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.
Condition: Leukaemia Intervention: Drug: SAR440234 Sponsor: Sanofi Not yet recruiting
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) developing in persons exposed to DNA-damaging agents for a prior cancer are often referred to as treatment- or therapy-related myeloid neoplasms (t-MN)[1,2]. t-MN constitute approximately 10-20% of all cases of AML and MDS, a proportion that may increase in the future with an increasing prevalence of cancer survivors[4,5]. Hematopoietic cell transplants (HCT) use high doses of drugs and/or ionizing radiations and can also lead to t-MN[6,7].
Downregulation of microRNA‑21 expression inhibits proliferation, and induces G1 arrest and apoptosis via the PTEN/AKT pathway in SKM‑1 cells. Mol Med Rep. 2018 Jul 05;: Authors: Li G, Song Y, Li G, Ren J, Xie J, Zhang Y, Gao F, Mu J, Dai J Abstract Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and may progress to acute myeloid leukemia (AML). MicroRNAs (miRNA/miRs) as oncogenes or tumor suppressors regulate a number of biological processes including cell proliferation, cell cycle and apoptosis in different types of cancer cells. Recently, it has been reported that m...
Publication date: Available online 17 July 2018Source: The Lancet HaematologyAuthor(s): Mark P Little, Richard Wakeford, David Borrego, Benjamin French, Lydia B Zablotska, M Jacob Adams, Rodrigue Allodji, Florent de Vathaire, Choonsik Lee, Alina V Brenner, Jeremy S Miller, David Campbell, Mark S Pearce, Michele M Doody, Erik Holmberg, Marie Lundell, Siegal Sadetzki, Martha S Linet, Amy Berrington de GonzálezSummaryBackgroundSubstantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (
In conclusion, incidence of breakthrough IFI was low among patients receiving posaconazole prophylaxis, and not significantly different between patients receiving the tablet versus oral suspension formulations. PMID: 30012757 [PubMed - as supplied by publisher]
Therapy related myeloid neoplasm (t-MN) is an emerging challenge in the current era given that newer therapies are improving the life expectancy of patients diagnosed with cancer. This condition arises as a result of exposure to prior chemotherapy or radiotherapy used to treat malignant or non-malignant conditions. The World Health Organization (WHO) 2001 classification of tumors of hematopoietic and lymphoid tissues had initially described this disorder with two subtypes – therapy related acute myeloid leukemia (t-AML) and therapy related myelodysplastic syndrome (t-MDS) 1.
Application of next-generation sequencing (NGS) panels is usually limited to diagnosis, prognosis, and development of personalized treatment strategies/targeted therapies for patients with myeloid malignancies e.g., Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), and acute myelogenous leukemia (AML). Here we present a case of 3 year old male that presented with pancytopenia and splenomegaly. His initial bone marrow revealed mild to moderate fibrosis (normocellular; no increase in blasts).
We report a myelodysplastic syndrome (MDS) patient who presented Fusarium solani infection associated with granulocytic sarcoma as an initial presentation of acute myeloid leukemia (AML) transformation. We performed histological examination, immunohistochemistry analysis, culture of the biopsy tissue and DNA sequencing to make a conclusive diagnosis of F. solani and granulocytic sarcoma, reinforcing the necessity of performing complete evaluation of skin lesions in immunocompromised patients.
Myelodysplastic syndrome (MDS) is rare in the pediatric age group and it may be associated with inheritable bone marrow failure (BMF) such as Fanconi anemia (FA). FA is a rare multi-system genetic disorder, ch...
We present a 2-year-old boy with splenomegaly, leukocytosis, thrombocytopenia, anemia, and excess myeloblasts with easily seen Auer rods, and marked dysgranulopoiesis and dyserythropoiesis. Conventional cytogenetic analysis showed a sole abnormality of t(3;5)(q25;q35). Microarray analysis showed a terminal 21 Mb region of copy-neutral loss of heterozygosity on 19q. Disease-related somatic NRAS mutation was detected. This case represents an unusual JMML with Auer rods and marked myelodysplasia. These unusual histopathologic features may be related to the t(3;5)(q25;q35). A t(3;5) with variable breakpoints has been reported ...