Philadelphia (Ph) chromosome-positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood: natural history and diagnostic differentiation from Ph-negative essential thrombocythemia

Michiels, Jan; Berneman, Zwi; Schroyens, Wilfried; Kutti, Jack; Swolin, Birgitta; Ridell, BÃ¶rje; Fernando, Pagani; Zanetto, Ulises

doi:10.1007/s00277-004-0877-4

Cited by 56 publications

(58 citation statements)

References 34 publications

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“…A recent large international study confirmed the prognostic relevance of distinguishing ET from pre-fibrotic PMF [26]. In the absence of JAK2/CALR/MPL mutations, the possibility of chronic myeloid leukemia (CML) is readily addressed by BCR-ABL1 mutation screening, but it is also to be noted that megakaryocytes in CML (small and hypolobulated) are easily distinguished from those of ET [46] The diagnosis of post-PV or post-ET MF should adhere to criteria recently published by the International Working Group for MPN Research and Treatment (IWG-MRT) (Table III) [47]. …”

Section: Diagnosismentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms, respectively characterized by erythrocytosis and thrombocytosis. Other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: PV is defined by a JAK2 mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely. Differential diagnosis in ET includes reactive thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis. Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) mutations occur in approximately 55%, 25%, and 3% of ET patients, respectively. The same molecular markers are also present in prefibrotic myelofibrosis, which needs to be morphologically distinguished from ET. Survival and leukemic/fibrotic transformation: Median survivals are ∼14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. JAK2/CALR mutational status does not affect survival in ET. Risk factors for survival in ET and PV include advanced age, leukocytosis, and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Thrombosis risk stratification: Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis: high‐risk is defined by the presence of age >60 years or presence of thrombosis history; low‐risk is defined by the absence of both of these two risk factors. Recent data consider JAK2V617F and cardiovascular risk factors as additional risk factors. Presence of extreme thrombocytosis might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk‐adapted therapy: The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. In low risk patients, this is accomplished by the use of low‐dose aspirin and phlebotomy (hematocrit target <45%) in PV. In high risk (for thrombosis) patients, treatment with hydroxyurea is additionally recommended. Treatment with busulfan or interferon‐α is usually effective in hydroxyurea failures and the additional value of JAK inhibitor therapy in such cases is limited. Screening for AvWS is recommended before administrating aspirin, in the presence of extreme thrombocytosis. Am. J. Hematol. 90:163–173, 2015. © 2014 Wiley Periodicals, Inc.

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Section: Diagnosismentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

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“…47 Finally, it has been proposed that cytogenetic analysis should be undertaken in all cases of ET, as rarely CML may present with an identical phenotype. [48][49][50] Although such presentations are rare, the success of tyrosine kinase inhibitors in CML makes it important that such a diagnosis is not missed. 51 Finally, cytogenetic analysis of haematopoietic colonies suggests that, at least in some patients, the disease can arise at the multipotent stem cell level.…”

Section: Essential Thrombocythaemiamentioning

confidence: 99%

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

Reilly

2008

Leukemia

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The frequency of cytogenetic abnormalities in the Philadelphianegative myeloproliferative neoplasms (MPNs) varies from approximately 30% in primary myelofibrosis (PMF) to less than 5% in essential thrombocytosis (ET). The spectrum of aberrations is heterogeneous, ranging from gains and losses of genetic material to structural changes including unbalanced translocations. However, no specific abnormality has been identified to date. Nevertheless, such investigations can provide evidence of clonality and, as a result, cytogenetic findings have been included in the WHO diagnostic criteria for this group of diseases. The aim of the current review is to discuss the pathogenetic insight and prognostic information that standard, as well as molecular cytogenetic analysis has provided. A brief overview is given of the cytogenetic findings in the individual diseases, followed by a more detailed discussion of the possible pathogenetic consequences of specific abnormalities and their impact on prognosis.

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“…The clinical outcome of BCR/ABL positive ET is poor as compared to BRC/ABL-negative thrombocythemia in MPD [14]. The bone marrow in BCR/ABL positive ET is featured by predominant and pronounced mononucleated megakaryopoiesis with initial no, minor or overt granulocytic hypertrophy consistent with CML.MP (Figure 1).…”

Section: Ph-positive Essential Thrombocyhemia (Et)mentioning

confidence: 99%

“…The bone marrow in BCR/ABL positive ET is featured by predominant and pronounced mononucleated megakaryopoiesis with initial no, minor or overt granulocytic hypertrophy consistent with CML.MP (Figure 1). Important differences between BCR/ABLpositive ET and BCR/ABL-positive CML at time of presentation are the predilection of BCR/ABL-positive ET for females and the absence of splenomegaly [14]. Ph-positive ET patients have no features of CML in the peripheral blood at time of presentation.…”

Section: Ph-positive Essential Thrombocyhemia (Et)mentioning

confidence: 99%

“…Michiels et al and the German pathologists Georgii and Thiele recognized that small mono-or bi-nucleated megakaryocytes are diagnostic for the Ph-positive diseases ET and CML. In contrast, large megakaryocytes with hyper-lobulated nuclei are pathognomonic for Ph-negative essential thrombocythemia (Figures 1 and 2) [13][14][15][16][17][18][19][20][21][22][23][24]. The Hannover Bone Marrow Classification of CML and MPD regarded myelofibrosis (MF) as a reactive secondary feature of myeloproliferative disease.…”

Section: The Hannover Bone Marrow Classification Of CML and The Mpds mentioning

confidence: 99%

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Bone Marrow Features and Natural History of BCR/ABL-Positive Thrombocythemia and Chronic Myeloid Leukemia Compared to BCR/ABLNegative Thrombocythemia in Essential Thrombocythemia and Polycythemia Vera

Michiels¹

2015

J Hematol Thrombo Dis

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The Hannover bone marrow (BM) classification distinguished three phenotypes of BCR/ABL-positive CML: CML of common type (CML.CT), CML with megakaryocyte increase (CML.MI) and CML with megakaryocyte predominance (CML.MP). BCR/ABL-positive essential thrombocythemia (Ph-positive ET) is featured by CML.MP bone marrow picture of small monolobulated megakaryocytes and is part of the CML spectrum as a malignant disease (neoplasia) with an obligate transition into acute leukemia of near to 100% after 10 years follow-up. The Hannover BM classification distinguished three primary prefibrotic BCR/ABL-negative (Ph-negative) myeloproiferative disorders (MPD)s: essential thrombocythemia (ET), polycythemia vera (PV) and chronic or primary megakaryocytic granulocytic myeloproliferation (CMGM/PMGM). The incidence of blasts crisis is low in the Phnegative MPDs ET, PV and CMGM. The risk of myelofibrosis is high in CMGM/PMGM, moderate in PV but low in Ph-negative ET. In BCR/ABL-positive thrombocythemia the platelets are small and indolent (non-reactive) and megakaryocytes are smaller than normal with hypolobulated nuclei caused by BCR/ABL induced maturation defect. BCR/ABL-positive thrombocythemia does not present erythromelalgic thrombotic or bleedings manifestations at increased platelet count in excess of 400 to 1500 × 10 9 /L. The platelets and megakaryocytes in BCR/ABL-negative ET and PV are large due to growth advantage caused by constitutively activated by the JAK2V617F or MPL515 mutation. JAK2 and MPL mutated thrombocythemias are associated with a high risk on aspirin responsive plateletmediated inflammation and thrombosis in the end-arterial circulation (platelet thrombophilia).

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Philadelphia (Ph) chromosome-positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood: natural history and diagnostic differentiation from Ph-negative essential thrombocythemia

Cited by 56 publications

References 34 publications

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Pathogenetic insight and prognostic information from standard and molecular cytogenetic studies in the BCR-ABL-negative myeloproliferative neoplasms (MPNs)

Bone Marrow Features and Natural History of BCR/ABL-Positive Thrombocythemia and Chronic Myeloid Leukemia Compared to BCR/ABLNegative Thrombocythemia in Essential Thrombocythemia and Polycythemia Vera

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