16 research outputs found
Impact of additional genetic abnormalities at diagnosis of chronic myeloid leukemia for first-line imatinib-treated patients receiving proactive treatment intervention
Early view: March 23, 2023The BCR::ABL1 gene fusion initiates chronic myeloid leukemia (CML), however evidence has accumulated from studies of highly selected cohorts that variants in other cancer-related genes are associated with treatment failure. Nevertheless, the true incidence and impact of additional genetic abnormalities (AGAs) at diagnosis of chronic phase (CP)-CML is unknown. We sought to determine whether AGAs at diagnosis in a consecutive imatinib-treated cohort of 210 patients enrolled in the TIDEL-II trial influenced outcome despite a highly proactive treatment intervention strategy. Survival outcomes including overall survival, progression-free survival, failure-free survival and BCR::ABL1 kinase domain mutation acquisition were evaluated. Molecular outcomes were measured at a central laboratory and included major molecular response (MMR, BCR::ABL1 ≤0.1%IS), MR4 (BCR::ABL1 ≤0.01%IS) and MR4.5 (BCR::ABL1 ≤0.0032%IS). AGAs included variants in known cancer genes and novel rearrangements involving the formation of the Philadelphia chromosome. Clinical outcomes and molecular response were assessed based on the genetic profile and other baseline factors. AGAs were identified in 31% of patients. Potentially pathogenic variants in cancer-related genes were detected in 16% of patients at diagnosis (including gene fusions and deletions) and structural rearrangements involving the Philadelphia chromosome (Ph-associated rearrangements), detected in 18%. Multivariable analysis demonstrated that the combined genetic abnormalities plus the ELTS clinical risk score were independent predictors of lower molecular response rates and higher treatment failure. Despite a highly proactive treatment intervention strategy, first-line imatinib-treated patients with AGAs had poorer response rates. This data provides evidence for the incorporation of genomically-based risk assessment for CML.Naranie Shanmuganathan, Carol Wadham, NurHezrin Shahrin, Jinghua Feng, Daniel Thomson, Paul Wang, Verity Saunders, Chung Hoow Kok, Rob M. King, Rosalie R. Kenyon, Ming Lin, Ilaria S. Pagani, David M. Ross, Agnes S.M. Yong, Andrew P. Grigg, Anthony K. Mills, Anthony P. Schwarer, Jodi Braley, Haley Altamura, David T. Yeung, Hamish S. Scott, Andreas W. Schreiber, Timothy P. Hughes and Susan Branfor
Uso da geotecnologia para caracterizar os cafezais no município de Londrina-PR, em relação à altimetria, declividade e tipo de solo
Viability and Quantification of Progenitor Cells in Venesected Blood from Patients Receiving Escalated-Dose Epirubicin and Cyclophosphamide with G-CSF for Lymphoma: Potential Role in Further Increasing Dose-Intensity
Estimation of haemopoietic progenitor cells in peripheral blood by the Advia 120 and BD vantage flow cytometer: a direct comparison for the prediction of adequate collections
NEW FOUR-COMPONENT UGI-TYPE REACTION. SYNTHESIS OF 3-METHYL-1-OXO-1,3,4,6,11,11a-HEXAHYDRO-2H-PYRAZINO[1,2-b]ISOQUINOLINE-3-CARBOXAMIDES
The dose of granulocyte colony‐stimulating factor administered following cytotoxic chemotherapy is not related to the rebound level of circulating CD34 +
Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte colony-stimulating factor (G-CSF): impact of age, sex, donor weight and type of G-CSF used
Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study
A prospective multicenter trial of peripheral blood stem cell sibling allografts for acute myeloid leukemia in first complete remission using fludarabine-cyclophosphamide reduced intensity conditioning
The role of allogeneic transplantation in patients with de novo acute myeloid leukemia in first complete remission (AML-CR1) is controversial. Aiming to preserve a graft-versus-leukemia effect, but minimize morbidity and mortality from conditioning-related toxicity and graft-versus-host disease (GVHD), we conducted a prospective multicenter study of reduced-intensity conditioning (RIC) as preparation for peripheral blood stem cell sibling allografts in patients with intermediate or poor risk AML-CR1. Conditioning consisted of fludarabine 125 mg/m(2) and cyclophosphamide 120 mg/kg. Thirty-four patients were transplanted with a median age of 45 years; 85% had intermediate risk cytogenetics. Early toxicity was minimal. The overall incidence of grade II-IV acute GVHD was low (21%), but the 3 patients (9%) who developed grade IV GVHD died. Donor T cell chimerism was rapid and generally complete, but complete myeloid chimerism was delayed. Thirteen patients (38%) relapsed, 12 within a year of transplant. The estimated disease-free survival (DFS) and overall survival at 2 years was 56% (95% confidence interval [CI] 39%-71%) and 68% (95% CI 50%-81%), respectively. The incidence of extensive chronic GVHD (cGVHD) was low (24% of surviving patients at 12 months) and most survivors had an excellent performance status. These observations justify a prospective comparison of RIC versus myeloablative conditioning allografts for AML-CR1.A.P. Grigg, J. Gibson, P.G. Bardy, J. Reynolds, P. Shuttleworth, R.L. Koelmeyer, J. Szer, A.W. Roberts, L.B. To, G. Kennedy and K.F. Bradstoc