How to manage children and young adults with myeloproliferative neoplasms

Abstract

On the basis of my personal clinical and research experience and validated by the current literature, my approach to the management of pediatric (age o18 years) and young patients (age o40 years) with classic myeloproliferative neoplasms is presented by focusing on diagnosis, patient communication, risk stratification and therapy. The WHO-2008 diagnostic criteria are recommended, even though in children suspected with essential thrombocythemia (ET), a specific set of diagnostic features may be required. Patient communication includes information on natural history, genetic abnormalities and counseling in all women of child-bearing age. The main challenge in children and young adults with ET and polycythemia vera (PV) is to avoid recurrence of major thrombosis by selecting those patients who ultimately can benefit from cytotoxic and antithrombotic therapy without increasing the incidence of drug-induced side effects. In asymptomatic low-risk patients no therapy is prescribed while in high-risk low-dose aspirin, hydroxyurea and interferon-alpha are my first line drugs. My first decision when considering treatment of a young patient with primary myelofibrosis (PMF) or post-PV or post ET-myelofibrosis, is whether he/she qualifies for bone marrow allotransplantation. In the remaining young PMF patients palliative therapy or experimental drugs are considered.Leukemia ( Keywords: myeloproliferative neoplasms; treatment; young people INTRODUCTION Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are currently classified among the bcr/abl-negative, 'classic' myeloproliferative neoplasms (MPNs) and represent a stem cell-derived clonal myeloproliferation. Hematopoietic progenitors derived from patients with MPNs are hypersensitive to the stimulation of physiological growth factors such as thrombopoietin or erythropoietin (EPO). 1 Since 2005, the pathophysiology of these diseases has advanced considerably with the discovery of an acquired mutation of JAK2 V617F in a vast majority of PV patients and in almost half of those with ET and PMF. 2 The mutation, located within the negative regulatory pseudokinase, or Janus homology 2 domain, causes cytokine-independent activation of several biochemical pathways implicated in EPO receptor signaling. Subsequently, mutations in MPL were reported in B4% of patients with ET or PMF. The significance of JAK2 and MPL mutations for the evolution of the MPNs and their relative roles in determining disease phenotype as well as progression to myelofibrosis and leukemic transformation are unclear at present.In this context, it should be underscored that most of the information in terms of diagnosis, prognosis and therapy focuses on the 'average' MPN patients of whom median age ranges between 60 and 65 years. On the other hand, less consistent data are available in the groups of MPN patients who are presenting below this median age such as pediatric and young adults (20% of MPN patients). This issue is now becoming more and more important, because with the ad...

Primary thrombocytosis in children

“…One report recommends aspirin in young adult patients with erythromelalgia or cardiovascular risk factors. 85 In addition, one study in adults suggested that aspirin should be given twice daily in these patients because of enhanced platelet turnover. …”

“…85 In addition, one study in adults suggested that aspirin should be given twice daily in these patients because of enhanced platelet turnover.…”

“…85 Since there is good evidence for the safety of hydroxyurea in even young children with sickle cell disease, 91,92 is this something that should be considered first line for pediatric patients with ET? And should cytoreductive therapy be considered for children with HT who show more progressive signs of disease?…”

“…He appropriately points out that there is little information on management in children and it is challenging to plan a treatment protocol for children with ET. 85 The European Leukemia Network (ELN) recommended using cytoreductive therapy as a last resort and expressed caution regarding use of aspirin in children under 12 years of age.…”

Cefalea en trombocitosis esencial: reporte de un caso juvenil.

“…La TE con frecuencia se observa entre los 65 a 70 años, con un rango de edad variable, es poco frecuente en menores de 30 años y se presenta predominante en el sexo femenino (1,6,7).…”