FRANCESCO PASSAMONTI (VARESE)
MPN RISK STRATIFICATION
Barbara Mora1,2 and Francesco Passamonti1,2
1 Department of Medicine and Surgery, University of Insubria, Varese, Italy
2 Hematology, ASST Sette Laghi, Varese, Italy
In the myeloproliferative neoplasms (MPNs) research setting, the tendency to a personalized
prediction of complications and survival is evident. Grinfeld et al recently analyzed 2035 MPNs
patients using an extensive panel of myeloid genes 1. Such an integrated clinical-molecular
characterization allowed to distinguish eight genomic subgroups, characterized by different
phenotype, risk of evolution into blast phase and probability of events during follow-up 1. In
clinical practice, current predictive scores differ according to MPNs subtype and the addition
of molecular information is expanding the number of available models.
Driver mutational status has implemented the prediction of vascular complications in essential
thrombocythemia (ET) 2-4: the evidence of a higher thrombotic risk in case of JAK2 mutation
led to the development of the International Prognostic Score of thrombosis in Essential
Thrombocythemia (IPSET-t) and its revised version 5,6. On the contrary, current overall
survival (OS) scores in ET and polycythemia vera (PV) consider only clinical-laboratory
parameters (i.e., leukocytosis) 7,8. Besides, the most recent European Leukemia Net (ELN)
guidelines on MPNs do not recommend to routinely use Next Generation Sequencing (NGS)
data in these diseases 2. However, the rapid evolution of knowledge may soon change our
approach: a recent NGS study allowed to integrate genetic and conventional data in order to
define a Mutation-enhanced International Prognostic Scoring System (MIPSS-ET/PV) 9.
According to the latter, mutations in splicing factor genes appear to be independent risk
factors for OS in ET and PV 9. Considering OS in primary (PMF) and secondary myelofibrosis
(SMF), the ELN guidelines suggest using conventional prognostic models, calculated at
diagnosis (International Prognostic Scoring System, IPSS) or during the course (Dynamic-IPSS,
DIPSS; DIPSS-plus) 2,10-12. Nevertheless, these scores have later proven suboptimal in
predicting SMF survival 13,14: using the MYSEC (Myelofibrosis Secondary to Polycythemia
Vera and Essential Thrombocythemia) cohort of 685 SMF with known driver mutational status,
it has been possible to define a clinical-molecular score, the MYSEC-Prognostic Model (MYSEC-PM)
15. Thanks to the MYSEC cohort size, a number of evidences on SMF-specific prognostic
factors aroused: the predictive role of driver mutations 16, chromosomal abnormalities 17,
female gender 18 and bone marrow fibrosis grade 19 has been revealed. NGS has
significantly empowered OS prediction in PMF, and such analysis is suggested if available
2,20. Essential in this sense was the discovery of additional "high molecular-risk" (HMR)
mutations 21: ASXL1, EZH2, IDH1, IDH2, and SRSF2 correlate in fact with reduced OS 21.
Particularly unfavorable is the ASXL1-positive/CALR-negative status 22. These evidences led
to the development of three more prognostic models including molecular data: MIPSS70
(Mutation-enhanced IPSS for transplant-age patients), MIPSS70 plus version 2.0 and the
genetic-only GIPSS (Genetically Inspired Prognostic Scoring System) 23-25.
On the other hand, the role of additional myeloid mutations in SMF is yet to be defined.
Among the HMR genes, the only one that appears to have an unfavorable role is SRSF2, in case
of previous ET 26. In another study, ASXL1 and TP53 were associated with detrimental
prognosis 27. NGS analysis of the MYSEC cohort is currently ongoing (personal
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES