Clonal Megakaryocyte Dysplasia with Normal Blood Values Is a Distinct Myeloproliferative Neoplasm

Abstract

<b><i>Introduction:</i></b> In 1991, we reported 18 persons with a clinical-pathologic entity and termed atypical myeloproliferative disorder because they did not meet the contemporary diagnostic criteria for a myeloproliferative neoplasm. We sought to gain further knowledge on this disease entity. <b><i>Methods:</i></b> This retrospective cohort study included consecutive subjects registered in the database of the Center for the Study of Myelofibrosis in Pavia, Italy, from 1998 to 2020 (June), and diagnosed with atypical myeloproliferative disorder according to our adjudicated criteria. We studied clinical, histological, cytogenetic, and molecular covariates and risks of thrombosis, disease progression, and death. Data were compared with those of concurrent subjects with prefibrotic myelofibrosis. <b><i>Results:</i></b> Fifteen new subjects with atypical myeloproliferative disorder were identified. Seven were male. Median age was 50 years (IQR, 41–54 years). Thirteen were diagnosed with a synchronous symptomatic or incidentally detected thrombotic event. The bone marrow showed megakaryocyte hyperplasia with dysplasia. <i>JAK2</i>V617F was present in 10 subjects and <i>CALR</i> mutation in one. No other somatic mutations were identified in next generation sequencing. After a median follow-up of 101 months (IQR, 40–160 months), no subject had disease progression or blast transformation. Incidence of post-diagnosis or recurrent thrombosis was 3.9 events (95% confidence interval, 3.5–4.0) and 5.0 events (4.6–5.6) per 100 person-years. Features of subjects with atypical myeloproliferative disorder differed markedly from those of 546 subjects with prefibrotic myelofibrosis. <b><i>Conclusion:</i></b> Our data indicate that these 15 persons have a distinct myeloproliferative neoplasm. We propose naming this new disorder clonal megakaryocyte dysplasia with normal blood values.

Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype

“…923 of 1,319 consecutive subjects in our MPNs dataset, as of July 2021, were classified as PMF (402, pre-MF; 521, overt-MF), 41 ET, 40 polycythemia vera, and 165 as MPN, unclassifiable according to the 2016 WHO criteria [1]. Within the MPN, unclassifiable cohort, we re-classified 21 subjects as clonal megakaryocyte dysplasia with normal blood values as recently described [19]. 139 subjects (84%) met our adjudicated criteria for CMD-IT.…”

Myeloproliferative neoplasms and splanchnic vein thrombosis: Contemporary diagnostic and therapeutic strategies

“…4,36 Thus, some authors have considered new names for these situations, such as "latent MPN" or "clonal megakaryocyte dysplasia with normal blood values". 37 The pertinence of such a classification remains to be demonstrated, but it should be emphasized that a large proportion of patients can be diagnosed with one of the classical MPNs by strictly applying the international diagnostic criteria. 9,15,38,39 In fact, once a somatic mutation is identified, BMB analysis or proof of an elevated RBCM usually provides the remaining component to complete the full set of diagnostic criteria.…”

Myelofibrosis-type megakaryocyte dysplasia (MTMD) as a distinct category of BCR::ABL-negative myeloproliferative neoplasms. Challenges and perspectives

“…We recently described two new disease variants we claimed belonging to the BCR::ABL-negative myeloproliferative neoplasms (MPNs) domain [1,2]. The first is a re-formatting of our 1991 article reporting 18 cases of an atypical myeloproliferative disorder with high risk of thrombosis and slow disease progression [3].…”