Circulating tumor DNA (ctDNA) has become the most investigated analyte in blood. It is shed from the tumor into the circulation and represents a subset of the total cell-free DNA (cfDNA) pool released into the peripheral blood. In order to define if ctDNA could represent a useful tool to monitor hematologic malignancies, we analyzed 81 plasma samples from patients affected by different diseases.
View Article and Find Full Text PDFA deep and stable molecular response (DMR) is a prerequisite for a successful treatment-free remission (TFR) in chronic myeloid leukemia (CML). In order to better identify and analyze potential candidates of successful TFR, we examined the phenotypic and functional host immune compartment in DMR patients who had received TKI treatment only (TKI-only) or had been previously treated with interferon-alpha (IFNα + TKI) or had received IFNα treatment only (IFNα-only). The T/NK-cell subset distribution, NK- and T-cell cytokine production, activation and maturation markers were measured in 44 patients in DMR treated with IFNα only (9), with IFNα + TKI (11) and with TKI-only (24).
View Article and Find Full Text PDFCurr Cancer Drug Targets
September 2022
Background: The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Although outstanding results were achieved, about 20-30% of patients failed to achieve molecular milestones or experienced a severe toxicity and needed to switch to a second line.
View Article and Find Full Text PDFIntroduction: In chronic myeloid leukemia (CML) patients who have reached a deep and sustained reduction of residual disease can attempt a discontinuation. The 'treatment-free remission' (TFR) has become a real long-term endpoint for 30-40% of chronic phase patients.
Areas Covered: In this review, we focus our attention on possible prognostic features who can predict the success of tyrosine kinase inhibitors discontinuation and how we can assess the minimal residual disease (MRD) during the TFR phase.
Acta Oncol
November 2021
Background: A limited amount of data has been published in chronic-phase chronic myeloid leukemia (CP-CML) patients aged >75 years treated frontline with second-generation tyrosine kinase inhibitors.
Aims: To address this issue in a clinical 'real-life' setting, we retrospectively analyzed 45 CP-CML patients (pts) followed in 20 Italian Centers and treated frontline with dasatinib (DAS).
Patients And Methods: Median age was 78.
Background: Acute promyelocytic leukemia (APL) is uncommon among subjects aged ≥ 70 years and the better therapeutic strategy represents an unmet clinical need.
Materials And Methods: This prompted us to explore our real-life data on a retrospective cohort of 45 older APL patients (≥ 70 years) consecutively diagnosed at eight different hematologic institutions in Latium, Italy, from July 1991 to May 2019.
Results: Two patients (4.
Expert Opin Investig Drugs
August 2021
: Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. However, a subset of patients experienced resistance and/or intolerance and need to switch to other agents. Resistance to second-generation TKIs used in first-line treatment is less of an issue when compared to imatinib in first line.
View Article and Find Full Text PDFThe outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Prognostic stratification at baseline is part of a patient-centered approach to decide the best therapeutic approach.
View Article and Find Full Text PDFWe report the long-term outcome of 139 patients treated with imatinib in late chronic phase after IFN failure. Median follow-up was 16.6 years and the estimated 18-year OS was 64.
View Article and Find Full Text PDFTyrosine kinase inhibitors (TKIs), the backbone of treatment for chronic phase chronic myeloid leukemia patients (CP-CML), have changed the long-term outcome of the disease. Nonetheless, over 20% of patients fail front-line therapy due to intolerance or resistance. A head-to-head comparison of dasatinib and nilotinib as second-line treatment outside of sponsored clinical trials has not been reported.
View Article and Find Full Text PDFBackground: According to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 10/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 10/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET).
Patients And Methods: To validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 10/L) (124 patients; 76.
Tyrosine kinase inhibitors (TKIs) have drastically changed the outcome of chronic myeloid leukemia (CML) patients. A sustained and deep molecular response achieved over time paves the way to therapy discontinuation, and is a pre-requisite to attempt treatment-free remission. Monitoring of the molecular response during treatment discontinuation is routinely carried out by RQ-PCR, but it may not be the optimal tool to monitor minimal residual disease at the time of stopping treatment and during treatment discontinuation.
View Article and Find Full Text PDF: Tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, have significantly prolonged the overall survival of patients affected by chronic myeloid leukemia (CML) and changed drastically the outcome. Evidences from several studies suggest that in patients who have achieved a sustained, stable and deep molecular response, TKI treatment can be safely discontinued with a close subsequent monitoring. Thus, a stable deep molecular response (DMR) has become a feasible treatment goal in CML.
View Article and Find Full Text PDFIntroduction: Polycythemia vera is a myeloproliferative neoplasm characterized by an increased red blood cell mass, risk of thromboembolic events, and of transformation into secondary myelofibrosis and acute leukemia. The goal of treatment is to reduce the risk of fatal cardiovascular events reducing the hematocrit level with phlebotomies and low-dose aspirin. In high-risk patients (age >60 years or previous thromboembolic events) cytoreductive therapy is indicated.
View Article and Find Full Text PDFPrognostic role of chromosomal translocations (CT) in myelodysplasia (MDS) was retrospectively analyzed in 77 patients from GROM-L registry. Forty (51.9%) balanced, 28 (36.
View Article and Find Full Text PDFPredictive factors of response to hypomethylating agents (HMA) in elderly acute myeloid leukemia (AML) patients remain unclear in the real-life setting and no direct comparison between azacitidine (AZA) and decitabine (DEC) has been carried out. We retrospectively evaluated 110 AML patients treated with HMA (78 AZA, 32 DEC) as first-line therapy outside of clinical trials. Median age was 75 years (range 58-87).
View Article and Find Full Text PDFSince July 2017, different generic imatinib formulations have been introduced in Italy for the treatment of patients with chronic myeloid leukemia (CML). We analyzed 168 chronic phase CML patients treated with branded imatinib for a median of 12 years (range 1-16) at a single institution who switched to a single generic formulation in order to assess the safety and impact on molecular response. The Sokal risk was low/intermediate/high in 63%, 33%, and 4% of patients, respectively.
View Article and Find Full Text PDFMyelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by cytopenias and increased risk of acute leukemia transformation. Prognosis of MDS patients can be assessed by various scoring systems, the most common being the International Prognostic Scoring System (IPSS) now refined by the revised version (IPSS-R). Genomic information at baseline, that is currently not included in clinical prognostic scores, will, in the future, help us to stratify patients with various prognoses.
View Article and Find Full Text PDFBackground: In elderly patients with chronic myeloid leukemia (CML) responsive to imatinib, the incidence of clinically significant (CS) late chronic anemia is still unknown.
Materials And Methods: To highlight this issue, we revised retrospectively 81 CML patients aged >60 years treated at our Institution with front-line imatinib for at least 24 months in durable complete cytogenetic response (CCyR). CS late chronic anemia was defined as the presence of persistent (>6 months) and otherwise unexplained Hb levels ≤10 g/dL, which occurred >6 months from imatinib start.
The outcome of high-risk myelodysplastic syndrome (MDS) patients treated with 5-azacitidine (5-AZA) in the real-life setting remains largely unknown. We evaluated 110 MDS patients (IPSS intermediate 2/high) treated outside of clinical trials at a single institution between September 2003 and January 2017. Median duration of therapy was 9.
View Article and Find Full Text PDFImatinib, the first BCR/ABL kinase inhibitor approved for the treatment of chronic myeloid leukemia (CML), has changed the long-term outcome of patients affected by this disease. The aim of our analysis was to report, after a median follow-up of 10.2 years (range 5.
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