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Function: _error_handler
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Function: _error_handler
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Function: insertAPISummary
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Function: formatAIDetailSummary
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Radotinib (IY5511HCL), a novel and selective BCR-ABL1 tyrosine kinase inhibitor, has shown pre-clinical and phase I activity and safety in chronic myeloid leukemia. This phase II study investigated the efficacy and safety of radotinib in Philadelphia chromosome-positive chronic phase-chronic myeloid leukemia patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Patients received radotinib 400 mg twice daily for 12 cycles based on results from the phase I trial. The primary end point was rate of major cytogenetic response by 12 months. A total of 77 patients were enrolled. Major cytogenetic response was achieved in 50 (65%; cumulative 75%) patients, including 36 (47%) patients with complete cytogenetic response by 12 months. Median time to major cytogenetic response and complete cytogenetic response were 85 days and 256 days, respectively. Major cytogenetic response and complete cytogenetic response rates were similar between imatinib-resistant and imatinib-intolerant patients, but were higher in patients without BCR-ABL1 mutations. Overall and progression-free survival rates at 12 months were 96.1% and 86.3%, respectively. All newly-occurring or worsening grade 3/4 hematologic abnormalities included thrombocytopenia (24.7%) and anemia (5.2%); grade 3/4 drug-related non-hematologic adverse events included fatigue (3.9%), asthenia (3.9%), and nausea (2.6%). The most common biochemistry abnormality was hyperbilirubinemia (grade 3/4 23.4%), and 12 of 18 cases were managed with dose modification. Study findings suggest radotinib is effective and well tolerated in chronic phase-chronic myeloid leukemia patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase inhibitors and may represent a promising alternative for these patients. (clinicaltrials.gov identifier: 01602952).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077080 | PMC |
http://dx.doi.org/10.3324/haematol.2013.096776 | DOI Listing |
Am J Hematol
December 2024
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Patients who develop acute myeloid leukemia (AML) after having received treatment for myelodysplastic syndrome (MDS) or related conditions have particularly poor outcomes. This study analyzed adult patients with newly diagnosed AML who previously had MDS, chronic myelomonocytic leukemia (CMML), or MDS/myeloproliferative neoplasm (MPN) overlap syndrome, and who had received hypomethylating agents, chemotherapy, and/or allogeneic stem cell transplantation (HSCT) for these antecedent disorders. From January 2012 to August 2023, we included 673 patients with a median age of 70 years (range, 19-94); 536 (80%) had transformed from MDS, and the remainder from CMML or MDS-MPN.
View Article and Find Full Text PDFClin Genet
December 2024
Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
Ataxia with Vitamin E Deficiency (AVED) is a rare autosomal recessive genetic disorder, that caused by pathogenic variants in the TTPA gene, which encodes the alpha-tocopherol transfer protein. This study investigates eight patients from three consanguineous Iranian families, using exome sequencing (ES) and Sanger sequencing to identify novel pathogenic variants in the TTPA gene. Two variants were identified: c.
View Article and Find Full Text PDFCancers (Basel)
November 2024
Centro de Investigación del Cáncer, IBMCC, CSIC, Universidad de Salamanca, IBSAL (Instituto de Investigación Biomédica de Salamanca) Campus, Miguel de Unamuno, 37007 Salamanca, Spain.
Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the clonal expansion of abnormal lymphoid precursors in bone marrow, which leads to alterations in the processes of cell differentiation and maturation as a consequence of genetic alterations. The integration of conventional methods, such as cytogenetics and immunophenotyping, and next-generation sequencing (NGS) has led to significant improvements at diagnosis and patient stratification; this has also allowed the discovery of several novel molecular entities with specific genetic variants that may drive the processes of leukemogenesis. Nevertheless, the understanding of the process of leukemogenesis remains a challenge since this disease persists as the most frequent cancer in children; it accounts for approximately one-quarter of adult acute leukemias, and the patient management may take into consideration the high intra- and inter-tumor heterogeneity and the relapse risk due to the various molecular events that can occur during clonal evolution.
View Article and Find Full Text PDFBackground: The introduction of proteasome inhibitors (PIs) and lenalidomide as treatment for newly diagnosed multiple myeloma (MM) has led to an increased population of lenalidomide-refractory patients. Limited data are available characterizing current treatments and outcomes in this difficult-to-treat population.
Methods: Individual patient-level data were analyzed from the treatment arms of multiple daratumumab studies, including APOLLO, CASTOR, CANDOR, EQUULEUS, ALCYONE, MAIA, GRIFFIN, POLLUX, and CASSIOPEIA.
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