Cause of death in patients with lower‐risk myelodysplastic syndrome

Dayyani, Farshid; Conley, Anthony P.; Strom, Sara S.; Stevenson, William; Cortes, Jorge; Borthakur, Gautam; Faderl, Stefan; O’Brien, Susan; Pierce, Sherry; Kantarjian, Hagop M.; Garcia‐Manero, Guillermo

doi:10.1002/cncr.24984

Cited by 132 publications

(124 citation statements)

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“…This concept is being modified by the better understanding of the natural progression of MDS and the development of new therapies. Another important concept is that a large majority of patients with MDS die from causes intrinsic to the disease and not due to progression to AML [6]. This has important implications for the development of therapies in MDS.…”

Section: Guillermo Garcia-maneromentioning

confidence: 99%

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Garcia‐Manero

2012

American J Hematol

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Disease Overview: The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male 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 or molecular genetics is complementary but not diagnostic.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 used system is the International Prognostic Scoring System. IPSS is likely to be replaced by a new revised score (IPSS‐R) and by the incorporation of new molecular markers recently described.Risk‐adapted therapy: Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts, and, more recently, cytogenetic profile. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia and a chromosome 5 alteration. 5‐azacitidine and decitabine have activity in higher risk MDS. 5‐azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation.Management of progressive or refractory disease: At the present time there are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include cytarabine based therapy, transplantation and participation on a clinical trial. Am. J. Hematol. 87:692–701, 2012. © 2012 Wiley Periodicals, Inc.

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Section: Guillermo Garcia-maneromentioning

confidence: 99%

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Garcia‐Manero

2012

American J Hematol

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“…2 Furthermore, the cause of death in patients with lower-risk disease is more commonly related to complications intrinsic to MDSs (particularly infection) rather than transformation to acute myeloid leukemia (AML). 3 Recent data also indicate that poor prognosis mutational events are common in patients with poor-risk or lower-risk MDSs. 4,5 These data suggest the need for the development of treatment strategies for specific subsets of patients with lower-risk and poor-risk MDSs.…”

Section: Introductionmentioning

confidence: 99%

Randomized Open-Label Phase II Study of Decitabine in Patients With Low- or Intermediate-Risk Myelodysplastic Syndromes

Garcia‐Manero

Jabbour

Borthakur

et al. 2013

JCO

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A B S T R A C T PurposeThis open-label, randomized phase II trial assessed efficacy and tolerability of two low-dose regimens of subcutaneous (SC) decitabine in patients with low-or intermediate-1-risk myelodysplastic syndrome (MDS). Patients and MethodsPatients received decitabine 20 mg/m 2 SC per day for 3 consecutive days on days 1, 2, and 3 every 28 days (schedule A) or 20 mg/m 2 SC per day once every 7 days on days 1, 8, and 15 every 28 days (schedule B) for up to 1 year. Primary efficacy end point was overall improvement rate (OIR:. Secondary end points were HI, transfusion independence, cytogenetic response, overall survival (OS), and time to acute myeloid leukemia or death. ResultsEfficacy and safety populations were identical: schedule A, n ϭ 43; schedule B, n ϭ 22. Median time from MDS diagnosis to treatment was 3.6 months; 89% had de novo MDS. The trial was terminated early on achievement of protocol-defined OIR superiority of schedule A over schedule B; OIR was 23% for schedule A (seven CRs, three HIs) and 23% for schedule B (one mCR, one PR, three HIs). No differences were observed in secondary end points. Median OS was not reached; approximately 70% of patients were alive at 500 days. Patients in schedule A (67%) and schedule B (59%) were RBC/platelet independent on study. The most frequent drug-related adverse events overall were neutropenia (28% v 36%), anemia (23% v 18%), and thrombocytopenia (16% v 32%).

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“…The median survival in patients diagnosed with higher risk forms of the disease is <2 years, and MDS-associated complications are the leading cause of death even among lower risk patients. 6,17 Whereas an incomplete pathobiologic understanding of MDS by the biomedical community and the paucity of available highly effective MDS treatments are the major factors contributing to these poor outcomes, suboptimal use of currently available therapies, incomplete understanding of disease by patients and HCPs, and premature discontinuation of potentially effective treatments may also be important factors influencing MDS-associated outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Most patients with MDS-even those with lower risk disease features at the time of diagnosis-will die of infectious or hemorrhagic complications related to their disease. 6,7 The only potentially curative therapy, allogeneic hematopoietic stem cell transplantation (HSCT), is currently attempted in less than 5% of patients because of the advanced age and comorbid conditions present in most patients and perceptions about the danger of HSCT. 8,9 There are currently 3 drugs approved for MDS by the US Food and Drug Administration (FDA) that offer symptomatic benefit and slow disease progression in some patients: azacitidine (AZA), decitabine (DAC), and lenalidomide (LEN).…”

Section: Introductionmentioning

confidence: 99%

Disparity in perceptions of disease characteristics, treatment effectiveness, and factors influencing treatment adherence between physicians and patients with myelodysplastic syndromes

Steensma

Komrokji

Stone

et al. 2014

Cancer

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BACKGROUND: Previous studies have suggested that many patients with myelodysplastic syndromes (MDS) have an incomplete understanding of their disease, which may influence adherence to prescribed regimens and outcomes. METHODS: To better understand physician and patient perceptions about MDS and MDS therapy, the authors conducted 2 surveys in February 2012: 1 for patients with MDS and 1 for health care professionals (HCPs) who cared for patients with MDS. Patient and HCP surveys consisted of 57 and 49 questions, respectively, assessing understanding of MDS, perceptions of specific treatments, barriers to treatment adherence, and treatment experience. RESULTS: In total, 477 complete patient responses and 120 complete HCP responses were received. Among patient responders, 63% were aged 60 years, and 42% had received at least 1 disease-modifying therapy. Of the 61 physician responders, 57% practiced in an academic setting, and 43% practiced in the community; 71% of the 59 nonphysician HCPs worked in the community setting. Only 10% of patients agreed that MDS represented "cancer" compared with 59% of physicians and 46% of nonphysician HCPs (P <.001). Only 29% of patients reported that MDS was ever "curable" compared with 52% of physicians (P <.001). Physicians viewed the potential benefits of active therapy as greater than patients, but patients perceived the actual treatment experience more positively than physicians and differed from physicians in perceived reasons for stopping therapy. CONCLUSIONS: Physicians, nonphysician HCPs, and patients with MDS have disparate views of MDS characteristics and the value and limitations of treatments for MDS. Improved communication and education may increase understanding and achieve better treatment adherence and patient outcomes.

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Cause of death in patients with lower‐risk myelodysplastic syndrome

Cited by 132 publications

References 13 publications

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Myelodysplastic syndromes: 2012 update on diagnosis, risk‐stratification, and management

Randomized Open-Label Phase II Study of Decitabine in Patients With Low- or Intermediate-Risk Myelodysplastic Syndromes

Disparity in perceptions of disease characteristics, treatment effectiveness, and factors influencing treatment adherence between physicians and patients with myelodysplastic syndromes

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