A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia.

Ponatinib may be effective in chronic myeloid leukemia (CML) patients after failure of first/second line therapies. Although its efficacy for minimum plasma concentrations (C) is >21.3 ng/mL (equal to 40 nM), ponatinib may cause adverse events (AE) that require dose optimization.

Patient-reported symptom monitoring and adherence to therapy in patients with newly diagnosed chronic myeloid leukemia.

Background: The authors assessed the clinical utility of patient-reported symptom monitoring in the setting of newly diagnosed chronic myeloid leukemia (CML). The primary objective was to evaluate adherence to therapy.

Methods: The authors conducted an international prospective study that included patients with newly diagnosed, chronic-phase CML.

Impact on mental health, disease management, and socioeconomic modifications in hematological patients during the COVID-19 pandemic in Italy.

Background: Hematological patients are a highly vulnerable population with an increased risk of developing severe COVID-19 symptoms due to their immunocompromised status. COVID-19 has proven to cause serious mental health issues, such as stress, anxiety, and depression in the general population. However, data on the psycho-social impact of COVID-19 on hematological patients are lacking.

Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome.

CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting.

Clinical and Psychological Factors to Consider in Achieving Treatment-Free Remission in Patients With Chronic Myeloid Leukemia.

Treatment of chronic myeloid leukemia (CML) has evolved dramatically in recent years. In this regard, the introduction of second-generation tyrosine kinase inhibitors (TKI) has revolutionized therapeutic goals, and it is now desirable to obtain treatment-free remission (TFR), i.e.

Adherence, persistence and efficacy of dasatinib and nilotinib in the treatment of patients resistant or intolerant to imatinib with chronic myeloid leukemia in chronic phase: an Italian multicenter study over two years in real life.

Background: The use of dasatinib and nilotinib in the treatment of patients with chronic myeloid leukemia represents a valid therapeutic option for patients resistant or intolerant to imatinib. In this multicentre study, adherence, persistence and efficacy in real life over two years of treatment were evaluated.

Materials And Methods: Adherence to treatment was calculated as the ratio between the dose received and the prescribed dose.

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP.

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR).

The Q-LAMP Method Represents a Valid and Rapid Alternative for the Detection of the Rearrangement in Philadelphia-Positive Leukemias.

Molecular detection of the fusion transcripts is necessary for the genetic confirmation of a chronic myeloid leukemia diagnosis and for the risk classification of acute lymphoblastic leukemia. mRNAs are usually identified using a conventional RT-PCR technique according to the BIOMED-1 method. In this study, we evaluated 122 -positive samples with the Q-LAMP assay to establish if this technology may represent a valid alternative to the qualitative BIOMED-1 PCR technique usually employed for the detection and the discrimination of the common transcripts (p190 and p210 isoforms).

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.

Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia.

The introduction of second-generation tyrosine-kinase inhibitors (TKIs) has generated a lively debate on the choice of first-line TKI in chronic phase, chronic myeloid leukemia (CML). Despite the TKIs have different efficacy and toxicity profiles, the planned use of two TKIs has never been investigated. We report on a phase 2 study that was designed to evaluate efficacy and safety of a treatment alternating nilotinib and imatinib, in newly diagnosed BCR-ABL1 positive, chronic phase, CML patients.

Selective strong synergism of Ruxolitinib and second generation tyrosine kinase inhibitors to overcome bone marrow stroma related drug resistance in chronic myelogenous leukemia.

The IC50 of TKIs is significantly increased when BCR-ABL+ K562 cell line is cultured in stroma conditioned media produced by BM mesenchymal cells. In particular, while the Imatinib IC50 in the stromal co-cultures was well above the in vivo through levels of the drug, the IC50s of second generation TKIs were still below their through levels. Moreover, we provide a formal comparison of the synergy between first and second generation TKIs with the JAK inhibitor Ruxolitinib to overcome BM stroma related TKI resistance.

Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population.

The main objective of this study was to investigate whether patients with chronic myeloid leukemia (CML) in treatment with long-term therapy imatinib have a different health-related quality-of-life (HRQOL) profile compared with the general population. In total, 448 CML patients were enrolled, and the SF-36 Health Survey was used to compare generic HRQOL profiles. Symptoms were also assessed.

High-avidity cytotoxic T lymphocytes specific for a new PRAME-derived peptide can target leukemic and leukemic-precursor cells.

The cancer testis antigen (CTA) preferentially expressed antigen of melanoma (PRAME) is overexpressed by many hematologic malignancies, but is absent on normal tissues, including hematopoietic progenitor cells, and may therefore be an appropriate candidate for T cell-mediated immunotherapy. Because it is likely that an effective antitumor response will require high-avidity, PRAME-specific cytotoxic T lymphocytes (CTLs), we attempted to generate such CTLs using professional and artificial antigen-presenting cells loaded with a peptide library spanning the entire PRAME protein and consisting of 125 synthetic pentadecapeptides overlapping by 11 amino acids. We successfully generated polyclonal, PRAME-specific CTL lines and elicited high-avidity CTLs, with a high proportion of cells recognizing a previously uninvestigated HLA-A*02-restricted epitope, P435-9mer (NLTHVLYPV).

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.

A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61).

Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia.

The cancer testis antigen (CTA) preferentially expressed antigen of melanoma (PRAME) is overexpressed in many hematologic malignancies, including chronic myeloid leukemia (CML). The sensitivity of CML to donor lymphocyte infusion after allogeneic stem cell transplantation suggests this tumor can be highly susceptible to cellular immunotherapy targeted to tumor associated antigens. We therefore tested whether functional PRAME-specific cytotoxic T lymphocytes (PRAME CTLs) could be generated and expanded from healthy donors and CML patients, or whether the limited immunogenicity of this CTA coupled with tumor-associated anergy would preclude this approach.

Imatinib mesylate therapy in chronic myeloid leukemia patients in stable complete cytogenic response after interferon-alpha results in a very high complete molecular response rate.

To determine the impact on minimal residual disease by switching to imatinib chronic phase chronic myeloid leukaemia (CP-CML) patients responsive to interferon-alpha (IFNalpha), in stable complete cytogenetic response (CCR) but with persistent PCR positivity. Twenty-six Philadelphia positive (Ph+) CML patients in stable CCR after IFNalpha but persistently positive at PCR analysis during this treatment, were given imatinib mesylate at standard dose. At enrolment into the study, median IFN treatment and CCR duration were 88 months (range 15-202) and 73 months (range 10-148), respectively.

Rapid reversion of Loeffler's endocarditis by imatinib in early stage clonal hypereosinophilic syndrome.

Endomyocardial fibrosis (Loeffler's endocarditis) is the main cause of poor outcome in Hyper Eosinophilic Syndrome (HES) and Eosinophilic Leukemia (EL). Reversion of the cardiac damage has been seldom reported, and thrombi can superimpose on infiltrated walls, originating oembolic complications. The tyrosine kynase inhibitor imatinib has been recently employed in patients affected by HES or EL, with impressive results.

Expression of NK-associated antigens in extramedullary lymph nodal blast crisis of chronic myeloid leukemia on fine-needle cytology.

A case is reported of a 62-yr-old male suffering from chronic myelogenous leukemia (CML) who developed an extramedullary, para-orthic lymph-nodal blast crisis without blood or bone marrow involvement and expression of CD56/NK associated marker. The diagnosis was performed on ultrasound-guided fine-needle cytology by an immunocytochemical and flow cytometric analysis. Conventional smears showed a monomorphous population of disperse, undifferentiated cells without cytoplasm.