OBJECTIVES:Peripheral neuropathy (PN) is considered a frequent complication of Waldenström's macroglobulinemia (WM). Establishing a causal relationship between PN and WM is complicated by confounding factors such as age-related axonal loss and diabetes. This scoping review aims to summarize the current evidence on WM-associated PN with a focus on prevalence, phenotype, and disability. METHODS:We searched PubMed, Embase, Web of Science, CINAHL, and Cochrane Library and included studies describing either prevalence, phenotype, and/or disability of adults with WM and PN. RESULTS:Thirty-four studies were eligible for inclusion where most studies were retrospective case series. The most frequently reported phenotype was a sensory axonal PN while demyelinating PN only ranged from 8% to 37.5% in unselected WM cohorts. Eight different disability scales were used, primarily in anti-MAG studies. Prevalence of WM-associated PN ranged from 0% to 52% where small cross-sectional studies reported higher prevalence than larger retrospective studies. CONCLUSION:Our findings suggest PN in WM is a frequent complication often presented as a sensory axonal PN. Interpretation of results is confounded by referral bias, lack of PN definition, missing clinical and electrophysiological examination, and limited comparable disability measures across PN subtypes. This review underscores the need for a definition of WM-associated PN.
BACKGROUND:T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive mature T-cell malignancy with limited therapeutic options. Alemtuzumab remains the backbone of therapy, and fit responders are consolidated with allogeneic stem cell transplantation (alloSCT). However, contemporary population-level outcomes remain poorly defined. METHODS:All T-PLL cases diagnosed between 2001 and 2023 were identified from the nationwide Netherlands Cancer Registry. Overall survival (OS) and survival after relapse (OS2) were analyzed in 220 patients. Detailed treatment-line data were available for patients diagnosed from 2014 onward (n = 120), enabling assessment of treatment sequencing, response, and progression-free survival (PFS). RESULTS:Median age at diagnosis was 71 years; 56% were male. Overall, 54% received systemic therapy, of whom 25% underwent transplantation. Median OS was 13.5 months; 2- and 5-year OS were 36% and 10%, with no improvement over time. Alemtuzumab was the predominant frontline therapy and was associated with higher response and survival than other regimens. Consolidation with alloSCT provided the greatest likelihood of durable disease control, although only one-third of treated patients were eligible. Survival after relapse remained poor (median OS2, 5-7 months), and later treatment lines rarely produced durable benefit. Nearly half of patients were initially managed with observation; long-term survival remained limited after progression. CONCLUSIONS:Alemtuzumab followed by alloSCT remains the most effective strategy for fit patients with T-PLL, yet long-term survival is uncommon and has not improved over two decades. High relapse rates and poor salvage outcomes underscore the need for novel targeted and immune-based approaches and optimized post-remission strategies.
The Lymph2Cx assay has played a key role in the clinical translation of the diffuse large B-cell lymphoma (DLBCL) molecular classification for cell-of-origin (COO) determination, as mandated by the 2017 Revised WHO Classification. Applicable to routine formalin-fixed paraffin-embedded biopsies, Lymph2Cx has shown high concordance with gold-standard gene expression profiling (GS) performed on fresh/frozen samples. However, conventional concordance metrics may overlook systematic bias. We first reassessed agreement between Lymph2Cx and GS using Bland-Altman analysis and Cohen's kappa. Subsequently, the prognostic impact of the cell-of-origin of diffuse large B-cell lymphoma as determined by Lymph2Cx was compared with that as determined by GS. This was done by assembling large cohorts of publicly available, clinically annotated cases, analyzed by Lymph2Cx or GS, comprising a total of 2321 cases. Lymph2Cx consistently underestimated the frequency of the activated B-cell-like (ABC) subtype, misclassifying a subset of ABC cases as germinal center B-cell-like (GCB) or unclassified (UNC). While ABC DLBCL retained its adverse prognosis across cohorts, GCB and UNC groups defined by Lymph2Cx showed higher hazard ratios than their GS-defined counterparts, consistent with redistribution of higher-risk ABC cases. Overall, although Lymph2Cx remains a valuable tool for routine COO determination, our findings indicate the need for further refinement to improve categorical accuracy, particularly for the ABC subtype, to support optimal clinical risk stratification.
Trauma-induced coagulopathy is a maladaptive, multifactorial response to severe injury that affects approximately one quarter of severely injured patients and substantially increases mortality. It arises from combined tissue injury and shock and is characterized by endothelial dysfunction, platelet abnormalities, fibrinogen depletion, and dysregulated fibrinolysis, with thrombin generation typically preserved early and reduced only later, evolving through early hypocoagulable, balanced, and later hypercoagulable phases. Recognition of trauma endotheliopathy, including glycocalyx shedding and the von Willebrand factor-ADAMTS-13 axis, has broadened understanding beyond simple consumption and dilution. Viscoelastic hemostatic assays, thromboelastography and rotational thromboelastometry, characterize clot initiation, propagation, strength, and lysis in near-real time and can detect fibrinolysis, fibrinogen deficiency, and platelet dysfunction that conventional tests miss; early clot amplitude parameters enable rapid, goal-directed decisions, although the largest randomized trial to date did not demonstrate a mortality benefit over conventional testing, and most thresholds remain expert-derived and platform-specific. Contemporary therapy focuses on damage-control resuscitation with permissive hypotension, balanced ratio-based transfusion, early tranexamic acid, calcium replacement, and targeted rather than empiric fibrinogen replacement, with recombinant activated factor VII reserved for rescue. Preinjury antithrombotic therapy and liver disease call for agent-specific adjustments, summarized in an accompanying reference table. This review synthesizes the mechanisms, viscoelastic diagnosis, and goal-directed treatment of trauma-induced coagulopathy and highlights persistent knowledge gaps, including the significance of fibrinolysis shutdown, endotheliopathy-directed therapy, and the optimal timing of venous thromboembolism prophylaxis and resumption of antithrombotic therapy.
BACKGROUND:The JAK2V617F mutation is a driver mutation in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and myelofibrosis. Recent studies have revealed a significant prevalence of JAK2V617F as clonal hematopoiesis of indeterminate potential (CHIP) in the general population, particularly in individuals over 50 years. CHIP-JAK2V617F carriers exhibit increased mortality, driven by cardiovascular diseases and cancer. Given the prothrombotic and inflammatory nature of JAK2V617F, we investigated its prevalence in patients with acute coronary syndrome (ACS). METHODS:We screened 526 consecutive ACS patients for the JAK2V617F mutation using sensitive droplet digital PCR (ddPCR) and allele-specific real-time quantitative PCR (RQPCR). Clinical and laboratory data were analyzed to assess associations. RESULTS:The JAK2V617F mutation was detected in 6.1% (32/526) of ACS patients, significantly higher than the general population prevalence (3.1%). CONCLUSION:Our findings suggest that JAK2V617F may contribute to ACS pathogenesis through prothrombotic and inflammatory mechanisms. Screening for JAK2V617F in high-risk cardiovascular patients could identify individuals who may benefit from targeted therapies.
Eosinophilia, defined as an absolute eosinophil count (AEC) of ≥ 0.5 × 109/L, is a frequently encountered finding with a vast spectrum of potential underlying etiologies. Hypereosinophilia (HE) is defined as AEC > 1.5 × 109/L and may become life-threatening when eosinophil-induced organ damage occurs, defining the hypereosinophilic syndrome (HES). Among the many causes of HE, rare hematological malignancies, in particular the "myeloid/lymphoid neoplasms (MLN) with eosinophilia and tyrosine kinase (TK) gene fusions," represent phenotypically and prognostically heterogeneous and challenging entities. For this reason, the evaluation of HE constitutes a diagnostic and therapeutic challenge. In this review, we provide a concise overview of eosinophil biology, highlight their physiological role as regulators of immunity, tissue homeostasis, and inflammation, their involvement in diseases affecting nearly all organ systems, and in hematological malignancies in particular. Furthermore, we present a practical, stepwise diagnostic approach to HE, emphasizing early recognition of eosinophil-mediated organ dysfunction to initiate timely treatment, as well as red flags that should raise further hematologic evaluation, including molecular and cytogenetic investigations to identify an underlying clonal disorder. Treatment strategies depend on the underlying etiology and range from supportive care, over corticosteroids to targeted biological therapies and tyrosine kinase inhibitors (TKIs).
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by a defect of glycosylphosphatidyl-anchored proteins, leading to an uncontrolled complement-mediated hemolysis. The advent of complement inhibitors in clinical practice radically changed patients' outcomes and survival. Despite this significant progress, numerous unmet needs persist in clinical practice. A group of Italian experts explored the main challenges currently associated with PNH diagnosis and monitoring and reached a consensus on screening, diagnosis, initial work-up, and monitoring. The following core questions were examined: (i) Which patients need to be tested? (ii) Which test to use, and how do we define positivity? (iii) Which workup is requested for patients with a newly detected PNH clone? (iv) Which monitoring in untreated patients? (v) Which monitoring in C-terminal-inh and C-proximal inh? Each specific clinical question was framed according to the GRADE format. Overall, flow-cytometry for PNH detection was recommended in patients presenting with two or more suggestive signs or symptoms and/or with hematologic conditions known to be associated with PNH clones, including DAT-negative hemolysis, idiopathic venous thrombosis (particularly at atypical sites), and primary bone marrow dysfunction (such as aplastic anemia or myelodysplastic syndrome). A high-sensitivity flow cytometry test in neutrophils and erythrocytes should be preferred (lower limit of quantification 0.01%). Baseline assessment of disease activity (i.e., LDH > 1.5×ULN and PNH signs/symptoms), thrombotic risk, bone marrow (BM) features and imaging for organ dysfunction are suggested. Monitoring comprises blood counts and hemolytic markers with frequency depending on anemia severity and symptoms, as well as annual PNH clone retesting, BM reevaluation in case of cytopenias, and constant education about infectious risk and breakthrough hemolysis in patients on treatment.
We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.
Acute myeloid leukemia (AML) is an aggressive and heterogeneous hematological malignancy in which treatment resistance and relapse remain major causes of mortality. Extracellular vesicles (EVs) contribute to AML progression by mediating communication among leukemic blasts, leukemia stem cells, hematopoietic stem and progenitor cells, stromal and endothelial cells, and immune-cell populations. Experimental studies indicate that AML-associated EVs can remodel the bone marrow niche, suppress normal hematopoiesis, impair antileukemic immune responses, promote leukemic-cell survival, and facilitate drug resistance. Their surface markers and molecular cargo, including proteins, miRNAs, mRNAs, DNA, lipids, and metabolites, have also prompted investigation into their use as liquid-biopsy biomarkers. Candidate EV-based markers include particle abundance, blast-associated antigens, TGF-β1, FLT3-ITD and NPM1 alterations, and several circulating miRNAs. However, most biomarker studies remain small, heterogeneous, and insufficiently compared with established measurable residual disease assays. Therapeutic strategies involving inhibition of EV release or uptake, EV-based immunotherapy, and engineered EVs for drug or RNA delivery are also being explored, but current evidence is predominantly preclinical. Clinical translation is further limited by inconsistent terminology, variable isolation and characterization methods, contamination by non-vesicular particles, and a lack of prospective multicenter validation. This review summarizes the biological roles, biomarker potential, therapeutic applications, and methodological challenges of EVs in AML and highlights the priorities required for their future clinical development.
OBJECTIVES:To investigate circulating regulatory T cells (Tregs) in children with autoimmune neutropenia (AIN) and chronic idiopathic neutropenia (CIN) and evaluate their associations with clinical and laboratory features of neutropenia. METHODS:Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were collected from 69 participants. Anti-neutrophil antibody testing included flow cytometry Granulocyte Immunofluorescence Testing (fGIFT) and Granulocyte Agglutination Testing (GAT). Subjects were classified as AIN upon positive assays (n = 40), CIN upon negative assays (n = 19), and controls healthy children (n = 10). Personal history, infection susceptibility, and laboratory tests were recorded. Tregs were measured through flow cytometry, while FOXP3 expression was measured through Western blot. RESULTS:Tregs percentages (Tregs%) and absolute values were significantly lower among AIN and CIN than controls (Tregs%: p < 0.01 for AIN CIN, Tregs: p < 0.01 for AIN, p = 0.01 for CIN- Mann- Whitney U test). FOXP3 expression was maintained. Tregs were analogous with white blood cells (ρ = 0.43, p < 0.01 Spearman's) and lymphocytes (ρ = 0.42, p < 0.01) among children with AIN, while Tregs levels were associated infection severity among children with CIN. CONCLUSIONS:Children with AIN and CIN exhibit reduced circulating Tregs, while these values are associated with clinical and laboratory aberrations, suggesting a potential contribution in the immunopathogenesis of neutropenia.
Infectious complications are increasingly recognized as a crucial aspect of the clinical management of patients with Myelofibrosis. Infection susceptibility is multifactorial and reflects the interplay between disease-related immune dysregulation, treatment-associated immunomodulation, and patient-specific factors such as age, comorbidities, and prior therapies. Myelofibrosis is characterized by a chronic inflammatory state and impaired innate and adaptive immunity, including dysfunction of natural killer cells, dendritic cells, and T lymphocytes. The introduction of JAKis has significantly improved disease outcomes, while these agents may further modulate immune responses through inhibition of the JAK-STAT pathway. Evidence from clinical trials and real-world studies indicates that bacterial infections are common, while viral reactivations, particularly herpes zoster, represent a consistent complication of JAKi therapy. Opportunistic infections are less frequent but clinically relevant. In our view, infection risk in myelofibrosis should be considered an intrinsic component of disease biology and treatment. A risk-adapted approach integrating baseline assessment, vaccination, and close clinical monitoring is warranted. Future efforts should focus on biomarker-driven risk stratification and tailored preventive strategies to optimize outcomes in patients receiving JAKis.
The correlation between bone marrow fibrosis (BMF) and extramedullary disease has yet to be fully elucidated in patients with newly diagnosed multiple myeloma. Therefore, we aimed to analyze the incidence of BMF in newly diagnosed multiple myeloma patients and evaluate the relationship between BMF and synchronous soft tissue extramedullary involvement at diagnosis. A retrospective chart review was conducted on a total of 356 patients with multiple myeloma. Patients' clinical characteristics, treatment outcomes, and histological features were systematically collected. The degree of BMF was graded according to the World Health Organization criteria. Patients with Grade 2 and 3 BMF were classified into the fibrosis group, whereas those with Grade 0 or 1 were categorized into the non-fibrosis group. Extramedullary disease was defined as soft tissue tumors arising from hematogenous spread without any contiguous contact with bony structures. Finally, clinical and laboratory parameters were compared between the fibrosis and non-fibrosis groups. Of the 356 patients, 146 (41%) presented with Grade 2 or higher levels of BMF. Extramedullary disease was detected in 52 patients (14.6%), while 54 patients (15.2%) had paraskeletal plasmacytoma. Grade 2 or 3 BMF was observed in 40 of the 52 patients with extramedullary disease (p < 0.01). Consistently, in the 210 patients without BMF, EMD was absent in 198 cases (p < 0.01). In multivariable logistic regression analysis, BMF status (OR = 3.200, 95% CI: 1.010-10.141, p = 0.048) and elevated serum lactate dehydrogenase (LDH) levels (OR = 1.003, 95% CI: 1.000-1.005, p = 0.037) were identified as independent predictors of synchronous extramedullary disease. In conclusion, our study indicates that increased BMF in patients with multiple myeloma is closely associated with synchronous extramedullary dissemination. Consequently, evaluating BMF at initial diagnosis may serve as a useful surrogate marker to identify patients presenting with concurrent extramedullary involvement.
BACKGROUND:Higher von Willebrand factor (VWF) levels and lower ADAMTS13 activity are linked to increased risk of atherosclerotic cardiovascular disease, but their association with atherosclerosis burden, a potential underlying mechanism, remains unclear. We investigated associations of these biomarkers with arterial calcification, a surrogate of atherosclerosis, in a general population. METHODS:In 2224 Rotterdam Study participants with measured VWF Antigen level (VWF:Ag) and ADAMTS13 activity (in percentage), computed tomography assessed calcification volume in the coronary arteries (CAC), aortic arch (AAC), and extracranial and intracranial carotid arteries (ECAC, ICAC) (mean age 69.5 ± 6.7 years; 51.5% female). Associations of VWF:Ag, ADAMTS13 activity, and their ratio (linear and quartiles) with calcification (linear and quartiles) were evaluated using multivariable linear and proportional odds logistic regression, adjusting for demographic and cardiovascular factors. RESULTS:Higher ADAMTS13 activity was significantly associated with lower volume of CAC (β [95% CI]: -0.04 [-0.08, -0.01]), AAC (-0.08 [-0.11, -0.03]), and ECAC (-0.05 [-0.09, -0.01]), but not in ICAC. A higher ADAMTS13:VWF ratio showed stronger inverse associations, extending to ICAC, suggesting a potential interplay between ADAMTS13 and VWF (β [95% CI]: CAC: -0.12 [-0.21, -0.02]; AAC: -0.20 [-0.30, -0.10]; ECAC: -0.08 [-0.18, -0.01]; ICAC: -0.11 [-0.21, -0.02]). The effect size of the ratio increased across quartiles at all artery-specific locations, strengthening the observed relationship. Across levels of calcification, associations of the biomarkers remained generally unchanged. CONCLUSIONS:Our findings support the potential relevance of ADAMTS13 activity in arterial calcification and, by extension, atherosclerosis. The observed associations may reflect both its balance with VWF and pathways independent of VWF. Future longitudinal and causal studies should determine whether ADAMTS13 influences the development and progression of arterial calcification through VWF-dependent or VWF-independent pathways, thereby clarifying its biological role and potentially identifying targets for preventive strategies against atherosclerotic vascular disease.
This retrospective, single-center study aimed to characterize clonal dynamics of GPI-deficient cells in patients with paroxysmal nocturnal hemoglobinuria (PNH) or PNH/aplastic anemia (AA) syndrome using multiparameter flow cytometry including FLAER. Among 108 patients diagnosed and treated at our center, 83 had longitudinal monitoring of GPI-deficient neutrophils; 53 of these also had data on monocytes and lymphocytes. Median observation time was 29.4 months (range 1.1-162.7 months). Clone size in neutrophils showed a strong correlation with monocytes, but not with lymphocytes. Clonal persistence represented the most frequent individual pattern of clone evolution observed during follow-up; clonal persistence was observed in 32/83 patients, while 24 patients exhibited clonal expansion (≥ 10%) and 13 showed regression. Expansion frequently involved all three lineages, suggesting ongoing biological mechanisms contributing to clonal selection. Regression was more likely in patients with small initial clones. In six patients undergoing allogeneic stem cell transplantation, complete eradication of PNH clones was achieved. Clonal dynamics were independent of eculizumab treatment; however, regression was observed in some patients treated with ATG and cyclosporine A. These findings support the need for longitudinal clone size monitoring, particularly in neutrophils and monocytes. Further studies are warranted to elucidate factors influencing clone expansion and remission. Trial Registration: 25-12 634-BO.
BACKGROUND:Long-term treatment with Bruton's tyrosine kinase inhibitors has substantially improved outcomes in chronic lymphocytic leukemia (CLL). However, real-world evidence simultaneously evaluating clinical outcomes, treatment adherence, persistence, and adverse event management remains limited. This study assessed long-term treatment dynamics and clinical outcomes in patients with CLL receiving ibrutinib in routine clinical practice. METHODS:We conducted a multicenter, retrospective, observational study involving four Italian centers. Adult patients with CLL treated with ibrutinib between January 2016 and June 2024 were included. Clinical records were linked with hospital pharmacy dispensing registries to evaluate progression-free survival (PFS), overall survival (OS), time to treatment discontinuation (TTD), adherence, persistence, and adverse event management. Adherence was calculated using dispensing data adjusted according to the prescribed daily dose (PDD). Kaplan-Meier analyses were performed for survival outcomes, while multivariable logistic and Cox regression models were used to identify factors associated with adherence and clinical outcomes. RESULTS:A total of 276 patients were included (47% first-line, 36% second-line, and 17% third-line or later therapy). Mean age was 70 ± 10 years and 63% were male. Adherence remained consistently high across treatment lines and throughout follow-up, with mean adherence values generally ranging between 0.75 and 0.90. At 8 years, first-line patients achieved PFS, OS, and TTD rates of 86.4%, 64.5%, and 61.4%, respectively. Corresponding estimates were 72.7%, 49.5%, and 23.1% in second-line patients and 95.8%, 49.4%, and 53.5% among patients receiving third-line or later therapy. Adverse drug reactions occurred in 53% of patients; 74% resolved following clinical management. Higher comorbidity burden (CIRS > 6) was independently associated with optimal adherence (OR 2.12, 95% CI 1.12-4.00; p = 0.016) and lower risk of treatment discontinuation (HR 0.36, 95% CI 0.16-0.80; p = 0.013). CONCLUSIONS:Long-term treatment with ibrutinib was associated with favorable clinical outcomes, sustained adherence, and prolonged treatment persistence in routine clinical practice. Proactive adverse event management and individualized treatment optimization may contribute substantially to maintaining long-term treatment exposure and maximizing clinical benefit.
Despite disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) sharing features of thrombocytopenia, organ dysfunction, and bleeding, the relationship between these two conditions remains unclear. We therefore conducted a post hoc analysis of post-marketing surveillance data from Japan to evaluate the clinical characteristics of 2362 patients with DIC (TMA-like phenotype DIC, n = 217; and non-TMA-like phenotype DIC, n = 2145) who received thrombomodulin alfa (TM-α). TMA-like phenotype DIC was defined as platelet count < 15 × 104/μL, hemoglobin < 10 g/dL and lactate dehydrogenase > 500 IU/L. Approximately 9% of the registered infection-associated cases of DIC were TMA-like phenotype DIC. Patients with TMA-like phenotype were younger and had more renal dysfunction and liver dysfunction than those with non-TMA-like phenotype. Regarding the hemostatic examinations, fibrin/fibrinogen degradation products, D-dimer, and thrombin-antithrombin complex levels were higher in patients with TMA-like phenotype than in those with non-TMA-like phenotype. Patients with TMA-like phenotype had worse resolution of DIC and 28-day survival rates than those with non-TMA-like phenotype; however, the coagulation and fibrinolysis parameters in both groups showed improvement after TM-α administration. These findings describe a clinically severe subgroup of infection-associated DIC and should be interpreted as exploratory given that confirmatory TMA testing was unavailable.
BACKGROUND:The treatment landscape for chronic lymphocytic leukaemia (CLL) has transformed over the past decade. This study aimed to estimate the healthcare costs and health burden associated with CLL in Australia. METHODS:A Markov model was developed to simulate the lifetime healthcare costs and health outcomes associated with CLL in Australia under the CIT-only era and the current era incorporating targeted therapies. The model considered treatment initiation, switching, and long-term survival. Clinical inputs were derived from Australian Cancer Database data (2009-2020) for the CIT era, while cost and utility parameters were obtained from government sources and published literature. The model ran over a 15-year horizon, reflecting the average age of CLL onset in Australia (68 years). Deterministic and probabilistic sensitivity analyses were performed. RESULTS:Total healthcare costs were substantially higher in the targeted therapy era ($751 727 per patient) compared to the CIT era ($33 505 per patient). Drug costs, particularly continuous BTKis therapy, were the main driver ($739 960 vs. $15 359). CLL patients were estimated to accumulate 3.62 and 7.83 QALYs in the CIT and targeted therapy eras, respectively, compared to 10.56 QALYs for the general population aged 68-indicating QALY losses of 6.94 and 2.73, respectively. Life expectancy shortfalls were 6.69 and 3.21 years, respectively. Targeted therapy led to incremental gains of 4.22 QALYs and 3.47 life years. Sensitivity analysis identified that discount rate, age at onset, treatment costs, and time horizon significantly influenced incremental costs, while treatment effectiveness and quality of life in the progression-free state were key drivers of QALY gains. CONCLUSIONS:CLL imposes a significant economic burden and QALY loss. While targeted therapies offer meaningful health gains, their high cost highlights the need for strategic planning to ensure sustainable resource allocation. Policymakers should balance clinical benefit with financial impact to optimise value in cancer care.
