More is less, less is more, or does it really matter? The curious case of impact of azacitidine administration schedules on outcomes in patients with myelodysplastic syndromes

AbstractMyelodysplastic syndromes (MDS) encompass a diverse group of hematologic disorders characterized by ineffective and malignant hematopoiesis, peripheral cytopenias and significantly increased risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine induce meaningful clinical responses in a significant subset of patients with MDS. Though never compared directly with decitabine, only azacitidine has improved overall survival (OS) compared to conventional care in a randomized trial in patients with higher-risk MDS. The azacitidine regimen used in this pivotal trial AZA-001 included administration at 75  mg/m2/day for 7 consecutive days in 28-day cycles (7 –0 regimen). Given the logistical difficulties of weekend administration in the 7–0 regimen, as well as in efforts to improve response rates, alternative dosing schedules have been used. In a typical 28-day cycle, administration schedules of 3, 5, 10, and (with the oral version of azacitidine) 1 4 and 21 days have been used in clinical trials. Most trials that evaluated alternative administration schedules of azacitidine did so in lower-risk MDS and did not directly compare to the 7–0 schedule. Given the lack of randomized prospective studies comparing the 7–0 schedule to the other reg imens of azacitidine in MDS, Shapiro et al. conducted a systematic review in an attempt to answer this question. Here we place the findings of this i...
Source: BMC Hematology - Category: Hematology Source Type: research

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Purpose of review By establishing mechanisms that deliver oxygen to sustain cells and tissues, fight life-threatening pathogens and harness the immune system to eradicate cancer cells, hematopoietic stem and progenitor cells (HSPCs) are vital in health and disease. The cell biological framework for HSPC generation has been rigorously developed, yet recent single-cell transcriptomic analyses have unveiled permutations of the hematopoietic hierarchy that differ considerably from the traditional roadmap. Deploying mutants that disrupt specific steps in hematopoiesis constitutes a powerful strategy for deconvoluting the comp...
Source: Current Opinion in Hematology - Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas and Sandrina Kinet Source Type: research
Condition:   Cancer Intervention:   Drug: PARP Inhibitors Sponsor:   University Hospital, Caen Active, not recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
CONCLUSION: This study showed the frequency and pattern of chromosomal abnormalities of MDS patients in upper northern Thailand were different from other populations. MDS with isolated chromosome 5 abnormalities had clinical characteristics corresponding with patients in good prognosis risk group. However, MDS patients with chromosome 7 and complex abnormalities showed higher percentage blast of BM which high risk to progression to acute myeloid leukemia (AML). Combined CC and FISH techniques detect chromosomal abnormalities with greater frequency than when either technique is used alone.. PMID: 32212788 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
ConclusionsWe conclude that oral AZA when combined with CDZ achieves successful tumor regression in both CDX and PDX models. Furthermore, the combination of AZA  + CDZ with VEN in a PDX model emulated responses seen with VEN + AZA in the clinic, implying a potential all-oral VEN-based therapy opportunity in myeloid diseases.
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
TheASXL1 mutation frequency is high in AML ‐MRC patients being its presence associated with specific characteristics, including morphological signs of dysplasia. This association raises the possible role ofASXL1 as a surrogate marker in AML ‐MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML‐MRC with intermediate‐risk kar yotype. AbstractAcute myeloid leukemia with myelodysplasia ‐related changes (AML...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
The distinction between myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) often relies on an arbitrary marrow blast cutoff of 30% in pediatrics and 20% in adults. There is little data about the treatment of children with extramedullary myeloid malignancy that has features of both, MDS and AML. Herein, we report for the first time 2 patients MDS/AML (1 with Shwachman-Diamond syndrome and 1 with idiopathic MDS and monosomy 7) who presented with extramedullary complications, received treatment with azacitidine, achieved complete remission and subsequently underwent hematopoietic stem cell transplantation.
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Original Articles Source Type: research
Conclusion: The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients. Primary Funding Source: Novartis Pharma AG. PMID: 32203980 [PubMed - as supplied by publisher]
Source: Annals of Internal Medicine - Category: Internal Medicine Authors: Tags: Ann Intern Med Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Cells become senescent in response to a variety of circumstances. The vast majority are cases of replicative senescence, somatic cells reaching the Hayflick limit. Cell damage and toxic environments also produce senescence, and senescent cells are also created as a part of the wound healing process. A senescent cell ceases replication and begins to secrete inflammatory and pro-growth signals, altering the nearby extracellular matrix and behavior of surrounding cells - even encouraging them to become senescent as well. Near all senescent cells last a short time only, as they self-destruct or are removed by the immune...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Authors: Shallis RM, Podoltsev NA, Gowda L, Zeidan AM, Gore SD Abstract Introduction: The myelodysplastic syndromes (MDS) vary in their risk of disease progression; progression includes increasingly severe bone marrow failure, reclassification as acute myeloid leukemia (AML), and death. Prognostic tools guide recommendations for allogeneic stem cell transplantation (alloSCT), the only curative option. AlloSCT is typically reserved for patients with higher-risk MDS as defined by existing prognostic tools, although additional clinical and biological factors in lower-risk patients may influence this dogma.Areas covere...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
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