offer Alternative Leukemia Therapy during Hematopoietic Cell Transplantation

Contact Info

Product

Resources

About