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. 2017 Oct 6;8(60):101735-101744.
doi: 10.18632/oncotarget.21594. eCollection 2017 Nov 24.

Clinical course and outcome of essential thrombocythemia and prefibrotic myelofibrosis according to the revised WHO 2016 diagnostic criteria

Elisa Rumi  1   2 , Emanuela Boveri  3 , Marta Bellini  1 , Daniela Pietra  2 , Virginia V Ferretti  1 , Emanuela Sant'Antonio  4 , Chiara Cavalloni  1   2 , Ilaria C Casetti  1 , Elisa Roncoroni  2 , Michele Ciboddo  1 , Pietro Benvenuti  1 , Benedetta Landini  2 , Elena Fugazza  2 , Daniela Troletti  2 , Cesare Astori  2 , Mario Cazzola  1   2 ; Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators
Affiliations

Clinical course and outcome of essential thrombocythemia and prefibrotic myelofibrosis according to the revised WHO 2016 diagnostic criteria

Elisa Rumi et al. Oncotarget. .

Abstract

The recently revised World Health Organization (WHO) classification of myeloid neoplasms recognizes prefibrotic myelofibrosis (prePMF) as a distinct entity, characterized by well-defined histopathologic features together with minor clinical criteria (leukocytes, anemia, increased LDH, splenomegaly). The aim of the study was to examine the clinical relevance of distinguishing prePMF from essential thrombocythemia (ET). We identified in our database all patients affected with ET, prePMF and primary myelofibrosis (PMF) diagnosed according to 2008 WHO criteria with a bone marrow fibrosis grade 0-1 at diagnosis and one DNA sample to define the mutational status. The bone marrow morphology of all 404 identified patients was reviewed by an expert pathologist and patients were reclassified according to the 2016 WHO criteria. After reclassification, our cohort included 269 ET, 109 prePMF, and 26 myeloproliferative neoplasm unclassificable. In comparison with ET, patients with prePMF had higher leukocyte count, lower hemoglobin level, higher platelet count, higher LDH values, and higher number of circulating CD34-positive cells; they showed more frequently splenomegaly (all P values < ·001). CALR mutations were more frequent in prePMF than in ET (35·8% vs 17·8%, P < ·001). PrePMF patients had shorter overall survival (P < ·001) and a trend to a higher incidence of leukemic evolution (P ·067) compared to ET patients, while they did not differ in terms of thrombotic and bleeding complications. In conclusion, ET and prePMF diagnosed according to 2016 WHO criteria are two entities with a different clinical phenotype at diagnosis and a different clinical outcome.

Keywords: WHO; diagnostic criteria; myelofibrosis; prefibrotic; thrombocythemia.

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Conflict of interest statement

CONFLICTS OF INTEREST Authors do not have competing financial interests.

Figures

Figure 1
Figure 1. Main hematologic parameters in patients with essential thrombocythemia and prefibrotic myelofibrosis diagnosed according to the new 2016 WHO criteria
Data are shown in a box plot depicting the upper and lower adjacent values (highest and lowest horizontal line, respectively), upper and lower quartile with median value (box), and outside values (dots). The figure shows (A) leukocyte count (WBC), (B) hemoglobin (Hb), (C) platelet count (PLT), (D) lactate dehydrogenase level (LDH), (E) circulating CD34-positive cells, (F) the percentage of patients with splenomegaly.
Figure 2
Figure 2. Overall survival of patients with essential thrombocythemia and prefibrotic myelofibrosis diagnosed according to the new 2016 WHO criteria
ET patients had a better overall survival than prePMF patients (overall survival at 10-years 96·6% vs 86·4%, P <·001).
Figure 3
Figure 3. Cumulative incidence of leukemic evolution in patients with essential thrombocythemia and prefibrotic myelofibrosis diagnosed according to the new 2016 WHO criteria
The 10-years cumulative incidence of leukemia was 2·3% (95% CI: 0·4-7·3%) in prePMF and 1·9% (95% CI: 0·4-6%) in ET, with a trend (P ·067) to a higher risk of leukemic evolution in prePMF.
Figure 4
Figure 4. Cumulative incidence of myelofibrotic evolution in the subgroups of 358 patients affected with “old” ET reclassified according to the new 2016 WHO criteria
The cumulative incidence of overt myelofibrosis at 10 years was significantly higher in the “old” ET reclassified as prePMF than in the “old” ET reclassified as ET (9·7% vs 0%, P ·033).
See this image and copyright information in PMC

References

    1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405. - PubMed
    1. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100:2292–2302. - PubMed
    1. Wilkins BS, Erber WN, Bareford D, Buck G, Wheatley K, East CL, Paul B, Harrison CN, Green AR, Campbell PJ. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood. 2008;111:60–70. - PubMed
    1. Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, Rodeghiero F, d’Amore ES, Randi ML, Bertozzi I, Marino F, Vannucchi AM, Antonioli E, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29:3179–3184. - PubMed
    1. Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Vannucchi AM, Antonioli E, Gisslinger H, Buxhofer-Ausch V, et al. Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria. Leukemia. 2012;26:716–719. - PubMed