Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia

Patel, Jay P.; Gönen, Mithat; Figueroa, María E.; Fernandez, Hugo F.; Sun, Zhuoxin; Racevskis, Janis; Vlierberghe, Pieter Van; Dolgalev, Igor; Thomas, Sabrena; Aminova, Olga; Huberman, Kety; Cheng, Janice; Viale, Agnès; Socci, Nicholas D.; Heguy, Adriana; Cherry, Athena M.; Vance, Gail H.; Higgins, Rodney R.; Ketterling, Rhett P.; Gallagher, Robert E.; Litzow, Mark R.; Brink, Marcel R.M. van den; Lazarus, Hillard M.; Rowe, Jacob M.; Luger, Selina M.; Ferrando, Adolfo A.; Paietta, Elisabeth; Tallman, Martin S.; Melnick, Ari; Abdel-Wahab, Omar; Levine, Ross L.

doi:10.1056/nejmoa1112304

Cited by 1,746 publications

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“…This inferior prognosis of acute myeloid leukemia ex chronic myelomonocytic leukemia is not explained merely by a higher incidence of adverse karyotype compared with de novo acute myeloid leukemia, but rather appears to be related to an older patient population (treated less intensively when compared with the younger de novo acute myeloid leukemia cohort), absence of the favorable risk acute myeloid leukemia translocations inv (16) 42 The outcome and classification of the subset of acute myeloid leukemia ex chronic myelomonocytic leukemia patients with mutated NPM1, which confers a favorable prognosis in de novo acute myeloid leukemia, warrants further study.…”

Section: Discussionmentioning

confidence: 98%

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

Courville

Kourda

et al. 2013

Modern Pathology

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Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (Po0.01) and less likely to receive aggressive treatment (P ¼ 0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P ¼ 0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.

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Section: Discussionmentioning

confidence: 98%

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

Courville

Kourda

et al. 2013

Modern Pathology

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“…Similarly, regarding the impact on outcome, this research article study showed that KIT mutations did not reach a significative value as independent prognostic factor for relapse and survival neither in the multivariate nor in the Kaplan-Meier analysis, in contrast to those reported in adult patients with t(8;21) (Figs. 1B-2B; Tables III and IV) [24,[26][27][28][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

“…Retrospective studies have demonstrated that the presence of KIT mutations in exon 17 have been associated with a poor outcome in CBF-AML and, for that reason, KIT mutation testing has been recently incorporated into National Cancer Guidelines to better stratify such patients in different prognostic subgroups [25]. However, while several studies showed that activating KIT mutations confer a significantly lower survival in AML with t(8;21)(q22;q22), the negative prognostic impact of KIT mutations in CBFb-AML remains controversial [24,[26][27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Old and new prognostic factors in acute myeloid leukemia with deranged core‐binding factor beta

et al. 2013

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Acute myeloid leukemia (AML) with deranged core‐binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50–70% of patients cured using contemporary treatments. We analyzed the prognostic significance of clinical features on 58 patients with CBFβ‐AML aged ≤60 years. Increasing age was the only predictor for survival (P <0.001), with an optimal cut‐point at 43 years. White blood cells (WBCs) at diagnosis emerged as an independent risk factor for relapse incidence (P = 0.017), with 1.1% increase of hazard for each 1.0 × 109/L WBC increment. KIT mutations lacked prognostic value for survival and showed only a trend for relapse incidence (P = 0.069). Am. J. Hematol. 88:594–600, 2013. © 2013 Wiley Periodicals, Inc.

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“…13,14 Recurrent mutations in IDH, AXL receptor tyrosine kinase (ASXL), DNMT3a, TET2, MLL, and PHF6 have recently been identified, for which the prognostic effect is being actively investigated in combination with previously described cytogenetic and molecular features. [15][16][17] Several groups have attempted to build models incorporating important patient-related and disease-related factors to provide prognostic and predictive systems for patients undergoing intensive chemotherapy. 18 However, to the best of our knowledge, none of these models have integrated nonbiological factors (NBFs) such as employment, education, income, health insurance, and marital status, which may affect how one accesses and interacts with health care and, ultimately, clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

Nonbiological factors affecting survival in younger patients with acute myeloid leukemia

Borate

Mineishi

Costa

2015

Cancer

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BACKGROUNDProgress has been made in determining the biological variants of acute myelogenous leukemia (AML) and their prognostic implications. However, to the authors' knowledge, little is known regarding the impact of nonbiological factors (NBFs) on the survival of patients with AML.METHODSThe impact of NBFs (marital status, insurance status, county‐level income, and education) on survival was assessed along with biological factors (disease subtype, sex, age, and race/ethnicity) using a cohort of patients aged 19 to 64 years who were diagnosed with AML between 2007 and 2011 and reported to the Surveillance, Epidemiology, and End Results program registry (SEER 18).RESULTSThere were 5541 patients included. The median overall survival for the entire study population was 16 months. On multivariate analysis, an increased risk of death was independently linked to being a Medicaid beneficiary, uninsured, single, divorced, and residing in a county within the lower 3 quintiles of median household income. NBFs affected the risk of early (<2 months) and late mortality and their impact was confirmed among patients known to have received chemotherapy.CONCLUSIONSInsurance status, marital status, and county‐level income were found to independently affect the survival of younger patients with AML and should be integrated into outcome comparisons. Interventions are needed to mitigate the impact of social factors on survival among patients with AML. Cancer 2015;121:3877–3884. © 2015 American Cancer Society.

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Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia

Cited by 1,746 publications

References 21 publications

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia

Old and new prognostic factors in acute myeloid leukemia with deranged core‐binding factor beta

Nonbiological factors affecting survival in younger patients with acute myeloid leukemia

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