Asciminib represents a significant advancement in the treatment of chronic myeloid leukemia, establishing a novel therapeutic paradigm by specifically targeting the ABL1 myristoyl pocket, a mechanism distinct from that of conventional adenosine triphosphate-competitive inhibitors. Such a selective inhibitor offers an alternative treatment strategy for patients with chronic myeloid leukemia who have developed resistance to previous tyrosine kinase inhibitor therapies. Although asciminib demonstrates a superior safety profile, primarily characterized by a reduction in cardiovascular adverse events associated with prior tyrosine kinase inhibitors, its clinical significance extends further. The effectiveness of asciminib, combined with its capacity to overcome resistance through combination strategies with adenosine triphosphate-binding site tyrosine kinase inhibitors, establishes it as a focal point in emerging chronic myeloid leukemia treatment approaches. It remains essential to continue research and clinical trials to enhance the therapeutic efficacy of asciminib and manage its associated side effects.

Chronic myeloid leukemia (CML) was the first leukemia to be described in medical literature and remains one of the most well-studied hematologic malignancies. This review traces the historical evolution of CML research, from its first clinical recognition in the mid-19th century to modern molecular diagnostics and targeted therapy. Key milestones include the discovery of the Philadelphia chromosome in 1960, identification of the BCR::ABL1 fusion gene in the 1980s, and the subsequent development of tyrosine kinase inhibitors (TKIs). The introduction of imatinib in the early 2000s revolutionized CML treatment, transforming a fatal disease into a chronic condition with near-normal life expectancy for most patients. Second- and third-generation TKIs have since been introduced to overcome drug resistance and target specific BCR::ABL1 mutations, such as T315I. Recently, research has focused on mechanisms of TKI resistance, novel signaling pathways, and strategies to achieve treatment-free remission (TFR). Emerging therapies such as vamotinib, KF1601, and combination regimens are being explored. Furthermore, new insights into non-kinase functions of BCR::ABL1 and the role of microRNAs in resistance open additional therapeutic avenues. This review provides a concise overview of CML from a historical and molecular perspective, highlighting diagnostic advances, evolving response criteria, and future directions in treatment.

Molecular findings have led to adeeper understanding of the pathophysiology of numerous diseases and now form the basis for targeted treatment. An example of this is chronic myeloid leukemia (CML). The identification of the BCR::ABL1 translocation enabled the development of specific tyrosine kinase inhibitors. While the median survival time used to be 4 years, CML is now often achronic disease with anear-normal life expectancy thanks to targeted treatment; however, most tumor diseases are more complex at the molecular level. Advances in genome analysis enable increasingly more refined molecular characterization. Common tumor diseases are thus divided into increasingly smaller molecularly distinct segments, which become rarer as individual entities but can also be treated in amore targeted and individualized manner. The concept of personalized medicine is manifested in molecular tumor boards. Asimilar approach can start from rare genetic syndromes. In this case, understanding the underlying pathophysiology does not necessarily lead to acausal treatment of the syndrome itself but it does enable new treatment options for frequent diseases. An example is thyroid hormone resistance (RTH)β. Findings on the effect of thyroid hormone receptorβ in the liver have contributed to the development of analogues that can now be used specifically to treat metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis and can possibly also have the potential to reduce the progression of liver cirrhosis. Overall, close cooperation between human genetics and internal medicine can substantially contribute to an improvement in treatment success. Abetter understanding of molecular disease mechanisms enables an increasingly more precise, individualized and effective treatment.

Targeted therapies have made near normal life span an attainable goal for many patients with chronic phase (CP) chronic myeloid leukemia (CML). Most patients require years of therapy and not everyone may be able to discontinue treatment permanently without CML recurrence. BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs) including ATP binding site and allosteric inhibitors that bind to the myristoyl pocket are associated with treatment-emergent adverse events (TEAEs) that may compromise quality of life and well-being. Although alternative treatment options exist, side effects may persist, or new ones occur after a therapy switch. Using a case-based approach, this review examines the incidence of non-hematologic and hematologic TEAEs with specific therapies, provides guidance on AE management, and describes the impact of therapy dose reduction on efficacy and tolerability.

As survival rates among patients with chronic myeloid leukemia (CML) have improved significantly, treatment goals have expanded from disease control to optimizing long-term quality of life (QoL). The multicenter cross-sectional study used relevant survey questionnaires to gather comprehensive data on baseline characteristics, clinical treatment, economic burdens, psychological status, adverse events (AEs), and QoL among patients with CML. In all, 2,035 valid questionnaires were included for analysis. Psychological burden assessments indicate a high prevalence of mental health symptoms: 38.5% of patients report experiencing anxiety symptoms, whereas 46% exhibit symptoms of depression. This study identified a high-burden group experiencing significant economic and psychological stressors, which are associated with poor clinical responses. Psychological burden is central to the psychosocial clinical network and exhibits the strongest correlation with QoL (r = 0.64). Notably, the mediation model indicates that psychological burden fully mediates the effect of economic burden on QoL (85.3%) and partially mediates its influence on medication adherence (35.5%). Furthermore, we identified a clinically significant subgroup characterized as QoL lag-patients who achieve deep molecular response but report low QoL. This discrepancy is independently predicted by multiple AEs (≥6 types: OR = 2.09), serious AEs (OR = 1.90), comorbidities (OR = 2.44), and escalating psychological burden (OR = 1.59). The findings underscore the need to shift the treatment of CML toward a holistic management paradigm. Clinical practice must actively engage with patients' concerns to optimize treatment efficacy, adjust drug dosages appropriately, and integrate social resources to provide psychological, economic, and familial support.

The modern management of chronic myeloid leukaemia (CML) identifies a new therapeutic goal of treatment-free remission (TFR). Half of CML patients in durable deep molecular response (DMR) (MR4 or better) can remain off tyrosine kinase inhibitors (TKIs) without experiencing loss of major molecular response. Despite a large number of TFR studies to date, there are no consistent predictors of successful TFR. We conducted a single-centre cohort study on 197 patients discontinuing TKIs in DMR ≥1 year and TKI therapy ≥3 years. After TKI discontinuation, 98 patients (49.7%) lost MR4; of these, 90 (91.8%; and 45.7% of the whole cohort) lost major molecular response (MMR or MR3) after a median of 3.8 months (1-93.3). The 2-year probability of TFR (pTFR) was 57.7%. In multivariable analysis, male sex, age at diagnosis >40 years, faster achievement of MR4 and longer duration of DMR were the only variables significantly associated with higher pTFR. Based on the multivariable analysis results, we built a TFR prognostic score (TPS) able to distinguish three groups with different 2-year pTFR: good (89.9%), intermediate (61.2%) and poor (18.4%) TFR probability (p < 0.0001). We validated the TPS on an independent cohort of 91 patients. We propose that the TPS could become a useful guide for CML clinicians.

Polycythaemic panmyelosis in chronic myeloid leukaemia

Although mild leukocytosis is common in pregnancy, markedly elevated counts warrant prompt evaluation to exclude pathological causes such as infections and leukaemia. Chronic myeloid leukaemia (CML) is a chronic myeloproliferative condition increasingly being seen in younger age groups.Here we report a woman in her early 30s with asymptomatic marked leukocytosis at term, subsequently diagnosed with CML. As she was near term, she was managed conservatively through delivery before initiation of definitive therapy postpartum. This case underscores the importance of baseline and serial leucocyte monitoring in pregnancy and highlights the unique therapeutic challenges of managing CML during pregnancy.

Chronic myeloid leukemia (CML) is driven by the Ph chromosome, but additional genetic abnormalities (AGAs) such as ASXL1 mutations and other cytogenetic alterations contribute to poor prognosis and reduced treatment response. SETD2 plays a critical role in DNA repair and chromatin integrity and its non genomic loss-of-function (LOF) has been linked to disease progression in CML. This study examines how SETD2 LOF impacts on CML pathogenesis and its potential as a biomarker for high-risk disease.To investigate the role of SETD2 LOF in CML, cellular models with SETD2 silencing or overexpression were compared using liquid chromatography-tandem mass spectrometry (LC-MS/MS), RNA sequencing (RNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq). Validation was performed by Western blotting (WB), immunofluorescence (IF), and co-immunoprecipitation (co-IP) in proper cell fractions. Additionally, SNP-array analysis provided genomic insights.Differential transcriptomic profiling revealed SETD2-dependent transcriptional regulation of genes involved in DNA repair (MSH2, MSH6) and metabolic homeostasis (PFKP, LDHA, PDK1) (FIGURE 1A). Differential interactome profiling by LC-MS/MS identified SETD2 interactions with proteins critically involved in mismatch repair (MSH2, MSH6), cell division (α-/β-tubulin), and glycolysis (PFKP, PFKFB3, PD, and LDHA). Notably, SETD2 was also found to interact with key kinases regulating proliferation and stress response, including ERK1/2 and p38 MAPK. Integration of SNP-array analysis after chronic cell exposure to DNA damaging agents with ChIP-seq of SETD2-dependent H3K36me3 deposition sites confirmed that SETD2 plays a direct role in promoting faithful DNA damage response, since breakpoints were enriched at sites where H3K36me3 was disrupted by SETD2 LOF.Notably, we uncovered a novel role for SETD2 LOF in rewiring cellular metabolism: SETD2 re-expression attenuated the glycolytic shift observed in SETD2-deficient cells, as evidenced by downregulation of glycolytic enzymes (FIGURE 1 B, C, D), mitochondrial oxidative phosphorylation and overexpression of IDH1 enzyme which regulates a key step in the TCA, produces NADPH and protects cells from reactive oxygen species, acting as an antioxidant. Finally, SETD2/H3K36me3 deficiency as assessed by WB in total leukocytes could be detected in pts with AGAs at diagnosis and could discriminate pts who subsequently achieved non-optimal vs optimal responses to IM.Our findings point to SETD2 LOF as a key cooperating event in CML, that may act since diagnosis to set the stage for TKI resistance and disease acceleration by:• sustaining BCR::ABL1-independent genomic instability that fuels the acquisition of AGAs• metabolic reprogramming towards glycolysisWhether SETD2 LOF may serve as a biomarker of high-risk disease at diagnosis is an intriguing hypothesis that we are currently exploring in a larger cohort of uniformly treated pts.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL1 fusion gene. Although tyrosine kinase inhibitors (TKI) have revolutionized disease management, leukemic stem cells (LSCs) persist, sustaining minimal residual disease and relapse. A subset expressing the CD26 membrane marker represents a population of proliferating LSCs detectable in bone marrow and peripheral blood. Parallelly, extracellular vesicles (EV) have emerged as promising circulating biomarkers, as they carry BCR::ABL1 transcripts protected within their lipidic membrane. However, the relationship between residual CD26+ LSCs and EV-associated BCR::ABL1 remains unclear. This study aimed to explore the correlation between circulating CD26+ LSCs and vesicular BCR::ABL1 transcripts as complementary indicators of residual disease activity in CML.Peripheral blood (PB) from 44 adult CML patients in at least major molecular response under TKI therapy was analyzed. Circulating CD26+ LSCs were quantified by multiparametric flow cytometry on the CD45+/CD34+/CD38- population using four-color staining. The extracellular vesicle-enriched secretome (EVES) was isolated from plasma and characterized by Western blot, colloidal nanoplasmonic assay, and atomic force microscopy. Vesicular BCR::ABL1 transcripts were quantified by digital PCR (dPCR) and compared with BCR::ABL1 levels in PB cells.EVES characterization confirmed vesicular particles expressing CD63 and FLOT-1 (Figure 1A), with minimal soluble protein contamination (Figure 1B) and typical spherical morphology (Figure 1C). The median number of circulating CD26+ LSCs was 0.00625 cells/μL (range 0-0.1565), with 32% of patients showing undetectable levels. Median EVES BCR::ABL1 was 0.230 copies/μL (range 0-0.790), with 14% undetectable (Figure 1D). No correlation was found between CD26⁺ cells or EVES BCR::ABL1 and molecular response, BCR::ABL1 IS%, or dPCR values in PB cells, nor with age or therapy duration (Figure 1E). A significant inverse correlation was observed between CD26+ LSC counts and vesicular BCR::ABL1 transcripts (r = –0.39, p = 0.0085), even stronger in deep molecular responders (r = –0.45, p = 0.0079) (Figure 1F). Patients in treatment-free remission showed higher CD26+ LSC counts, whereas EVES BCR::ABL1 tended to be higher in those under TKI treatment (Figure 1G).Circulating CD26+ LSCs and vesicle-associated BCR::ABL1 transcripts show an inverse relationship, reflecting complementary aspects of residual leukemic activity in CML. As CD26+ LSCs decline, vesicular BCR::ABL1 may increase, possibly indicating activation of alternative leukemic compartments or enhanced vesicular secretion. Combined monitoring of these cellular and vesicular biomarkers may improve detection of residual disease and provide new insights into CML biology. Larger studies are needed to validate these findings and define the biological and prognostic significance of BCR::ABL1-loaded vesicles.

Background: We previously demonstrated that CD26+ leukemia stem cells (LSCs) are detectable by flow cytometry in the peripheral blood (PB) of chronic myeloid leukemia (CML) patients (pts) at diagnosis, during tyrosine kinase inhibitor (TKI) therapy, and in treatment-free remission (TFR). However, prospective data on the dynamics of PB CD26+LSCs from diagnosis and their potential correlation with molecular response (MR) are lacking.Methods: We report final results of a prospective, multicenter Italian study enrolling newly diagnosed chronic phase (CP) CML. Pts were centrally monitored by flow cytometry to quantify PB CD26+LSCs from diagnosis up to 24 months (mos) of therapy.Results: 242 consecutive CP-CML pts were included (132 treated with imatinib, 72 with nilotinib, and 38 with dasatinib). The CD26+LSC count at diagnosis varied among pts, with a median of 7.14 cells/µl (IQR 2.18–33.26 cells/µl). During TKI, we observed a rapid and significant reduction of CD26+LSCs, with median values decreasing to 0.013 cells/µL (IQR 0–0.034), 0.011 cells/µL (IQR 0–0.031), and 0.007 cells/µL (IQR 0–0.025) at 3, 12, and 24 mos, respectively. No significant differences in LSC log-reduction were observed according to the type of TKI employed. CD26+LSCs were significantly higher in the high Sokal risk group compared to intermediate or low risk groups (22.65 cells/µL vs 5.60 cells/µL vs 6.16 cells/µL) (p=0.018). A significant association was found between low CD26+LSCs count at diagnosis and optimal MR (BCR::ABL1 &lt;10% at 3 mos and &lt;0.1% at 12 and 24 mos). Pts achieving optimal MR at 3 mos had a median CD26+LSCs at diagnosis of 6.21 cells/µl (IQR 1.79–31.50), whereas suboptimal responders had a median of 19.87 cells/µL (IQR 5.37–39.81) (p=0.03). Similarly, optimal responders at 12 and 24 mos had significantly lower median CD26+LSCs at diagnosis compared to suboptimal responders (5.50 vs. 16.87 cells/µL, p=0.004 and 6.05 vs. 20.52 cells/µl, p=0.009, respectively). Furthermore, pts who switched TKI for failure had higher baseline CD26+LSCs counts (median 14.59 cells/µl; IQR 3.76–46) than those who did not switch (median 5.82 cells/µl; IQR 2.35–26.70; p=0.034). Three tertiles of CD26+LSCs at diagnosis were defined (&lt;3.21, 3.21–19.21, and &gt;19.21 cells/µL), showing significant correlation with MR rates: at 3 mos, the incidence of BCR::ABL1 &lt;10% was 93.5% in the lowest tertile vs. 78.8% in the highest (p=0.027); at 12 mos, optimal response was 78.5% vs. 62.8% (p=0.015); at 24 mos, response rates were 90.8% vs. 77.9% (p=0.079).Conclusions: This prospective study demonstrated a rapid rate of reduction of CD26+LSCs during TKI, confirming their long-lasting persistence even at very low levels. For the first time, a correlation between the amount of CD26+LSCs at diagnosis and the response to TKI treatment was documented. Given these results, the bulk of CD26+LSCs at diagnosis could represent an easily and rapidly measurable, new prognostic tool for predicting TKI response.

Introduction: We already demonstrated that, in chronic myeloid leukemia (CML), the peripheral blood (PB) CD34⁺/CD38⁻/CD26⁺ cell population represents a “CML-specific” circulating leukemic stem cell (LSC) compartment that can be quantified by flow cytometry at diagnosis, during tyrosine kinase inhibitor (TKI) therapy, and in treatment-free remission (TFR). We hypothesize that the persistence of circulating CD26⁺ LSCs may be linked to their capacity to evade immune surveillance. One possible mechanism may involve the presence or absence of immune checkpoint molecules such as PD-L1 on LSCs, which can hamper an anti-leukemic T-cell response.Methods: PD-L1 expression was evaluated at diagnosis in a proportion of CML patients enrolled in the prospective multicenter Stem CML Cure study. CD34⁺/CD38⁻/CD26⁺ cells were identified by flow cytometry and incubated with an anti–PD-L1 antibody. For each sample, at least 1×10⁶ events were acquired and analyzed.Results: A total of 77 consecutive chronic-phase (CP) CML patients were enrolled. As expected, PB CD26⁺ LSCs were detectable at diagnosis in all cases, with a median value of 12.97 cells/µL (range 0.051–281.97 cells/µL), confirming the strong diagnostic potential of this rapid flow-cytometry assay. Regarding PD-L1 co-expression, 34% (26/77) of patients showed no detectable PD-L1 on CD26⁺ LSCs (Figure 1, A), whereas 66% (51/77) exhibited variable PD-L1 expression levels (positivity range: 12–82%; median: 28%) (Figure 1, B-C, D). These findings highlight interpatient heterogeneity in the “immune-interactive” phenotype of CD26⁺ LSCs. We then correlated PD-L1 expression at diagnosis with the molecular response obtained at 24 months of TKI treatment in the first 35/77 (45%) CML patients. We documented an optimal response (BCR::ABL1&lt; 0.1%) in 25/35 (71,5%) patients and a suboptimal response (BCR::ABL1 &gt;0.1%) in 10/35 (28,5%) patients. Among the latter, PD-L1 expression on CD26⁺ LSCs was detected in 6/10 (60%) cases.Conclusions: These preliminary results suggest that CD26⁺/PD-L1⁺ LSCs may evade immune checkpoint controls, potentially contributing to the persistence of circulating LSCs with the consequent possibility of disease relapse even years after TKI discontinuation. Future analyses of patients attempting TKI cessation within this ongoing study will clarify whether differential PD-L1 expression on CD26⁺ LSCs influences the ability to achieve and sustain stable TFR.

Introduction: Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML) patients, though resistance remains a challenge. Emerging evidence suggests that chronic inflammation and epigenetic reprogramming contribute to disease progression and immune evasion. Genes involved in immune modulation, epigenetic regulation and immune checkpoint control are gaining interest in this context.Aim: This study aimed to: 1) evaluate the expression of ROCK2, IGFBP6, BMI1, EZH2, and PD-L1 in 21 CML patients at diagnosis and after 12 months of treatment; 2) explore correlations among these genes; and 3) assess whether PD-L1 polymorphisms [rs2282055 (T&gt;G), rs4143815 (G&gt;C), rs10815225 (G&gt;C)] affect PD-L1 expression or show clinical relevance.Methods: Gene expression was assessed using a novel multiplex droplet digital PCR (ddPCR) method, allowing simultaneous quantification of the target genes and GAPDH as a reference. PD-L1 genotyping was performed via RT-PCR using a commercial kit.Results: Median patient age was 54 years (range: 21–83); 11 had low ELTS risk, 4 high risk. Eleven patients were treated with imatinib, ten with nilotinib. After a median follow-up of 40 months, the 3-year event-free survival (EFS) rate was 75%. At 12 months, 60% of patients achieved MR3 or DMR (37% on imatinib vs 81% on nilotinib). EFS was not linked to ELTS risk but was influenced by comorbidities. Elevated inflammatory status (SIRI) correlated with worse EFS (3y-EFS: 90% low vs 62% high SIRI), though not statistically significant.Lower baseline EZH2 expression was significantly associated with prolonged EFS (90% vs 45%) and correlated with BMI1, IGFBP6, and PD-L1 levels. Lower EZH2 and BMI1 expression at 12 months was associated with deeper molecular response. ROCK2 and PD-L1 expression increased at 12 months, while IGFBP6 remained stable. No significant correlation was observed between PD-L1 polymorphisms and expression levels.Conclusions: In conclusion, this study highlights a correlation between BMI1 and EZH2 expression, consistent with mechanisms seen in solid tumors, where EZH2 promotes BMI1 via miR-200c deregulation. It also supports a functional link between ROCK2 and PD-L1, aligning with the work of Meng et al. (2020), who demonstrated a ROCK-dependent mechanism regulating PD-L1 stability via moesin phosphorylation in cancer cells. A similar regulatory mechanism may exist in CML, offering new therapeutic insights.

IntroductionThe advent of tyrosine kinase inhibitors (TKI) has revolutionised the treatment of chronic myeloid leukaemia (CML). Nevertheless, no specific tools are currently available to support follow-up and guarantee the adequate management of safety, adherence, and effectiveness altogether of TKI-based regimens. This study aimed to introduce a monitoring instrument tailored to patients undergoing TKI therapy for CML.Data SourceA structured instrument proposal was developed after conducting an integrative review. The instrument was then evaluated by clinicians and laboratory professionals with expertise in onco-haematology, who assessed clarity, objectivity, practicality, and clinical relevance using a five-point Likert scale.Data SummaryThe model comprised three protocols designed to evaluate adherence, safety, and effectiveness of TKI therapy. During evaluation of the instrument, all assessed parameters achieved mean scores ≥ 3.0. By aligning with international guidelines, the instrument consolidates essential monitoring parameters, thereby enhancing clinical decision-making and supporting patient-centred care in CML.ConclusionInstruments of this nature are rare and represent an important challenge for healthcare teams managing CML patients. Considering that adherence and safety are critical determinants of therapeutic success, structured tools such as this have the potential to facilitate improved outcomes.

The goal of the "Spot On CML" program is to provide diagnostic and monitoring tests to chronic myeloid leukemia (CML) patients in low- and middle-income countries (LMICs). Previously, we demonstrated reproducible BCR::ABL1 transcript quantification using dried blood spots (DBS). We have now optimized methods of DNA and RNA extraction from DBS, allowing the detection of myeloid gene variants, including ABL1 tyrosine kinase domain mutations. Among 177 CML patients from nine countries, ABL1 mutations were identified in 61 (34%) patients, with multiple mutations present in some cases. The most common ABL1 mutation was T315I (45.9% of patients with ABL1 mutations). Among 69 patients, 89 Tier I-II variants (pathogenic or likely pathogenic) were identified in other genes, including 52 ASXL1 variants in 49 patients. The detection of ASXL1 variants correlated strongly with the presence of ABL1 mutations (P = 3.51E-04). These methodologies are directly applicable to all assays used for the diagnosis, prognosis, and monitoring of CML and have important implications in bringing state-of-the-art genetic analysis to CML patients in LMICs.

Treatment-free remission (TFR) is an emerging goal for patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI). However, long-term TFR durability in real-world settings remains understudied. The J-SKI study, a large observational study, was conducted to evaluate long-term TFR outcomes in Japanese patients with CML. This interim analysis included 795 eligible patients from the prospective (n = 283) and retrospective (n = 512) cohorts. With a median follow-up of 32months (range 0.8-168) after TKI discontinuation, the 5-year TFR rate was 65.2% (95% confidence interval [CI]: 59.6-70.6%). Among patients who experienced molecular relapse, 99% (95% CI: 97-100%) regained a major molecular response after resuming TKI therapy, with no observed disease progression. Multivariate analysis identified the duration of deep molecular response (DMR) as the sole independent predictor of successful TFR, with each additional year of DMR reducing the relapse risk by 12.5% (HR: 0.875, p < 0.0001). A second TFR attempt was successful in 41% (95% CI: 22-59%) of the 32 patients. This study demonstrated that TKI discontinuation is a safe and feasible strategy in a real-world clinical setting. A sustained DMR is critical for TFR success, supporting its importance as a key therapeutic objective.

Hyperoside impairs mitochondrial respiration in chronic myeloid leukemia by promoting STUB1-mediated ubiquitination and degradation of NOX4.

Disparities in adherence to guideline-recommended cancer monitoring persist, with historically disadvantaged populations receiving less frequent testing. Although primary care physicians (PCPs) play a central role in long-term cancer care, and oncologists directly oversee treatment, the influence of shared identity with either clinician type on biomarker testing adherence remains underexplored. This study examines whether patient-physician concordance in race/ethnicity and gender-specifically with PCPs and oncologists-is associated with adherence to BCR::ABL1 testing in chronic myeloid leukemia (CML). We analyzed electronic health record data of 425 patients with CML diagnosed between 2007 and 2019, 385 PCPs, and 113 oncologists from an integrated health care system. We defined concordance by shared race/ethnicity, gender, and their combination between patients and each physician type. Biomarker testing adherence was measured as the proportion of guideline-recommended BCR::ABL1 tests completed annually. Linear mixed-effects models assessed associations, adjusting for demographic, clinical, socioeconomic, and care-seeking factors. Random intercepts for patients and physicians were included to account for individual baseline adherence levels and variability in practice patterns across both PCPs and oncologists. Over a 7-year follow-up, patient-PCP race/ethnicity and gender concordance was associated with a 4.8 percentage point (pp) increase in biomarker testing adherence in a given year (95% CI, 1.1-8.5; P=.012), with stronger effects among historically disadvantaged patients (6.6 pp; P=.03). Gender concordance alone showed a modest association (3.5 pp; P=.04). In contrast, no statistically significant associations were found for patient-oncologist concordance across any dimension (race/ethnicity: -1.4 pp; 95% CI, -5.8 to 2.9; P=.53; gender: 0.5 pp; 95% CI, -2.5 to 3.6; P=.73; combined race/ethnicity and gender: -1.1 pp; 95% CI, -6.2 to 3.9; P=.68). Shared identity with PCPs-but not oncologists-was associated with improved adherence to molecular monitoring guidelines in CML. In chronic cancer care within integrated health care systems, PCPs are well positioned to reinforce oncology-driven testing plans. These findings highlight the importance of fostering patient-centered relationships and promoting workforce diversity in primary care, particularly given that historically disadvantaged patients experienced the greatest gains in adherence.

Dasatinib, a second-generation tyrosine kinase inhibitor, is highly effective in chronic myeloid leukaemia (CML) but is associated with pleural complications in approximately 28%-37% of patients. We report four patients with CML who developed dasatinib-induced pleural effusion after prolonged treatment (2-10 years), including one case of chylothorax. All presented with dyspnea, and imaging with diagnostic thoracentesis confirmed exudative pleural effusions. One patient demonstrated triglyceride-rich fluid consistent with chylothorax. Dose reduction of dasatinib to 50 mg/day led to complete clinical and radiological resolution in three patients while maintaining molecular remission. The fourth patient encountered recurrent chylothorax despite dosage modification and supportive therapy, necessitating permanent discontinuation of dasatinib and transition to nilotinib, resulting in sustained radiological resolution and continued molecular response. This case series highlights the spectrum of late-onset dasatinib-related pleural complications and demonstrates that timely dose modification or TKI switching can effectively manage toxicity while preserving oncological outcomes.

A 52-year-old man with chronic myeloid leukaemia (CML) who had been receiving dasatinib 100 mg/day for 13 years presented with progressive dyspnea. Chest radiography revealed bilateral pleural effusions, and further evaluation confirmed the diagnosis of chylothorax. Dasatinib-induced chylothorax was suspected, and discontinuation of the drug led to clinical improvement. Dasatinib is a tyrosine kinase inhibitor (TKI) used for the treatment of CML and Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph + ALL). Although pleural effusion is a relatively common adverse effect, chylothorax is an extremely rare complication. This case highlights the importance of considering chylothorax as a potential cause of pleural effusion in patients undergoing long-term dasatinib therapy. In addition, based on the presumed pathophysiological mechanism, drug discontinuation appears to be the most crucial therapeutic approach for dasatinib-induced chylothorax.