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Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation.

Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation. Int J Hematol. 2017 Nov 15;: Authors: Schroeder T, Rautenberg C, Haas R, Germing U, Kobbe G Abstract Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT. Furthermore, they have also been incorporated into prophylactic and pre-emptive approaches to avoid haematological relapse. In this review, we summarize the evidence from retrospective studies but also from a few prospective trials regarding the use of HMA after transplant. To aid clinicians in their daily clinical practice, we also comment on some practical aspects such as dosing and schedule, the choice of HMA and the use of complementary cellular therapies. Finally, this review also gives an overview on potential mechanisms mediating the efficacy of HMA after transplant as ...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research

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We report the case of a patient with MDS whose cytogenetic analysis showed spontaneous chromatid breakage (chrb): 46,XY,add(13)(q34),chtb(15)(q24) [3]/47,XY,chtb(2)(q22),del(5)(q35),del(7)(q32),+8,del(11q)(q23),del(q22)[cp17]. He was considered a high-risk patient due to the complex karyotype and the presence of chtb. We suggest that this chromosomal abnormality may be considered as a marker of genomic instability in MDS.RESUMO A s índrome mielodisplásica (SMD) é uma desordem clonal das células-tronco hematopoiéticas caracterizada por citopenias periféricas devido à hematopo...
Source: Jornal Brasileiro de Patologia e Medicina Laboratorial - Category: Pathology Source Type: research
AbstractMyelodysplastic syndromes (MDS) are heterogeneous clonal disorders ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukaemia. Comorbid conditions have rarely been systematically studied among patients with MDS. Older age per se has a negative impact on survival of MDS patients, in particular of those with lower risk. However, age indirectly affects also the survival of higher-risk patients by limiting their eligibility to intensive treatments. In addition, ageing is associated with an increasingly high risk of developing comorbidity, and a high prevalence of co...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
Contrary to initial reports, romiplostim treatment of thrombocytopenia does not appear to increase the risk of progression from myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML).Reuters Health Information
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Medscape Today News Source Type: news
Background: Studies of bone marrow cell clonal alterations in patients with Fanconi anemia (FA), a cancer-prone inherited bone marrow failure (BMF) syndrome, have focused on their role in progression from BMF to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The role of such alterations on patient outcomes after hematopoietic cell transplantation (HCT) is unknown.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Background: Azacitidine (Aza) and donor lymphocyte infusions (DLI) confer survival advantage with improved tolerability for patients with relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following allogenic stem cell transplantation (SCT).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Background: We tried to clarify the clinical significance of Wilms tumor gene-1 expression in peripheral blood cells (PB-WT1) for early detection of relapse in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Myelodysplastic syndrome (MDS) is an aging-associated group of clonal disorders characterized by ineffective hematopoiesis, leading to cytopenias and an increased risk of developing acute myeloid leukemia (AML). MDS arises from abnormal hematopoietic stem cells (HSCs). The only potentially curative therapy available for MDS patients is hematopoietic cell transplantation (HCT), but relapse is common, likely due to the inability of current therapies to effectively eliminate disease-initiating MDS HSCs.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Background: There are very limited data on the impact of BM fibrosis on prognosis and survival of AML and MDS especially after allogeneic HSCT. The current system of Reticulin Score for grading fibrosis according to (WHO 2008) is only semi-quantitative and subject to inter-observer inconsistency and no performance data. We evaluated BM fibrosis by a new objective and highly quantitative method of Computer-assisted Image Analysis (CIA) and correlated it to cytogenetics, survival and treatment-related mortality after allo-sib HSCT.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
CPX-351 is a dual-drug liposomal encapsulation of cytarabine (C) and daunorubicin (D) that delivers a synergistic 5:1 drug ratio and is FDA-approved for adults with newly diagnosed therapy-related AML or AML with MDS-related changes. In a randomized, phase 3 study (NCT01696084) in patients (pts) 60-75 y with newly diagnosed sAML, CPX-351 significantly improved overall survival (OS) and remission rates vs 7  + 3. RAEB-t AML, often defined as bone marrow blasts 20%-29%, shares many features with myelodysplastic syndrome (MDS).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Background: Patients (pts) with High-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) often proceed to allogeneic hematopoietic stem cell transplant (alloHSCT) due to poorer outcomes. This is the only chance of cure; however, relapse rates after alloHSCT remain high and range between 25-50%. Maintenance approaches post-HSCT, such as hypomethylating agents or tyrosine kinase inhibitors, have been used to decrease the relapse rate with mixed results. Lenalidomide is known to augment T/NK cell activity/proliferation which lead us to hypothesize that it will enhance the Graft-versus-Leukemia (GvL) effect wit...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
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