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Very young patients with ET and PV
Details of some large cohorts of young patients with MPN, defined sometimes as below 60 and at other times as below 40 years old, have already been published.5-8 Notwithstanding these publications, there are only sparse data concerning very young patients with MPN (aged below 20 years at diagnosis), particularly regarding details such as initial characteristics (reason for consulta- tion, clinical features, bone marrow biopsy features) and outcomes (thrombosis, pregnancy, disease evolution, incidence of second cancer and survival). Furthermore, the utilization of therapeutic modalities in this popula- tion is largely unknown. For example, the proportions of very young patients treated with antiplatelet and/or cytoreductive therapies and the therapeutic goals are very poorly defined and, furthermore, there is no infor- mation about the potential, long-term sequelae of the treatments.
Here we present a review of published cases of ET and PV patients below the age of 20 years at the time of diag- nosis. The earliest data collection point we chose was 2005, coincident with important discoveries concerning the molecular pathogenesis of these conditions, so that we would have more information about the mutational status of the patients and to improve the likelihood of ruling out reactive conditions confounding the diagnosis.9-12 We describe the biological and clinical characteristics at the time of diagnosis and the incidence of vascular and long- term complications during the follow-up.
Methods
PubMed research
The purpose of this review was to learn more about young patients diagnosed with MPN: their characteristics at diagnosis and the incidence of complications. To our knowledge there has been no systematic review of the published cases. We used PubMed (https://www.ncbi.nlm.nih.gov /pubmed) to identify articles related to our topic.
AB
For this review, we analyzed papers referring only to patients with ET or PV who were under 20 years old at the time of the diagnosis. The keywords used during the research were: poly- cythemia vera, primary or essential thrombocythemia/thrombo- cytosis, myelofibrosis, myeloproliferative neoplasms or diseases, young patients/adults, children/childhood and pediatric cases. To avoid the bias of recording misdiagnosed PV cases, only papers published since 2005 were eligible, coincident with the date of the discovery of the JAK2V617F mutation. Furthermore, we directly excluded familial MPN cases, if this was clearly specified in the title or the text. All types of articles were collected: general reviews, cohort papers (including more than 5 patients) and case reports (including fewer than 5 patients).
Selection of the articles
We identified 87 articles concerning MPN and young patients and we finally analyzed 46 articles after exclusion of redundant papers (same authors, same numbers of patients), uninformative cases (no information about diagnosis or outcomes), alternative myeloid diseases (primary myelofibrosis, acute leukemia), inade- quate age identification (cohorts of young patients, but below 40 years old) as delineated in the PRISMA flowchart (Online Supplementary Figure S1) and the checklist (Online Supplementary Table S1).
In total, we identified 46 informative articles: 19 cohort papers
(16onETand3onPV)and27casereports(23onETand11on
PV, with some concerning both conditions).9-56 We also added
seven papers with useful information concerning epidemiolo- gy.57-63
Collected characteristics
All informative articles were printed (published articles and sup- plementary data) and searched data were extracted and reported in an Excel file.
The following data collected at the time of diagnosis were recorded: age, sex, circumstances of diagnosis (e.g. thrombosis), symptoms (hyperviscosity, pain, fatigue, pruritus, microvascular events), full blood count (leukocyte, hemoglobin and platelet lev- els), previous cardiovascular events (thrombosis and hemorrhage),
Figure 1. Driver mutations among very young patients with (A) essential thrombocythemia (n=206) or (B) polycythemia vera (n=55). ET: essential thrombocythemia; PV: polycythemia vera; 3NEG: triple negative for the JAKV617F, CALR and MPL driver mutations. 2NEG: double negative for JAK2V617F and JAK2 exon 12.
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