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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SUMMARY Granulocytic sarcoma also called myeloid sarcoma is an extramedullary tumour of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukaemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukaemia and myelodysplastic syndromes. Here, we report a case of a 60-year-old male with past history of myelofibrosis admitted to the emergency room due ulceronecrotic lesions, fever and dysphagia. We emphasize the importance of recognizing this entity and its severity.RESUMO O sarcoma granuloc ítico, também chamado de sarcoma ...
Source: Revista da Associacao Medica Brasileira - Category: General Medicine Source Type: research
SUMMARY Granulocytic sarcoma also called myeloid sarcoma is an extramedullary tumour of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukaemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukaemia and myelodysplastic syndromes. Here, we report a case of a 60-year-old male with past history of myelofibrosis admitted to the emergency room due ulceronecrotic lesions, fever and dysphagia. We emphasize the importance of recognizing this entity and its severity.RESUMO O sarcoma granuloc ítico, também chamado de sarcoma ...
Source: Revista da Associacao Medica Brasileira - Category: General Medicine Source Type: research
Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome, Published online: 16 December 2018; doi:10.1038/s41375-018-0312-9Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome
Source: Leukemia - Category: Hematology Authors: Source Type: research
Authors: Ding WJ, Yang Y, Chen ZX, Wang YY, Dong WL, Cen JN, Qi XF, Jiang F, Chen SN Abstract Previous studies on the pathogenesis of myelodysplastic syndrome (MDS) have identified multiple associated gene mutations, including mutations of tetmethylcytosinedioxygenase 2, isocitrate dehydrogenase [NADP(+)] 1 cytosolic, isocitrate dehydrogenase [NADP(+)] 2 mitochondrial and additional sex combs like 1 transcriptional regulator, all of which may be considered epigenetic regulators. Furthermore, mutations of RAS type GTPase family genes have been identified in 10-15% patients with MDS. The authors' previous study on th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
The search for the optimal conditioning regimen prior to allogeneic hematopoietic stem cell transplant (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has been ongoing for decades.[1, 2] Early conditioning regimens consisted of high-dose chemotherapy and radiation, now characterized as myeloablative conditioning (MAC), to achieve the aspired outcome of eliminating malignant disease with concomitant restoration of normal hematopoiesis. With experience and improved understanding of the graft-versus-leukemia effect, investigators began to lower the intensity of conditioning regimens.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Authors: Masarova L, Kantarjian H, Ravandi F, Sharma P, Garcia-Manero G, Daver N Abstract In the past few years, our improved understanding of the pathogenesis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has led to remarkable advances in the development of novel therapeutic approaches for these diseases. This chapter summarizes the available clinical data with immune-based therapeutic modalities in AML and MDS, focusing on monoclonal antibodies, T cell engager antibodies, chimeric antigen receptor (CAR)-T cells, and checkpoint blockade via blockade of PD-1/PD-L1 or CTLA4. Numerous clinical tr...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Azacitidine may delay or prevent relapse among patients with MRD-positive acute myeloid leukemia or myelodysplastic syndrome.
Source: CancerNetwork - Category: Cancer & Oncology Authors: Source Type: news
Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome &low blast acute myeloid leukemia. Haematologica. 2018 Dec 13;: Authors: Kenealy M, Hertzberg M, Benson W, Taylor K, Cunningham I, Stevenson W, Hiwase D, Eek R, Zantomio D, Jong S, Wall M, Blombery P, Gerber T, Debrincat M, Zannino D, Seymour JF, Australasian Leukaemia and Lymphoma Group Abstract Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outco...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Conditions:   Recurrent Acute Myeloid Leukemia;   Recurrent Myelodysplastic Syndrome;   Refractory Acute Myeloid Leukemia;   Refractory Myelodysplastic Syndrome Interventions:   Drug: Belinostat;   Drug: Pevonedistat Sponsor:   National Cancer Institute (NCI) Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract Dacogen, the formulated product of the pharmaceutically active agent decitabine (5 aza-2'-deoxycytidine), is approved for treatment of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). The current analysis was performed to characterize the pharmacokinetics of decitabine in pediatric patients with AML and evaluate their consistency with the PK in adult patients. A population pharmacokinetic model was developed by pooling decitabine concentration-time data from 5 adult (AML and MDS) and 2 pediatric (AML) studies. A total of 840 concentration-time data points obtained from 71 adults and 28 p...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research
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