1. Tiziano Barbui MD Ospedale Papa Giovanni XXIII Bergamo, Italy
Emerging JAK Inhibitors in Myelofibrosis: Determining the Right Agent for the Right Patient.(Madrid) How to use prognosis assessment criteria for MF management in the clinical practice
Tiziano Barbui MD
Ospedale Papa Giovanni XXIII
Bergamo, Italy

3. FROM PV and ET to MYELOFIBROSIS:
The value of bone marrow morphology

4. Bone marrow fibrosis (reticulin=>1): Yes: 74 pts ( 14%)
INITIAL BONE MARROW RETICULIN FIBROSIS IN POLYCYTHEMIA VERA EXERTS AN IMPACT ON CLINICAL OUTCOME (IWG-RT study)
Tiziano Barbui1† , Jürgen Thiele,2† Francesco Passamonti,3 Elisa Rumi,4 Emanuela Boveri,4 Maria Luigia Randi,5 Irene Bertozzi,5 Filippo Marino,5 Alessandro M. Vannucchi,6 Elisabetta Antonioli,6 Valentina Carrai,6 Heinz Gisslinger,7 Veronika Buxhofer-Ausch,7 Leonhard Müllauer,8 Guido Finazzi,1 Alessandra Carobbio,1 Andrea Gianatti,1 Marco Ruggeri,9 Francesco Rodeghiero,9 Emanuele D’Amore,9 Alessandro Rambaldi,1 and Ayalew Tefferi,10 †
526 patients with strictly defined WHO diagnosis of PV Reviewer: JuergenThiele ;Participant centers (Bergamo, Pavia, Padova, Vicenza, Firenze, Vienna)
Follow-up, years 5.3 (0-29.8)
Bone marrow fibrosis (reticulin=>1):
Yes: 74 pts ( 14%)
No: 452 pts (86%)

5. Overt myelofibrosis-free survival (35 events)
BM fibrosis % pts-yr No BM fibrosis % pts-yr
IRR = 2.7, p=0.01
Barbui T et al, Blood 2012

6. Degree of bone marrow fibrosis to predict events in PVSG-ET
N= 361 patients
Fibrosis grade (0 to 4)
# grade 0-1: 135
# grade 2: 146
# grade 3-4: 80
Bone marrow fibrosis at diagnosis predicts
Campbell et al, JCO 2009

7. WHO-ET vs PMF: Prognostic Value

8. Incidence of AML OS Incidence of MF
Survival, Leukemic Transformation and Fibrotic Progression in Essential Thrombocythemia are significantly influenced by Accurate Morphologic Diagnosis
Incidence of AML OS
Incidence of MF
Barbui et al, Leukemia 2013
Barbui et al, J Clin Oncol Aug 10;29(23):

10. CLINICAL OVERT MYELOFIBROSIS:
How to stratify patients to select therapy

11. Improving Survival Trends in PMF
Median survival: 4.6 versus 6.5 y
Cervantes et al. JCO 2012

12. Causes of Death in PMF 13% 4% 5% 10% 14% 19% 31%
Cervantes F et al. Blood 2009;113:
31%
19%
14%
10% 5% 4%
13%

14. Current risk stratification in PMF
Low risk
No factor
IPSS
Intermediate-1 risk score 1
Age > 60 years
Hb <10 g/dL
WBC >25 x109/L
Blasts ≥1%
Constit. symptoms
Intermediate-2 risk score 2
High risk score ≥ 3

15. International Prognostic Scoring System to predict survival (IPSS)
135 months
22%
95 months
29%
48 months
28%
27 months
21%
Cervantes et al, Blood 2008

17. DINAMIC IPSS (DIPSS)

18. HEPATO-SPLENOMEGALY
is not included in the risk
classification of MF

21. CLINICAL OVERT MYELOFIBROSIS:
Predictors of blast phase

23. Myelofibrosis: Prognosis assessment in clinical practice
PMF risk stratification is based on IPSS and DIPSS, but cytogenetics and transfusional status may be a compendium
Novel prognostic variables deserve further investigations on a large scale