MNP Adolescents

Best Practice & Research Clinical Haematology 35 (2022) 101374
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Best Practice & Research Clinical Haematology

journal homepage: www.elsevier.com/locate/issn/15216926
Myeloproliferative neoplasms in adolescents and young adults

Rodothea Amerikanou, Jonathan Lambert, Samah Alimam *
Haematology Department, University College London Hospitals NHS Foundation Trust, London, 250 Euston Road, NW12PG, UK
A R T I C L E I N F O A B S T R A C T
Keywords: Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders commonly diagnosed in the
Myeloproliferative neoplasms seventh decade of life. With increasing access to blood surveillance, the number of adolescent and
Adolescents young adults (AYAs) diagnosed with MPNs is increasing. AYAs represent a unique cohort of MPN
Young adults
patients with differing challenges and psychosocial needs. The majority of AYA patients are fe
Essential thrombocythaemia
Polycythaemia vera
males diagnosed with essential thrombocythaemia and most are asymptomatic at diagnosis.
Myelofibrosis There is a striking predisposition to venous thrombotic events with a significant number expe
Pregnancy riencing splanchnic venous thrombosis (up to 70% of venous events). When compared to older
patients, AYAs appear to have an indolent disease course. Interferon is the preferred cytoreduc
tive agent in this population; indications for commencing treatment mirror those of older adults
and are determined by the presence of high-risk features for thromboembolic events.
1. Introduction
Philadelphia negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders that lead to single or multilineage
myeloid hyperplasia [1]. The classical MPNs, polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis
(PMF), constitute the majority of MPNs with MPN-unclassifiable, chronic neutrophilic leukaemia and chronic eosinophilic leukaemia
being rarer entities [2]. PV characteristically displays trilineage (erythroid, megakaryocytic and granulocytic) proliferation in the bone
marrow with predominantly erythrocytosis in the peripheral blood and commonly suppressed endogenous erythropoietin production
[3,4]. The hallmark of ET is megakaryocyte hyperplasia with resultant thrombocytosis [3]. PMF is characterised by bone marrow
fibrosis with excess collagen fibres and megakaryocyte hyperplasia [5]. The classical MPNs share the increased risk of thromboembolic
events and peril of transformation to acute myeloid leukaemia (AML) [6,7].
Myeloproliferative neoplasms are usually regarded as conditions of older adults with the median age at diagnosis being in the
seventh decade of life, however increasingly they are diagnosed in younger people, whose clinical and molecular features represent a
slightly different group compared to those seen in older adults [8–10]. This review will summarise the characteristics of MPNs in
adolescents and young adults (AYA) and compare to those reported in the broader MPN population.
2. MPN in AYA: clinical presentation and disease features
The AYA population is defined as individuals aged between 15 and 39 years of age and represent 10–20% of MPN diagnoses with an
incidence rate of 0.70/100,000 person-years [9,11,12]. However, over the last two decades, with increasing access to blood moni
toring there has been a rise in MPN AYA diagnosis [13]. The AYA MPNs represent a distinct cohort; ET is the commonest diagnosis with
* Corresponding author.
E-mail addresses: r.amerikanou@nhs.net (R. Amerikanou), jonathanlambert@nhs.net (J. Lambert), s.alimam@nhs.net (S. Alimam).
https://doi.org/10.1016/j.beha.2022.101374
Received 26 July 2022; Received in revised form 5 August 2022; Accepted 11 August 2022
Available online 14 August 2022
1521-6926/© 2022 Elsevier Ltd. All rights reserved.
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R. Amerikanou et al. Best Practice & Research Clinical Haematology 35 (2022) 101374
a female predominance of 60–70% vs 62% in older adults [9,14].

The clinical presentation of AYA MPNs follows a similar reporting pattern to older adults and includes a heterogenous symptom
burden as described in Fig. 1. A large proportion, up to 50% of patients, are asymptomatic [14–16]. The commonest symptom
described in AYA patients is headache and is observed in up to 30% vs 48% in older adults [14,15,17]. Pruritus is present in up to 20%
vs 40% in the older adults, whilst erythromelalgia is observed in a minority of patients (4.7%), which is similar to older adults and
[14–16,18,19]. Splenomegaly is reported in up to 28% of ET and 57% of PV compared to a lower prevalence in older adults (25% in PV
and 14% in ET) [9,10,14,16]. In PMF up to 70% of AYA and older MPN patients present with splenomegaly [9,10]. Bleeding mani
festations are reported in up to 6% of AYA patients and can include gastrointestinal and uterine bleeding, amongst other forms [10,14,
20]. Investigations for acquired bleeding disorders such as von Willebrand disease are recommended in patients with a bleeding
diathesis or extreme thrombocytosis (>1000 × 109/L) to help guide management [6].
Thrombosis may be the presenting feature leading to an MPN diagnosis and is a recognised major cause of morbidity and mortality
in MPNs [21,22]. Arterial events can include myocardial infarction, ischaemic stroke and peripheral arterial thrombosis [22]. Venous
events may present as pulmonary embolism (PE), deep vein thrombosis (DVT) and thrombosis at unusual sites such as splanchnic veins
and cerebral venous sinuses, while microvascular thrombotic events can present as headaches and erythromelalgia [22]. Although the
AYAs are overall a low risk group of patients in view of age and cardiovascular risk, there remains a disproportionately high risk of
thromboembolic events in this population [9,10,14,16,23]. Sobas et al. report a high rate of thromboembolic events in their cohort,
10% after 10 years of follow up [14].
As demonstrated in Fig. 2 over two thirds of thrombosis reported in the AYA occur in the venous system [9,14,20,23]. In AYA
venous thrombosis at presentation is reported in up to 42% of PV patients (vs up to 24% in older adults) and up to 17% in ET (16% in
older adults) [9,16,23]. Arterial thrombosis is less frequent in the AYA; it is observed in up to 20% of PV patients (vs 30% in older
adults) and up to 14% of ET patients (vs 35% in older adults) [9]. There is a striking higher prevalence of splanchnic vein thrombosis
(SVT) in the AYA cohort when compared with older adults; this can be often the first clinical manifestation of MPN in patients [16,24].
SVT constitutes over 75% of venous events reported amongst the AYA compared to 7.5% in the older MPN population with Budd Chiari
syndrome representing over 60% of the events [10,14,15,20,25,26]. Despite specialist management, recurrences of SVT or other
thrombosis may occur in 15–20% of patients [27]. Interestingly, over 15% of SVT patients appear to have a JAK2V617F mutation
without abnormal blood parameters [27]. Pregnancy of course confers a further increase in thrombosis risk. Close monitoring and
tailored management plans should therefore be offered as discussed later [28].
3. Molecular genetics
The discovery of the JAK2V617F mutation changed the landscape of the molecular understanding of MPNs and paved the way for
targeted therapeutic interventions [29]. Fig. 3 outlines the mutational landscape in the AYA population. Mutational frequencies in the
AYA PV cohort mirrors that of the older MPN population, where over 95% of PV patients harbour the JAK2V617F mutation and 2–3%
Fig. 1. Constitutional symptoms commonly reported in the adolescent and young adult population [9,10,14–16,23].
(AP: abdominal pain, BP: bone pain, EM: erythromelalgia).
Fig. 2. Thrombotic events commonly reported in the adolescent and young adult population [9,10,14–16,20,23].
(CVT: cerebral vein thrombosis, DVT: deep vein thrombosis, MI: myocardial infarction, PE: pulmonary embolism, SVT: splanchnic vein thrombosis,
TIA: transient ischaemic attack).
carry mutations in JAK2 exon 12 [6,9,10,14,16,20]. Over 50% of older adult ET is driven by JAK2V617F, 15–24% CALR, and 4% MPL
mutations, which is similarly observed in AYA ET [6,9,14,23]. Triple negative (TN) is a term used to describe patients who lack the
three driver mutations and represents up to 15–20% ETs [6]. In the AYA cohort, TN ET is reported in over 25% [14,15]. With regards to
PMF, as highlighted in Fig. 3c, the majority of AYA patients harbour the CALR mutations, 48% vs 12% in older PMF patients [7,9].
Additionally, 38% carry the JAK2V617F mutation, which is different from older MPN adults in whom JAK2V617F is reported in over
45% of patients [7,9].
Next generation sequencing (NGS) has further highlighted the genetic heterogeneity of the MPNs beyond the driver mutations
described in Fig. 3. Additional somatic mutations, common in myeloid malignancies, are identified in up to a third of MPN patients
[30]. These include mutations in genes which alter DNA methylation (DNMT3A, TET2, IDH1/2), chromatin modification (ASXL1,
EZH2, IDH1/2), messenger RNA splicing (U2AF1, SF3B1, SRSF2, ZRSR2), and DNA repair (TP53) [30]. Patients progressing to sec
ondary myelofibrosis (MF) and AML often exhibit greater genetic complexity with increasing numbers of mutations being detected
along the course of the disease [31]. Mutations such as ASXL1, SRSF2, IDH1/2, and EZH2 in patients with MF can significantly alter the
outcome of the disease and are associated with an increased risk of leukaemic transformation and reduced overall survival [32].
Grinfield et al. note that the number of somatic mutations increase with age, and interestingly, the AYA population appear to have
fewer additional somatic drivers; this may in part explain the better outcome observed in this population [9,33].
Fig. 3. Mutational landscape in the adolescent and young adult population [9,10,14,16,20,23].
(CALR: Calreticulin, JAK2: Janus Kinase 2, MPL: Myeloproliferative Leukaemia).
4. Management
The general approach to investigating and managing AYA MPNs parallels that of the older population. A detailed history, including
family history of MPNs and myeloid disorders, is important in excluding an underlying constitutional predisposition. In our practice,
unless there is very low suspicion for an MPN diagnosis, a bone marrow examination is performed on all new patients as per the World
Health Organisation recommendation. This undergoes a central review with histopathology input in a multidisciplinary team meeting
[34]. In the absence of a mutational driver or if PMF is suspected, a detailed myeloid gene panel is performed; this often aids with
prognostication and diagnosis especially in the triple negative cohort [33].
MPN management is directed primarily at reducing the risk of thromboembolic events and when necessary, managing constitu
tional symptoms [35]. There are currently no validated risk stratification scores for the AYAs, a reflection of the relatively sparse data
available on this population. Therefore, guidance and stratification of the AYAs is extrapolated from recommendations for the older
patients as summarised in Table 1. With regards to antiplatelets, the general consensus is that all patients with a diagnosis of ET or PV
should commence low dose aspirin [6,36–39]. However, there is increasing acceptance that CALR confers a lower thromboembolic
risk; ET patients who are CALR positive and lack other risk factors are therefore considered very low risk and could omit aspirin
prophylaxis [6]. The international community is in agreement that MPN patients aged over 60 years old, or those with a history of
thrombosis or cardiovascular risk factors are considered high risk and therefore warrant initiation of antiplatelet (or anticoagulant
where thrombosis is diagnosed) and venesection (in PV), alongside cytoreductive therapy [6,36–40]. Initiation of cytoreduction
therapy can also occur in the absence of these risk factors when there is extreme thrombocytosis, acquired von Willebrand disease or a
heavy constitutional symptom burden [6,38,39].
There are no agreed protocols for which factors, such as laboratory parameters, thrombosis risk and risk of transformation, should
drive treatment in the AYA. An individualised risk assessment which considers cardiovascular risk factors in addition to arterial and
venous thrombosis history is central to initiating appropriate management. In our practice, low risk ET and PV patients as per Table 1
are managed conservatively with aspirin 75 mg daily (or clopidogrel 75 mg where aspirin is contraindicated) alongside promotion of
lifestyle modifications such as weight loss, blood pressure optimisation and smoking cessation. It is essential to be aware of extreme
thrombocytosis in view of increased risk of bleeding with antiplatelet therapy [6]. All PV patients are enrolled in a venesection
programme with a target haematocrit of less than 45% [6,36,38,39]. Although a haematocrit target of 45% remains the aim as per the
older population, the ideal target haematocrit remains unclear in this population. Additional consideration must be given to the effect
of iron deficiency in the younger AYA population and impact on growth and development [41]. Thus, continuous symptom assessment
Table 1
Summary of current approaches to Polycythaemia Vera and Essential Thrombocythaemia from which management of the adolescent and young adult
is adopted [6,36–39].
(BSH: British Society for Haematology, ELN: European Leukaemia Network, NCCN: National Comprehensive Cancer Network).
Essential Thrombocythaemia Polycythaemia Vera
Risk Group BSH [37] IPSET Revised IPSET Treatment [6,37–39] BSH [36] ELN [38] Treatment [6,36,38,
(ELN) (NCCN) [39] 39]
[38]
Very Low – – • No thrombosis • Observation or – – –
and • Aspirin if
• ≤60 years of cardiovascular risk
age and factors
• JAK2V617F
unmutated
Low • <40 years of 0 • No thrombosis • Aspirin • <65 years of age • ≤60 years • Aspirin and
age and and and of age and • Venesection
• No high risk • ≤60 years of • No history of • No
features age and thrombosis thrombosis
• JAK2V617F
mutation
Intermediate • 40–60 years of 1–2 • No thrombosis • Aspirin • Cardiovascular – • Same as high risk
age and and risk factors or
• No high risk • >60 years of • Platelets >1500 ×
features age and 109/L or
• JAK2V617F • Uncontrolled
unmutated haematocrit despite
venesections or
• High white cell
count
High • >60 years of ≥3 • Thrombosis or • Aspirin (or • >65 years old or • >60 years • Aspirin (or
age or • >60 years of anticoagulation with • Thrombosis of age or anticoagulation with
• Thrombosis or• age and thrombosis history) • thrombosis history
Haemorrhage or • JAK2V617F and Thrombosis and
• Platelet count mutation • Cytoreduction • Cytoreduction
>1500 × 109/L • Adjunct venesection
*IPSET Score: ≥60 years of age = 1, cardiovascular risk factors = 1, previous thrombosis = 2, JAK2V617F = 2.
and blood parameter monitoring is necessary [41]. In patients with known thrombotic events, anticoagulation and cytoreduction
should be initiated [6]. Although vitamin K antagonists (VKA) have traditionally been utilised, recent studies demonstrated direct oral
anticoagulants can be safely used for MPNs [42]. This option can have a positive impact on quality of life, as monitoring VKA can
become an additional and avoidable burden in a group that is often busy with a career and young family commitments.
Cytoreduction is recommended in intermediate and high-risk patients in PV and in high-risk patients in ET (Table 1). Interferon
(IFN) has established efficacy and safety data in younger patients with MPN and is therefore the recommended cytoreductive agent in
this cohort [38]. Additionally, IFN can lead to a decrease in allele burden of both JAK2V617F and CALR. This reduction can be as high
as 90% and in up to 24% of patients leading to a complete molecular response in JAK2V617F [43–45]. This trend has also been
observed in the MF cohort, although modest with 15% of patients demonstrating a 95% reduction in allele burden of JAK2V617F [46].
Interestingly, despite its recommendation for use in the AYA population, a number of studies report low uptake of up to 23% of IFN as
the first line cytoreductive agent when compared to use of hydroxycarbamide (HC) (52%) [10,14–16,47,48]. It is difficult to decipher
if this is due to intolerance or avoidance of use by clinicians due to fear of its side effect profile. IFN is widely known for its heter
ogenous side effect profile, which can include myalgia, mood disturbances, flu like symptoms and liver enzyme derangement [49]. The
Pegylated interferon (Peg IFN) formulation, however, has lower incidence of side effects and is generally better tolerated [50]. In our
practice, unless contraindicated, we propose Peg IFN for all AYA patients, commencing at the lowest dose of 45 μg/week subcuta
neously and increasing according to response and tolerability.
The gold standard agent for cytoreduction in older MPNs remains HC [6,36–38,40]. Although historically there were concerns with
regards to the leukaemogenesis of HC, extrapolating from its use in the sickle population, there is increasing evidence this risk is
negligible, at least in the first two decades [51,52]. Where alternatives are not available or due to intolerances and treatment failures,
HC can be used in the AYA MPN with success. However, patients must be counselled with regards to potential adverse effects on sperm
quality and teratogenicity [52]. Pregnancy should be avoided whilst on HC, and in those in whom pregnancy is planned, HC should be
discontinued at least three months prior to conception [53].
Anagrelide is often employed as the second- or third-line agent where there have been intolerances, poor response or contrain
dications to HC and IFN in ET [54]. It is linked with cardiovascular adverse events and risk of transformation to MF, although the
fibrosis is potentially reversible on cessation [55,56]. Anagrelide is generally well tolerated in the AYA population and can be used
where alternatives are not suitable [10,15,16,48]. However, there should be close monitoring for bone marrow fibrosis [54]. In our
practice, we reserve its use for AYA patients who have failed or are intolerant to HC and Peg IFN. We perform a bone marrow ex
amination prior to initiation of anagrelide therapy and then offer repeat examination every two to three years. We also have a low
threshold for stopping and repeating the bone marrow biopsy where there is suspicion for transformation.
With regards to PMF, age is a core component in the risk stratification; therefore, unsurprisingly the AYA are often classified as low
risk [10]. Like older MPN patients, treatment of PMF centres on constitutional symptom burden management [7]. However, in high
risk patients allogenic stem cell transplant remains the only curative option. Therefore, early identification of such patients and referral
for assessment by bone marrow transplant colleagues is fundamental [7].
Young patients with an MPN can report “a feeling of being given a life sentence” knowing they have a lifelong condition, which
albeit indolent may lead to thromboembolic events and in some transform to AML. This, coupled with the constitutional symptoms
burden whilst trying to maintain a career, social and family life, can become overwhelming. Where possible, we recommend a holistic
approach; attention should be paid to establishing a link with a clinical nurse specialist and referral to a psychologist, in particular one
who has experience with the AYA population. This, in conjunction with exercise therapy such as yoga or access to a fatigue service
where available, have shown great success in manging this complex cohort of patients [57,58]. Additionally, the emerging role of
technology via the use of wellness mobile apps in improving quality of life and MPN symptom burden has recently been demonstrated,
and it may become a useful tool in the AYA [59]. This multifaceted approach is especially relevant where patients and clinicians are
eager to delay initiation of cytoreductive therapy for symptom control.
5. Disease progression
Until recently, there was little literature available on the AYA cohort; although signals from publications in 1980–90s suggested
AYA MPN were of low incidence with overall “good” long term outcomes [60,61]. Despite having gained greater understanding of the
pathogenesis of the MPNs over the last two decades, halting progression to MF and AML has not been achieved. Transformation to MF
in the AYA population is reported in over 20% of PV patients and 15% of ET patients [9,10,14,16,20,23,48]. Szuber et al. speculate
these high rates of progression are in part driven by the longer survival in the AYA compared to older adults [9]. To date, there are no
pharmacological interventions available that can halt progression.
Transformation to AML can occur in up to 25% of all MPN patients with the highest rates in the MF cohort [62]. In the AYA,
progression to AML occurs in up to 2% of ET (vs up to 4% in older adults), 4% of PV (similar to older adults) and up to 10% of PMF (9%
in older adults) [9,10,14,20,23,48]. Even though leukaemic transformation rates do not appear to differ significantly in frequency in
AYA vs older patients, the median duration to transformation is longer in younger patients when compared with older patients (19–20
vs 7–8 years) [10]. Thus, a pillar of MPN management is to identify PMF patients who have the highest risk of transformation to AML
and refer for upfront allogeneic haemopoietic transplant where appropriate [7].
The AYA MPNs appear to have a more indolent course with median overall survival (OS) in ET and PV of over 35 years compared to
up to 22 years in older adults [9,10,14]. Median OS in PMF is over 20 years in AYA versus a much shorter OS of 3–8 years in older
adults from time of diagnosis [9,10]. Although this is promising, it is important to be cautious in interpreting this, as it may in fact not
always be a true reflection of “good overall survival” in view of the young age at diagnosis of the AYA.
6. Pregnancy
With the rise in maternal age in the western world, there are increasing encounters of pregnancies in the MPN population [63].
Although the true incidences of MPN pregnancies remains unclear, in the large Mayo Clinic series over 50% of the AYA cohort were
women with ET [9]. Therefore, it is not surprising that the majority of literature on MPN pregnancies is available in the ET cohort.
Pregnancy in the MPNs can result in foetal and maternal complications, with live births rates as low as 40% (rate 40–70%) compared
with 80% in the general population [28,64,65]. Therefore, pregnancy requires coordination between haematologists, obstetricians,
and other care providers involved in the pregnancy pathway. There needs to be honest and open preconception discussion with regards
to the risks associated with pregnancy and an agreed management plan especially in the high-risk patient.
There is no evidence MPN pathogenesis impacts on fertility outside the iatrogenic effects of cytoreductive agents. For example, HC
is associated with reduced and arrested spermatogenesis in animal models at high doses whilst interferon can lead to a reduced sexual
drive and impaired spermatogenesis [66–69]. However, MPN pregnancies are associated with adverse maternal and foetal outcomes
due to higher risks of maternal thrombosis, haemorrhage and placental dysfunction resulting in foetal growth restriction, early and late
pregnancy losses [63,64]. In the MPN populations, foetal losses can be as high as 30% with the majority of losses occurring in the first
trimester [28]. Maternal complications such as pre-eclampsia are reported in up to 10% of women [63]. Furthermore, over 20% of
newborns are below the 10th centile and there is an increased incidence of premature delivery related to placental insufficiency [63,
70].
In our practice, we consider high risk pregnancies in women who have the any of the following criteria: sustained thrombocytosis
>1500 × 109/L, previous history of venous or arterial thrombosis, haemorrhage secondary to underlying MPN, pregnancy related
complications, unexplained intrauterine growth restriction, three or more consecutive unexplained early miscarriages and abnormal
uterine artery dopplers at 20 weeks [65,71]. Although molecular drivers are not currently considered in risk stratifying MPN preg
nancies, Rumi et al. note a correlation between the JAK2V617F mutation and higher frequency of foetal losses, whilst the CALR
mutation was associated with a better pregnancy course [72]. However, Rumi et al. highlight that overall, the mutational driver did not
appear to predict maternal outcomes [72].
Many studies have explored the benefit of aspirin in improving outcomes in the MPN pregnancies. In our practice, unless con
traindicated, the majority of women are offered aspirin 75 mg daily throughout pregnancy and continued thereafter [28,63,71]. It
remains important to monitor for acquired von Willebrand disease and bleeding especially in extreme thrombocytosis. In the PV
cohort, in addition to aspirin, venesections are continued to maintain a haematocrit within a gestational age-appropriate target [28,
63]. In all patients we encourage regular monitoring with intrauterine artery doppler at 20 weeks, serial growth scans alongside
stringent observations for maternal complications such as pre-eclampsia [71].
Cytoreductive therapy is indicated in high-risk pregnancies. It is widely accepted that IFN (including Peg IFN) is the recommended
agent in women of childbearing age and is safe to use preconception, in pregnancy and during breast feeding [73,74]. Griesshammer
et al. report pregnancy success rates with interferon as high as 94% [75]. Low molecular weight heparin is employed alongside
cytoreductive therapy where there is a history of venous thrombosis (and no contraindication to its use) [28,63]. In our centre, where
possible, initiation of cytoreduction begins at preconception, with 45 μg of Peg IFN weekly (escalating according to response and
tolerability). Although there are reports of successful pregnancies on HC, its use is contraindicated in pregnancy due to teratogenicity
[75]. Anagrelide is associated with disrupted implantation in high doses in mice models and in human studies; furthermore, it can cross
the placenta and cause thrombocytopenia, and is therefore also contraindicated [75,76]. There is little published data on ruxolitinib in
pregnancy and for that reason its use is not recommended.
Over the last decade a number of groups have described pregnancy outcomes and there is an overall consensus that the majority of
MPN pregnancies can end successfully. Management is individualised based on risks of thrombosis and where possible discussions
should begin in the preconception period [71]. In our practice, we lean on the expertise of an obstetric haematologist working closely
alongside obstetricians, midwives and psychologists in managing the patient’s journey and complications should they arise. There is a
strong link with increased monitoring of blood parameters, growth scans and diligent observation for potential obstetric complication.
7. Summary
There is increasing recognition of MPNs in the AYA population and to date there does not appear to be a difference in disease
pathogenesis when compared to older adults. However, the AYA comprise a different disease subset from older adults, with a lower risk
mutational profile [9,10]. In line with the older adults, the main goal of therapy is prevention of thromboembolic events and
recognition of transformation. However, in the AYA community, this needs to be coupled closely with a holistic approach that ad
dresses the psychological wellbeing of the individual. Encouraging the adoption of a healthy lifestyle including regular exercise and a
balanced diet can also help with symptom management and reducing cardiovascular risk [58,77]. If cytoreduction is necessary, we
recommend Peg IFN. In addition, a multidisciplinary approach to AYA patients, especially in pregnancy, is fundamental.
Although the last decade has seen growing interest in AYA MPNs, there remains an unmet need to establish an international global
prospective cohort of AYA patients with long follow up in order to uncover complications and long term outcomes. Greater under
standing of the pathogenesis in the AYA and developing age specific risk stratification is required to aid in identifying patients at high
risk of thrombosis and transformation events in addition to guiding therapies.
Practice points
• There is increasing recognition of MPNs in the AYA population. Although there is no international guidance on managing AYA
patients, current risk stratification and management is extrapolated from older adults and focuses on reducing thromboembolic
events.
• Where cytoreduction is required, interferon, including pegylated interferon, is the recommended first line of therapy in the AYAs.
Additionally, interferon is safe for use prior to conception, during pregnancy and in breastfeeding.
• Pregnancy requires good coordination between haematologists and the obstetric team. Where feasible, discussion should begin
prior to conception.
Research agenda
• International consensus for the diagnosis, risk stratification and management of MPNs in the AYA population.
• Longitudinal studies to gain greater understanding of the pathogenesis of MPNs in the AYAs and establish rates of disease pro
gression and transformation.
• Greater understanding of the pathogenic drivers for the higher rates of splanchnic vein thrombosis amongst AYAs.
Declaration of competing interest
RA, JL and SA declare no conflicts of interest.
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MNP Adolescents

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Best Practice & Research Clinical Haematology 35 (2022) 101374

Contents lists available at ScienceDirect

Best Practice & Research Clinical Haematology

Myeloproliferative neoplasms in adolescents and young adults

2. MPN in AYA: clinical presentation and disease features

a female predominance of 60–70% vs 62% in older adults [9,14].

Declaration of competing interest

RA, JL and SA declare no conflicts of interest.

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