Clonal hematopoiesis of indeterminate potential–associated mutations and risk of comorbidities in patients with myelodysplastic syndrome

Naqvi, Kiran; Sasaki, Koji; Montalban‐Bravo, Guillermo; Piérola, Ana Alfonso; Yılmaz, Musa; Short, Nicholas J.; Assi, Rita; Jabbour, Elias; Ravandi, Farhad; Kadia, Tapan M.; Pierce, Sherry; Takahashi, Koichi; González, Graciela Nogueras; Kanagal‐Shamanna, Rashmi; Patel, Keyur P.; Soltysiak, Kelly A.; Kantarjian, Hagop M.

doi:10.1002/cncr.32056

Cited by 17 publications

(13 citation statements)

References 23 publications

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“…It is important to emphasize that a majority of patients with MDS will die from complications of MDS without transforming to AML and therefore the need for unique treatment strategies for patients with MDS 8 . Further adding importance to this concept is the discovery of the relation between comorbidities and clonal hematopoiesis 9 and MDS 10 suggesting an interplay between MDS and the development of other conditions, such as cardiovascular disease 11…”

Section: Disease Overviewmentioning

confidence: 99%

Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management

2020

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Disease overview: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). Myelodysplastic syndromes occur more frequently in older males and in individuals with prior exposure to cytotoxic therapy. Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry and molecular genetics is usually complementary and may help refine diagnosis. Risk-stratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic characteristics. The most commonly accepted system is the Revised International Prognostic Scoring System (IPSS-R). Somatic mutations can help define prognosis and therapy. Risk-adapted therapy: Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, cytogenetic and mutational profiles, comorbidities, potential for allogeneic stem cell transplantation (alloSCT) and prior exposure to hypomethylating agents (HMA). Goals of therapy are different in lower-risk patients than in higher-risk individuals and in those with HMA failure. In lower-risk MDS, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher-risk disease, the goal is to prolong survival. In 2020, we witnessed an explosion of new agents and investigational approaches. Current available therapies include growth factor support, lenalidomide, HMAs, intensive chemotherapy and alloSCT. Novel therapeutics approved in 2020 are luspatercept and the oral HMA ASTX727. At the present time, there are no approved interventions for patients with progressive or refractory disease particularly after HMA-based therapy. Options include participation in a clinical trial, cytarabine-based therapy or alloSCT.

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Section: Disease Overviewmentioning

confidence: 99%

Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management

2020

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“…The mean age of patients with vascular disease was also higher (72 vs 66 years, P = 0.001). Base- Reducing variability by using the square root of the ferritin value has been proposed by prior authors [11] Two retrospective studies (N = 77 [13] and N = 566 [14]) were conducted at outside institutions to study the link between MDS and TA B L E 2 Associations of MDS variables with vascular events. (A) shows data for the entire cohort of MDS patients, (B) shows data for patients with MDS with low risk of progression, and (C) shows data for patients with MDS with high risk of progression .746 cardiovascular disease.…”

Section: Resultsmentioning

confidence: 99%

Predictors of vascular disease in myelodysplastic syndromes

Faber

Lloyd

Singh

et al. 2020

eJHaem

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The escalating link between somatic mutations commonly seen in myelodysplastic syndromes (MDS) and atherosclerotic vascular disease has increased the interest in management and associations of these conditions. We present a retrospective study examining clinical and molecular variables associated with vascular disease in patients with MDS. This study included a comprehensive evaluation of 236 patients with MDS. Our study has multiple findings. Mutations in ASXL1 correlated with increased risk of vascular disease for the entire cohort (P = .013). Though this has been replicated in other studies, there are no guidelines at this time for preventing vascular events in these patients. Our study also showed that lower ferritin levels may be linked to increased vascular events (P = .043), therefore the optimal use of supportive red blood cell transfusions in patients with MDS and the overall impact of inflammatory markers such as erythrocyte sedimentation rate and c‐reactive protein should be re‐addressed. Furthermore, our study showed that patients with Trisomy 8 in the low‐risk MDS cohort (based on IPSS‐R scores) were protected from vascular events (P = .036). Our findings of lower ferritin being linked with increased risk of vascular events as well as patients with Trisomy 8 being protected from vascular events may impact patient care. There do not appear to be any prior studies with these findings. In addition, given the connection between MDS and atherosclerotic vascular disease, we believe guideline‐based management of cardiac risk factors among MDS patients may improve overall outcomes. Further studies with larger patient cohorts are needed to further investigate these findings.

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“…Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) generally affect older individuals with a median age at diagnosis of 68 years and increasing frequency in individuals aged > 70-80 years [55]. Given the high risk of severe CO-VID-19 disease observed in older individuals, particularly with comorbidities, it should be factored in the treatment decisions on most patients with MDS [56][57][58]. Therefore, irrespective of the degree of neutropenia, all patients with MDS or MDS/MPN should be considered at high risk for complicated COVID-19, and medical comorbidities should be aggressively managed both in CO-VID-19-negative and -positive patients.…”

Section: Myelodysplastic Syndromes and Myelodysplastic/ Myeloprolifermentioning

confidence: 99%

Treating Leukemia in the Time of COVID-19

et al. 2020

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The coronavirus disease 2019 (COVID-19) pandemic poses several challenges to the management of patients with leukemia. The biology of each leukemia and its corresponding treatment with conventional intensive chemotherapy, with or without targeted therapies (venetoclax, FLT3 inhibitors, IDH1/2 inhibitors, Bruton's tyrosine kinase inhibitors), introduce additional layers of complexity during COVID-19 highrisk periods. The knowledge about COVID-19 is accumulating rapidly. An important distinction is the prevalence of "exposure" versus "clinical infectivity," which determine the risk versus benefit of modifying potentially highly curative therapies in leukemia. At present, the rate of clinical infection is < 1-2% worldwide. With a mortality rate of 1-5% in CO-VID-19 patients in the general population and potentially of > 30% in patients with cancer, careful consideration should be given to the risk of COVID-19 in leukemia. Instead of reducing patient access to specialized cancer centers and modifying therapies to ones with unproven curative benefit, there is more rationale for less intensive, yet effective therapies that may require fewer clinic visits or hospitalizations. Here, we offer recommendations on the optimization of leukemia management during high-risk COVID-19 periods.

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Clonal hematopoiesis of indeterminate potential–associated mutations and risk of comorbidities in patients with myelodysplastic syndrome

Cited by 17 publications

References 23 publications

Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management

Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management

Predictors of vascular disease in myelodysplastic syndromes

Treating Leukemia in the Time of COVID-19

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