Myeloproliferative neoplasms: Morphology and clinical practice

Barbui, Tiziano; Thiele, Jürgen; Vannucchi, Alessandro M.; Tefferi, Ayalew

doi:10.1002/ajh.24288

Cited by 46 publications

(34 citation statements)

References 69 publications

(112 reference statements)

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“…This particular observation might be linked to a higher contamination of MPL-mutated patients with ET by inadvertently included cases of prefibrotic PMF [21]. Of note, a similar observation was seen in ET patients from Mayo Clinic-Italian collaborative study [6] but no difference between mutational categories was seen in risk of post-ET myelofibrosis on a smaller cohort of ET patients by Rotunno et al [12].…”

Section: Discussionmentioning

confidence: 73%

Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia

et al. 2016

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About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining (~15%) are wild type for all three mutations and are referred to as being "triple negative." Furthermore, CALR mutations in ET are structurally classified as type 1/type 1-like or type 2/type 2-like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis-free (MFFS), thrombosis-free, and leukemia-free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple-negative. Among the 109 CALR-mutated cases, 52% were classified as type 1/type 1-like and 48% as type 2/type 2-like. In univariate analysis, triple-negative patients displayed the best and MPL mutated the worst OS (P 5 0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P 5 0.5). LFS was also similar among the different mutational groups (P 5 0.6) whereas MFFS was significantly shorter in MPLmutated patients on both univariate and multivariable analyses (age-adjusted P 5 0.02; HR 7.9, 95% CI 2.0-31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P 5 0.02; HR 1.9, 95% CI 1.1-3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis.

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Section: Discussionmentioning

confidence: 73%

Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia

et al. 2016

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“…Polycythemia vera (PV) is possibly underdiagnosed using the hemoglobin levels published in the fourth edition, and the utility of BM morphology as a reproducible criterion for the diagnosis of PV is recognized. 8,10,11 4. It is necessary to differentiate "true" essential thrombocythemia (ET) from prefibrotic/early primary myelofibrosis (prePMF) by, among other features, the morphologic findings in the BM biopsy, including the lack of reticulin fibrosis at onset, and this distinction has prognostic implications.…”

Section: Myeloproliferative Neoplasms (Mpn)mentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

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The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

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“…[11][12][13][14] Standard procedures were followed for driver mutation screening. The study population was recruited from a consecutive cohort of adult patients (age ≥ 18 years) with MPN seen at the Mayo Clinic from October 27, 1967 through December 29, 2017.…”

Section: Methodsmentioning

confidence: 99%

“…All MPN diagnoses, as well as determinations of fibrotic and/or leukemic transformations, were in strict accordance with the 2008 World Health Organization (WHO) criteria, with special attention to the distinction between ET and prefibrotic MF or masked PV. [11][12][13][14] Standard procedures were followed for driver mutation screening. 15 April 2018 and data collected via medical records or in certain cases, by directly contacting patients or their physicians.…”

Section: Methodsmentioning

confidence: 99%

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

et al. 2018

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First‐line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second‐line drugs of choice include pegylated interferon‐α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928‐1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis‐free (MFFS) and thrombosis‐free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1‐1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7‐6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.

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Myeloproliferative neoplasms: Morphology and clinical practice

Cited by 46 publications

References 69 publications

Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia

Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

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