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Epigenetic Combination Therapy for Children With Secondary Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) and Concurrent Solid Tumor Relapse

Secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is a rare but devastating complication of solid tumor treatment involving high-dose topoisomerase II inhibitor and alkylator chemotherapy. For relapsed or elderly MDS and AML patients ineligible for hematopoietic stem cell transplantation, epigenetic therapies, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been utilized as palliative therapy, offering a well-tolerated approach to disease stabilization, prolonged survival, and quality of life. Literature on the use of epigenetic therapies for both primary and relapsed disease is scarce in the pediatric population. Here, we report 2 pediatric patients with secondary AML and MDS, respectively, due to prior therapy for metastatic solid tumors. Both patients were ineligible for hematopoietic stem cell transplantation due to concurrent solid tumor relapse, but were treated with the epigenetic combination therapy, decitabine and vorinostat, and achieved stabilization of marrow disease, outpatient palliation, and family-reported reasonable quality of life.
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Original Articles Source Type: research

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This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year ...
Source: The Korean Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Korean J Intern Med Source Type: research
CONCLUSIONSAdjuvant chemotherapy is associated with a small but significant increase in the risk of AML and MDS, especially with regimens that include A. Longer follow‐up is needed to confirm that risk is not increased with the recently adopted TC regimen. Cancer 2017. © 2017 American Cancer Society.
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
In this study (ASPIRE), we aimed to assess eltrombopag, an oral thrombopoietin receptor agonist, for thrombocytopenia (grade 4) treatment in adult patients with advanced MDS or AML. Methods ASPIRE consisted of an open-label, double-blind phase for 8 weeks and a randomised, double-blind phase (parts 1 and 2, reported here) for 12 weeks, and an open-label extension (part 3). Eligible patients were men and women aged 18 years or older, with intermediate-2 or high-risk MDS or AML, with bone marrow blasts of 50% or less, and had either grade 4 thrombocytopenia due to bone marrow insufficiency (platelet counts <25 ×...
Source: The Lancet Haematology - Category: Hematology Source Type: research
Authors: Alter BP Abstract Patients with inherited bone marrow failure syndromes are usually identified when they develop hematologic complications such as severe bone marrow failure, myelodysplastic syndrome, or acute myeloid leukemia. They often have specific birth defects or other physical abnormalities that suggest a syndrome, and sequencing of specific genes or next-generation sequencing can determine or confirm the particular syndrome. The 4 most frequent syndromes are Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond syndrome. This review discusses the major complications...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: West AH, Churpek JE Abstract Patients with inherited bone marrow failure syndromes (IBMFSs) classically present with specific patterns of cytopenias along with congenital anomalies and/or other physical features that are often recognizable early in life. However, increasing application of genomic sequencing and clinical awareness of subtle disease presentations have led to the recognition of IBMFS in pediatric and adult populations more frequently than previously realized, such as those with early onset myelodysplastic syndrome (MDS). Given the well-defined differences in clinical management needs and outc...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Conclusion: Low‐intensity chemotherapy, i.e. HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1 and/or IDH1/2 mutations. This article is protected by copyright. All rights reserved.
Source: American Journal of Hematology - Category: Hematology Authors: Tags: Research Article Source Type: research
There is currently a conundrum regarding the differentiation of acute myeloid leukemia and myelodysplastic syndromes. In this interview, Stphane de Botton, MD, PhD of the Gustave Roussy Institute, Vi... Author: VJHemOnc Added: 12/07/2017
Source: Oncology Tube - Category: Cancer & Oncology Source Type: podcasts
Conclusions: Posttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment. PMID: 29228125 [PubMed - as supplied by publisher]
Source: American Journal of Clinical Pathology - Category: Pathology Authors: Tags: Am J Clin Pathol Source Type: research
AbstractImmunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. ...
Source: Annals of Hematology - Category: Hematology Source Type: research
Abstract Disease overviewThe myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DiagnosisDiagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis. Ri...
Source: American Journal of Hematology - Category: Hematology Authors: Tags: ANNUAL CLINICAL UPDATES IN HEMATOLOGICAL MALIGNANCIES Source Type: research
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