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1.
Clin Lymphoma Myeloma Leuk ; 21(2): 113-118, 2021 02.
Article in English | MEDLINE | ID: mdl-33422470

ABSTRACT

INTRODUCTION: Adults with acute myeloid leukemia (AML) have a high rate of remission; however, more than 50% relapse. C-kit is expressed in approximately 60% of patients with de novo AML and represents a potential therapeutic target. MATERIALS AND METHODS: Patients with newly diagnosed AML received 12 months of imatinib mesylate as maintenance therapy after the completion of post-remission therapy. The primary objective was to determine whether this approach improved progression-free survival (defined as no relapse and no death) compared with historical controls. RESULTS: The median progression-free survival of patients < 60 years of age was 52.1 months (historical control, 13 months) and for patients ≥ 60 years of age was 10.7 months (historical control, 8 months). The median level of AF1q expression was high (9.59), and 84% of patients had moderate or high levels of drug-resistance factors. CONCLUSIONS: Imatinib maintenance therapy may improve the outcome of newly diagnosed patients with AML who are < 60 years of age.


Subject(s)
Imatinib Mesylate/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Neoplasm Recurrence, Local/drug therapy , Protein Kinase Inhibitors/administration & dosage , Proto-Oncogene Proteins c-kit/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Female , Humans , Imatinib Mesylate/adverse effects , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Maintenance Chemotherapy/methods , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Progression-Free Survival , Protein Kinase Inhibitors/adverse effects , Proto-Oncogene Proteins c-kit/metabolism , Young Adult
2.
J Clin Oncol ; 35(14): 1591-1597, 2017 May 10.
Article in English | MEDLINE | ID: mdl-28350519

ABSTRACT

Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 5 , Leukemia, Myeloid, Acute/etiology , Myelodysplastic Syndromes/therapy , Aged , Aged, 80 and over , Anemia/etiology , Anemia/therapy , Antilymphocyte Serum/therapeutic use , Antineoplastic Agents/therapeutic use , Arsenic/therapeutic use , Azacitidine/analogs & derivatives , Azacitidine/therapeutic use , Cyclosporine/therapeutic use , Cytarabine/therapeutic use , Decitabine , Disease Progression , Enzyme Inhibitors/therapeutic use , Erythrocyte Transfusion , Female , Hematinics/therapeutic use , Humans , Hydroxyurea/therapeutic use , Immunologic Factors/therapeutic use , Lenalidomide , Male , Middle Aged , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/genetics , Recurrence , Retreatment , Retrospective Studies , Risk Factors , Survival Rate , Thalidomide/analogs & derivatives , Thalidomide/therapeutic use , Treatment Failure , Tretinoin/therapeutic use , Valproic Acid/therapeutic use
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