Long-term health-related quality of life and mental health in patients with immune thrombotic thrombocytopenic purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially life-threatening disorder. Treatment advances have lowered morbidity rates, but past acute events can still cause long-term consequences, reducing health-related quality of life (HRQoL) and determining cognitive impairment, anxiety, and depression. We aimed to investigate these aspects and the role of caplacizumab and rituximab: 39 patients were evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the FACIT-Fatigue, the Hospital Anxiety and Depression Scale, and the Functional Assessment in Cancer Therapy-Cognitive Function questionnaires. The median age at study inclusion was 50 years (IQR 38-60), and the median follow-up from diagnosis was 97 months (IQR 14-182); 82% of patients were female, and 36% had one or more recurrences. Caplacizumab was administered in 16 patients (41%), as well as rituximab. ITTP patients reported lower physical and mental HRQoL scores than the general population. No differences in physical or mental domains were observed between patients treated or not with caplacizumab, while those who received rituximab reported lower scores in mental health. Neurological impairment at diagnosis correlated with worse fatigue. The majority of patients (72%) reported anxiety or depression (82%). ITTP had a significant impact on the long-term cognitive function, fatigue, depression, and anxiety levels of patients, with a negative effect on their HRQoL. Our findings underscore the need to pay special attention to patients' long-term physical and mental health, regardless of the medical treatments received.

The new Systematic Coronary Risk Evaluation (SCORE2 and SCORE2-OP) estimates the risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib or ponatinib.

Patients with chronic myeloid leukemia (CML) treated with nilotinib or ponatinib may experience arterial occlusive events (AOEs). It is currently recommended to thoroughly assess cardiovascular risk factors before treating CML. We identified 455 consecutive CML adult patients, 335 treated with nilotinib and 120 with ponatinib; 380 patients without previous cardiovascular diseases or diabetes were stratified according to the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Older Persons (SCORE2-OP). This updated algorithm from the European Society of Cardiology (ESC) estimates a 10-year risk of fatal and non-fatal cardiovascular diseases. It is based on sex, age, smoking habits, systolic blood pressure, non-high-density lipoprotein cholesterol, and European geographical region of cardiovascular risk. The SCORE2/SCORE2-OP algorithm translated more patients (50.2%) to the high-very high cardiovascular risk category than the previous SCORE (25.3%). Patients with a high to very high SCORE2/SCORE2-OP risk showed a significantly higher incidence rate of AOEs (69.2% vs. 46.5%, p < 0.001). The older SCORE was less specific in estimating AOEs in patients classified as low-intermediate risk (69.8 vs. 54.2%). In multivariate analysis, no associations were found between AOEs and gender, age, and type or dose of tyrosine kinase inhibitor. Only the SCORE2/SCORE2-OP risk was confirmed as a significant predictive factor (p = 0.028; hazard ratio = 2.2; 95% confidence interval = 1.1-4.5). Patients with AOEs required, in most cases, imaging diagnostic tests, additional drugs, and sometimes invasive procedures, increasing access to visits and hospital management. This real-life study suggested that the SCORE2 and SCORE2-OP charts could help identify cardiovascular fragility in CML patients providing them with more attention and a proper TKI selection.

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML.

BACKGROUND: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. METHODS: A total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. RESULTS: Second-generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications. CONCLUSIONS: This observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use.

Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension.

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08-3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928-6.451, p < 0.001 and HR = 1.8; 95%CI 0.983-3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92-10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21-0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24-1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07-1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.

Systematic Review and Meta-Analysis of Health-Related Quality of Life in Patients with ß-Thalassemia that Underwent Hematopoietic Stem Cell Transplantation.

Background: ß-Thalassemia major (ß-TM) represents one of the most important hemoglobinopathies worldwide. Remarkable improvements have been achieved in supportive therapy based on blood transfusions and iron chelation, and nowadays, this approach is capable of assuring a long life in these patients in industrialized countries. The only curative treatment is represented by hematopoietic stem cell transplantation (HSCT). However, this treatment may be burdened by deterioration in the Health-Related Quality of Life (HRQoL). This paper aimed to evaluate the role of HRQoL in transplanted ß-TM patients with a systematic review and meta-analysis. Methods: PubMed database, Web of Science, and Scopus were systematically searched for studies published between January 1st, 2000 to September 2020. The following terms were entered in the database queries: ß-thalassemia, HRQoL, and HSCT. The study was carried out according to the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) statement. Results: We identified a total of 33 potential studies. Among these, 10 were finally considered in the systematic review and 5 in the meta-analysis. Overall, good scores in the principal domains of HRQoL were reported by transplanted patients. These data were confirmed by results of meta-analysis that showed significant difference between transplanted and ß-TM patients treated with conventional therapy in the physical and emotional dimension, with a medium effect size [d=0.65, 95% CI (0.29-1.02), z = 3.52, p =0.0004, I2=75%; and d=0.59, 95% CI (0.43-0.76), z = 6.99, p <0.00001, I2=0%, respectively]. Conclusion: HRQoL is generally good in ß-TM transplanted patients and may significantly contribute in deciding whether or not to transplant a ß-TM patient treated with conventional therapy.

Understanding the User's Point of View: When the Doctor Gets Sick with Cancer and Seeks Help.

Background: When physicians confront a serious personal illness, they may discover that the transition to the "sick" role is challenging and not easy. We conducted a qualitative study in which a group of doctors with cancer (DP) was compared with a group of patients with cancer, not doctors (NDP) but with a degree of education, qualifications, and a professional role comparable to that of a doctor. Objectives: The main objective was to evaluate the effect of the diagnosis and the treatment of cancer on both the patient's personal and professional life. It was also designed to understand the effect that the experience of cancer may have on the subsequent clinical practice of DP. Methods: The eligibility criteria included diagnosis of tumors of different sites and at any stage of disease treated with local (surgery, radiotherapy) or systemic (chemotherapy, hormonal, target) therapies or a combination of both; patients actively working. A semi-structured interview was used to collect information about the patient's cancer experiences. In both groups, six main themes and ten subthemes were identified. Results: From July to November 2021, 59 patients were enrolled in the study. Among them, 29 were DP and 30 were NDP. The median age and gender were 55.9 years ± 9.3 SD (range 38-82 y), M/F ratio 12/17 for DP, and 56.3 years ± 8.9 SD (range 40-83 y), M/F ratio 11/19 for NDP, respectively. The main themes were: theme 1, practical aspects related to diagnosis: most of the DP did not encounter difficulties in performing the tests necessary to confirm the diagnosis of cancer, unlike what was observed in NDP. Theme 2, cancer diagnosis experience: Many DP and NDP felt prepared for their own cancer experience. Two-thirds of DP already knew their cancer prognosis from their previous background knowledge and one-third of NDP did not want to discuss the prognosis in depth with their referring oncologists for the fear of learning that their cancer had a poor prognosis. Theme 3, treatment experience: for many DP, having a professional background contributed to more active participation in care and also in the management of side effects of treatments. Most NDP were satisfied with the treatment received in the hospital and the relationship with the health professionals. Theme 4, changes in work: None of the patients from both the groups stopped working permanently or lost their job because of the disease. A higher number of DP and NDP reported a loss of interest in their job. Theme 5, changes in personal/family life and friendships: more than half of the patients in both groups developed a new perspective on their private lives. Theme 6, comfort from faith: most of the patients in both groups who followed a faith, found comfort in that faith. For DP only, we explored the theme of the change in the doctor/patient relationship. Important findings from our study included positive changes in the doctor's clinical practice including having a more empathic relationship with patients, greater consideration of the psychological impact of cancer, and greater attention to certain symptoms of cancer reported by patients. Conclusion: This study suggests the need to know the special needs of professional patients, in particular, related to the emotional difficulties, maintenance of privacy, and the need for support on their return to work. These results can help to foster improvements in current cancer care practices.

Health-related quality of life profile of patients with immune thrombocytopenia in the real life is impaired by splenectomy.

The impact of splenectomy on health-related quality of life (HRQoL) in patients with immune thrombocytopenia (ITP) remains scarcely explored. Therefore, we evaluated HRQoL with the 36-Item Short-Form Health Survey (SF-36) in an internal cohort of 69 chronic ITP patients, overall and by type of treatment. Of these patients, 26 patients were splenectomized, while other patients were treated medically with thrombopoietin-receptor agonists (TPO-RAs) or immunosuppressive treatment. We also compared HRQoL of the splenectomized patients (internal cohort) with an external cohort of 63 splenectomized ITP patients and the general population. The median follow-up was 10 years (range 1-20). Splenectomized patients had a worse overall HRQoL profile than those who received medical therapy either with TPO-RAs or other treatments (OT), with clinically meaningful differences registered in several domains. These included physical functioning (Δ = - 17.0 and Δ = - 15.2, for TPO-Ras and OT, respectively, p = 0.065), role physical (Δ = - 9.7 and Δ = - 13.8, p = 0.483), and bodily pain (Δ = - 14.2 and Δ = - 18.8, p = 0.053). Compared to the general population, both internal and external splenectomized cohorts had an impaired HRQoL profile. Further studies on HRQoL in splenectomized ITP patients are needed to better understand the long-term impact of this surgical procedure.

Low-density lipoprotein (LDL) levels and risk of arterial occlusive events in chronic myeloid leukemia patients treated with nilotinib.

Recommendations for dyslipidemia management aimed at reducing arterial occlusive events (AOEs) have been recently published. So far, no data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib. We investigated 369 CML adult patients, stratified according to the new Systematic Coronary Risk Evaluation (SCORE) scoring system. Plasma levels of cholesterol, HDL, LDL, and triglycerides were measured prior to the start of nilotinib and after 3, 6, and 12 months. The 5-year cumulative incidence of AOEs was 15.9%. Patients with cholesterol levels > 200 mg/dL and LDL > 70 mg/dL 3 months after treatment showed a significantly higher incidence of AOEs (21.9 ± 4.6% vs 6.2 ± 2.5, P = 0.003). Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (34.4 ± 6% vs 10 ± 2.1%, P < 0.001). In multivariate analysis, both high cholesterol and LDL levels and a high and very high SCORE risk remained significantly associated with the risk of AOEs (P = 0.008; HR = 3.5; 95% CI = 1.4-8.7 and P < 0.001; HR = 4.4; 95% CI = 2-9.8, respectively). Overall, 78 patients (21.1%) presented dyslipidemia at the time of CML diagnosis and 88 (23.3%) after starting nilotinib, but only 26 of them (29.5%) were treated with statins.Low LDL and cholesterol plasma levels are associated with a significant lower risk of AOEs in CML patients treated with nilotinib in the real life.

Rituximab Monotherapy or in Combination with Bendamustine Is Not Inferior to Rituximab-CHOP Regimen in the Treatment of Patients with Splenic Marginal Zone Lymphoma in the Real Life.

Splenic marginal zone lymphoma (SMZL) is a rare lymphoma belonging to the marginal zone lymphoproliferative disorders. Usually, SMZL occurs with indolent presentation and, when required, the standard of care is represented by rituximab-based regimens. No direct comparison of different rituximab-based combinations and polychemotherapy regimens has been conducted to date. In a monocentric cohort of 68 SMLZ patients, we showed that rituximab in monotherapy or in combination with bendamustine, compared with rituximab associated with the polychemotherapy cycle cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), resulted in a higher 5-year progression-free survival (91.3 ± 9% and 75 ± 15.7% vs. 30.8 ± 12.1%, p < 0.001). Platelets at diagnosis <100 ×109/L (p = 0.034, HR = 4.3) and transformation into diffuse large B-cell lymphoma (p = 0.031, HR = 4.3) were associated with a lower overall survival.

Patient-Physician Communication in Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Introduction: An effective communication is an integral part of the patient-physician relationship. Lack of a healthy patient-physician relationship leads to a lower level of patient satisfaction, scarce understanding of interventions and poor adherence to treatment regimes. Patients need to be involved in the therapeutic process and the assessment of risks and perspectives of the illness in order to better evaluate their options. Physicians, in turn, must convey and communicate information clearly in order to avoid misunderstandings and consequently poor medical care. The patient-physician relationship in cancer care is extremely delicate due to the complexity of the disease. In cancer diagnosis, the physician must adopt a communicative approach that considers the psychosocial factors, needs and patient's preferences for information,which in turn all contribute to affect clinical outcomes. Search Strategy and Methods: This review was conducted using the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) statement. We included studies on the importance of physician-patient communication in Acute Myeloid Leukaemia and Myelodysplastic Syndrome care. We searched PubMed, Web of Sciences, Scopus, Google scholar for studies published from December 1 st , 2020 up to March 1 st , 2021. Using MeSH headings, we search for the terms "Physician and patient communication AND Acute Myeloid leukemia" or "Myelodysplastic syndrome" or "Doctor" or "Clinician", as well as variations thereof . Purpose of the Review: This review examines the progress in communication research between patient and physician and focuses on the impact of communication styles on patient-physician relationshipin hematologic cancers, including Acute Myeloid Leukaemia and Myelodysplastic Syndromes.

Health-Related Quality of Life Assessment in Patients with Myelodysplastic Syndromes: Evidence from Randomized Clinical Trials.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and blood cytopenia with a variable risk of progression to acute myeloid leukemia. The main goal of therapy for the large majority of patients is to improve health-related quality of life (HRQoL). Its rigorous assessment is now recommended in international MDS guidelines. Our review provides an overview of HRQoL results from randomized controlled trials (RCTs) in MDS patients. The literature search undertaken in PubMed identified 10 RCTs with HRQoL endpoints (all secondary) published between August 2008 and September 2020. These RCTs have helped to better understand the impact of therapies from the patient perspective and have generated valuable information that can be used to further support clinical decisions. However, the number of RCTs in MDS patients, including HRQoL endpoints, is still low. Given the importance of symptom relief and HRQoL improvement in the treatment of MDS patients, the assessment of the patient perspective in future RCTs is highly recommended to keep expanding the knowledge of the impact of new MDS therapies.

Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors.

Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rdG TKIs.

Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart.

Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 60-month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28 months (range, 3-69 months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P < 0.001). Patients aged ≥60 years showed a significantly higher incidence rate of AOEs (51.5% vs 16.9%, P = 0.008). In multivariate analysis, no association was found between AOEs and positive history of CV disease, age, dose of ponatinib, previous exposure to nilotinib, and comorbidities. Only the SCORE risk was confirmed as a significant predictive factor (P = 0.01; HR = 10.9; 95% C.I. = 1.7-67.8). Patients aged ≥60 years who were treated with aspirin had a lower incidence rate of AOEs (33.3% vs 61.8%). Among the 14 reported AOEs, 78.6% of them showed grade 3 to 4 toxicity. This real-life study confirmed the increased incidence of AOEs in CML patients treated with ponatinib, with high to very high SCORE risk. We suggest that patients aged ≥60 years who were treated with ponatinib should undergo prophylaxis with 100 mg/day of aspirin. Our findings emphasize personalized prevention strategies based on CV risk factors.

Incidence and evaluation of predisposition to cardiovascular toxicity in chronic myeloid leukemia patients treated with bosutinib in the real-life practice.

There is little information about cardiovascular adverse event (CV-AE) incidence in chronic myeloid leukemia (CML) patients treated with bosutinib in the real-life practice. We identified 54 consecutive CML patients treated with bosutinib, stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 40-month cumulative incidence of CV-AEs was 25.2 ± 8.1%. Patients with the SCORE of high-very high showed a significantly higher incidence of CV-AEs (55 ± 12.9% vs 9 ± 9.5%; p = 0.002). Overall, 9 CV-AEs were reported, with 2 deaths attributed to CV-AE. In conclusion, the SCORE assessment before starting treatment is helpful in identifying CV-AE high-risk patients during bosutinib treatment.

Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia.

BACKGROUND: While the outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients. METHODS: We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients. RESULTS: The median age at diagnosis was 80 years (range: 75-96). In the first line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third line, and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In the first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e., 3-month BCR::ABL1IS < 10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, respectively, with 16.6%, 35.7%, and 51.7% achieving a deep molecular response (DMR) at the same time points. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade ≥ 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (p = 0.033). Overall, the median follow-up was 46.62 months (range: 1.8-206.2), and 43 patients died due to non-CML-related causes. Three patients died due to disease progression to advanced (n = 1) and blastic (n = 2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63-0.81), with no significant difference between the patients treated with standard doses of TKIs compared to those treated with reduced doses (p = 0.35). CONCLUSIONS: TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.

Extracellular vesicles in the Chronic Myeloid Leukemia scenario: an update about the shuttling of disease markers and therapeutic molecules.

Extracellular vesicles (EVs) are various sets of cell-derived membranous structures containing lipids, nucleic acids, and proteins secreted by both eukaryotic and prokaryotic cells. It is now well recognized that EVs are key intercellular communication mediators, allowing the functional transfer of bioactive chemicals from one cell to another in both healthy and pathological pathways. It is evident that the condition of the producer cells heavily influences the composition of EVs. Hence, phenotypic changes in the parent cells are mirrored in the design of the secreted EVs. As a result, EVs have been investigated for a wide range of medicinal and diagnostic uses in different hematological diseases. EVs have only recently been studied in the context of Chronic Myeloid Leukemia (CML), a blood malignancy defined by the chromosomal rearrangement t(9;22) and the fusion gene BCR-ABL1. The findings range from the impact on pathogenesis to the possible use of EVs as medicinal chemical carriers. This review aims to provide for the first time an update on our understanding of EVs as carriers of CML biomarkers for minimal residual disease monitoring, therapy response, and its management, as well as the limited reports on the use of EVs as therapeutic shuttles for innovative treatment approaches.