A review of the infection pathogenesis and prophylaxis recommendations in patients with chronic lymphocytic leukemia

Abstract

The majority of patients with CLL will suffer from infections during their disease, accounting for approximately 60% of deaths in CLL. Patients are predisposed to infection due to immune defects related to the primary disease, and as a result of therapy. The range of infectious complications has evolved alongside therapeutic advances in the treatment of CLL. More recently several novel therapeutic compounds have been introduced in CLL, whose unique safety profiles will probably have an impact on the prophylaxis and management of infections in these patients. Areas covered: This review describes the pathogenesis of infections due to intrinsic CLL or therapy-related immunosuppression, and elightens the importance of proactive and reactive infection management as a key focus of patient care. Infections related to conventional chemotherapy, immunochemotherapy with monoclonal antibodies, target therapies with B-cell receptor pathway inhibitors and Bcl-2 antagonists are reviewed. Expert commentary: Despite the importance of infection management and prevention in high-risk patients, there are only limited infection risk-assessment guidelines that can be easily used in clinical practice to guide more appropriate infection prophylaxis and its management. Here we provide an overview of suggested prophylaxis management of infection, and include key prophylactic interventions that we feel should be performed in CLL patients routinely.

A population‐based study on serious inpatient bacterial infections in patients with chronic lymphocytic leukemia and their impact on survival

“…There has been a lack of risk assessment tools for infections in CLL patients, although recently 14 a nationwide Danish study introduced an explainable machine learning model to identify CLL patient at high risk for infection. In recent years, the guidelines on early empiric treatment in febrile neutropenia have improved 17 ; however, there has been a lack of international consensus on antibiotic prophylaxis for bacterial infections, 16,30 although individual national and local institutions have recommended prophylaxis in specific circumstances.…”

Pharmacists’ Role in Managing Patients with Chronic Lymphocytic Leukemia

“…Infectious complications during CLL therapy can generally be divided into early and late phases [7]. In the early period, which occurs in the first months of therapy, persistent neutropenia increases the risk of bacterial infections.…”

“…Growth factor support can be considered in patients with risk factors for prolonged neutropenia, such as renal or liver dysfunction. In the late period, which can last up to 2 years or more after therapy, T-cell dysfunction may occur, increasing the risk of both bacterial and opportunistic infections, including Listeria monocytogenes, Pneumocystis jiroveci pneumonia (PCP), cytomegalovirus (CMV), herpes simplex virus (HSV), and mycobacteria [7].…”

“…Pharmacists also ensure that patients receive appropriate infection prophylaxis and adequate monitoring for toxicities associated with each therapy. Each of the different therapeutic options, ranging from the anti-CD20 monoclonal antibodies to various oral targeted agents, have distinct recommendations for infection prophylaxis [7]. Tyrosine kinase inhibitors (TKIs), PI3K inhibitors, and venetoclax are all associated with a unique set of adverse effects and monitoring parameters [1].…”

Rare concurrent indolent B-cell lymphoma and plasmablastic transformation of myeloma

“…A background of immune suppression due to HIV or other causes is related to the development of PBL 10 . Low-grade B-cell neoplasms, such as CLL, SMZL and HCL, are associated with a frequent incidence of immune suppression or immune disorder 11 - 13 . Indeed, patients with concomitant B-CLL and multiple myeloma often have a more unfavorable clinical course than those with multiple myeloma alone, presenting adverse prognostic features and early death due to myeloma progression.…”