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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AbstractRecently, an immunodeficiency syndrome caused by guanine-adenine-thymine-adenine 2 (GATA2) deficiency has been described. The syndrome is characterized by (i) typical onset in early adulthood, (ii) profound peripheral blood cytopenias of monocytes, B lymphocytes, and NK cells, (iii) distinct susceptibility to disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections (particularly human papillomavirus), and (iv) a high risk of developing hematologic malignancies (myelodysplastic syndromes (MDS); acute myeloid leukemias (AML)). Considerable clinical heterogeneity exists among patients withGA...
Source: Annals of Hematology - Category: Hematology Source Type: research
Myelodysplastic syndromes (MDS) are a series of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a propensity to transform to acute myeloid leukemia (AML) [1]. AML is a myeloid malignancy characterized by increased self-renewal, limited differentiation and deregulated proliferation of myeloid blasts. They may cause bone marrow failure and death within months or even weeks if diagnosis and treatment time is delayed. Recent studies showed that demethylating agents 5-azacytidine (AZA) and 5-aza-2-deoxycytidine (decitabine, DAC) may bring substantial survival...
Source: Leukemia Research - Category: Hematology Authors: Source Type: research
Various myeloid neoplasms, including the myelodysplastic syndromes (MDS), bear a certain risk of progression to secondary acute myeloid leukemia (sAML). The evolution from low-risk to high-risk MDS and finally to sAML suggests that leukemogenesis is a multistep process. However, even before an overt neoplasm, such as an MDS, develops, “prediagnostic” clonal conditions may be identified. With the advent of large-scale genomic screens, such conditions may be detected quite frequently and early in apparently healthy individuals. Recent data suggest that these conditions increase with age and are indeed associated ...
Source: Pathobiology - Category: Pathology Source Type: research
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases of ineffective hematopoiesis with a risk for progression to acute myeloid leukemia (AML) [1,2]. More than 80% of individuals with MDS are 65 years old or older at the time of diagnosis [3]; the average age at diagnosis is 67 years old [4]. Anemia and fatigue are common in MDS, and are often managed through red blood cell transfusions. In addition, MDS can transform into AML requiring intensive chemotherapy and prolonged hospital stays of approximately 30 days [5], which can lead to severe toxicities and functional impairments [5 –8].
Source: Leukemia Research - Category: Hematology Authors: Source Type: research
Myelodysplastic syndromes (MDS) is a heterogeneous group of hematopoietic stem cell disorders that are characterized by cytopenia and dysplastic changes in peripheral blood (PB) and bone marrow (BM) and a propensity to transform into acute myeloid leukemia (AML) [1]. The diagnosis of MDS is based on cytomorphology and cytogenetics. Good cytomorphological experience is required for a correct diagnosis of MDS, particularly lower-risk MDS. The French-American-British (FAB) classification [2] was the standard.
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
International Journal of Urology, EarlyView.
Source: International Journal of Urology - Category: Urology & Nephrology Authors: Source Type: research
Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells that mainly affect the elderly, characterized by ineffective hematopoiesis, leading to cytopenia, infections, and a significant reduction in the quality of life [1,2]. Intensive chemotherapy combined with hematopoietic stem cell transplantation (HSCT) is the only curative treatment for this disease. However, it's applicability in elderly patients is limited by comorbidities and poor performance status. Azacytidine (AZA) significantly reduces transfusion dependence, decreases the risk of transformation to acute myeloid leukemia (AML), and impro...
Source: Experimental Hematology - Category: Hematology Authors: Tags: Brief Communication Source Type: research
Polycythemia Vera (PV) is a BCR-ABL negative myeloproliferative neoplasm characterized by the proliferation of red blood cells, although white blood cells and platelets are often also elevated. [1] Mutations of Janus Kinase 2 (JAK2), particularly JAK2V617F, are present in 98% of PV patients.[2] The natural history of PV includes progression to myelofibrosis (MF), myelodysplastic syndrome or acute myeloid leukemia (AML) at a rate of 1.3 progressions per 100 patient-years.[3] Untreated life expectancy is 6 to 18 months.[1] Lifespan is extended with treatment, although mortality is still about 1.6 times higher than age-matched controls.[4],[5]
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
Various myeloid neoplasms, including the myelodysplastic syndromes (MDS), bear a certain risk of progression to secondary acute myeloid leukemia (sAML). The evolution from low-risk to high-risk MDS and finally to sAML suggests that leukemogenesis is a multistep process. However, even before an overt neoplasm, such as an MDS, develops, “prediagnostic” clonal conditions may be identified. With the advent of large-scale genomic screens, such conditions may be detected quite frequently and early in apparently healthy individuals. Recent data suggest that these conditions increase with age and are indeed associated ...
Source: Pathobiology - Category: Pathology Source Type: research
PMID: 29866886 [PubMed - in process]
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
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