Serious Infections Drive Major Hospital Costs in CLL

As targeted therapies extend survival and reshape treatment patterns, understanding the cost drivers in chronic lymphocytic leukemia (CLL) has become increasingly important for policymakers, clinicians, and payers, according to a new population‑based analysis from Victoria, Australia, published in Cancer Medicine.¹

The authors’ findings highlight the substantial financial burden that serious infections place on patients with CLL and the public health system.^2,3

Infections have long been recognized as a leading cause of morbidity and mortality in CLL due to disease‑related immune dysfunction and treatment‑induced immunosuppression, the authors explain. They also may represent one of the most expensive complications of care in this space. Yet, although it is known that the economic burden of CLL is rising globally, driven by longer survival, increased treatment exposure, and the introduction of high‑cost targeted therapies, the true economic consequences of infection in CLL have been poorly quantified. The study authors sought to fill this gap by estimating the excess hospital costs associated with serious infections and other major cost drivers, including immunoglobulin replacement therapy (IgRT) and in‑hospital anticancer treatment.

Why and How This Study Was Conducted

There are no standardized guidelines for infection prophylaxis in CLL, and the role of IgRT remains controversial. Understanding the true cost of infections is essential for evaluating prophylactic strategies and optimizing resource allocation, the authors stressed.

The researchers conducted a retrospective, longitudinal cost analysis using linked cancer registry, death registry, and administrative hospital datasets from Victoria, Australia. Their study included 3705 adult patients with a new diagnosis of CLL admitted to a public hospital between July 2016 and June 2022; private hospitals were not included because they did not provide cost data. For this cohort, serious infections were defined as multiday, infection‑related hospitalizations identified through the World Health Organization International Statistical Classification of Diseases and Related Health Problems, Tenth Edition, Australian Modification and Australian refined diagnosis-related groups codes.

Costs were calculated and adjusted to 2024 Australian dollars, and generalized linear models were used to estimate the excess monthly cost attributable to infections, IgRT, anticancer treatment, comorbidities, and other factors.

Key Study Findings

The study cohort reflected a typical real-world CLL population, in that most patients (55.5%) were aged 70 years and older. A majority also were male patients (64.3%), and 51.6% had a mild comorbidity burden (0-2) per the Charlson Comorbidity Index, while 9.3% had a moderate (3-4) or severe (5 or more) comorbidity burden. A total of 45.6% (n = 1689) of the patients experienced at least one serious infection during follow-up, which was a mean of 3.8 (1.9) years, with a mean (SD) of 0.5 (1.4) infections per individual, but only 9% received IgRT and 26.2% received in‑hospital anticancer treatment. Close to one-third of patients (28.5%) died during follow‑up.

The authors determined that serious infections in the setting of CLL are extremely costly. In their analysis:

• A serious infection increased monthly hospital costs by AU$22,905 (US$15,829), and these costs remained elevated for 6 months after the infection
• Total cost per serious infection episode (index month + 6 months) came out to AU$27,759 (US$19,184)
• IgRT and anticancer treatment drove costs up toAU$3288 (US$2772) and AU$5223 (US$3609) per patient per month, respectively

Given that IgRT is typically administered monthly, the authors explained, annual IgRT costs came in at AU$39,456 (US$27,267), raising questions about cost-effectiveness in patients at lower infection risk.

Costs peaked at diagnosis and remained elevated near the end of life, they also found. In the month of diagnosis, costs totaled AU$4168 (US$2880), and in the last month of life, AU$2275 (95% CI, $544-$4006). Overall, the total excess cost in a patient’s final 6 months was AU$10,615 (US$7336), and patients with severe comorbidities had substantially higher monthly costs compared with those with mild or no recorded comorbidities.

Real‑World Implications

This study provides some of the clearest evidence to date that serious infections, not anticancer drugs, may be the single largest driver of hospital costs in CLL.

For clinicians, this could mean that infection prevention strategies should be prioritized, especially for high‑risk patients, and that IgRT may be cost‑effective only in carefully selected individuals, given its high monthly cost and uncertain benefit. For policymakers and payers, infection‑related hospitalizations represent a major, potentially preventable cost burden; economic models evaluating prophylactic interventions (eg, IgRT, vaccines, and antimicrobial prophylaxis) should incorporate these real‑world cost estimates. For health systems, the concentration of costs at diagnosis and end of life highlights opportunities for targeted care pathways, early intervention, and palliative care integration.

Still, there are limitations on these results. The study was retrospective and used administrative data, so key prognostic and other unknown compounding factors could have influenced the results. How infection diagnoses were coded could have led to overestimation of infection events. Only public hospital data were available, which could have led to an underestimation of the true costs to patients who received care at public and private hospitals.

“Further studies including costs to the patient and health care utilization in the outpatient setting are needed,” the authors concluded, “to fully ascertain the cost of infections and the overall cost of cancer care in patients with CLL.”

References

1. de Albornoz SC, Arnolda R, Higgins AM, Wood EM, McQuilten ZK, Petrie D. Cost of serious infections in chronic lymphocytic leukemia. Cancer Med. 2026;15(2):e71397. doi:10.1002/cam4.71397
2. Diella L, Bavaro DF, Loseto G, et al. Current therapies for chronic lymphocytic leukemia: risk and prophylaxis strategies for secondary/opportunistic infections. Expert Rev Hematol. 2023;16(4):267-276. doi:10.1080/17474086.2023.2192918
3. Guarana M, Nucci M. Infections in patients with chronic lymphocytic leukemia. Hematol Transfus Cell Ther. 2023;45(3):387-393. doi:10.1016/j.htct.2023.05.006