JAK2 INHIBITORS AND ALLOGRAFTING

Andrea Bacigalupo, Genova, Italy

Significant reducti

on of

spleen size w

ith ru

xoliti

nib

Significant survival

advantage for ru

xoliti

nib

survival advantage is

superior w

ith

greater spleen siz

e reducti

on

Thus spleen siz

e = progression

Reduction of sp

leen size = co

ntrol o

f

progression

Reduction of tu

mour masss

?

results of allogeneic hemopoietic stem cell transplants (HSCT) are dependent on disease phase

# DIPSS# Spleen size, transfusion requirement

results of allogeneic hemopoietic stem cell transplants (HSCT) are dependent on disease phase

# DIPSS# Spleen size, transfusion requirement

0,000

0,250

0,500

0,750

1,000

0,0 2000,0 4000,0 6000,0 8000,0

days from transplant

surv

iva

l

Spleen >22 cm; n=31

Spleen <22 cm; n=29

P=0.0008

23%

68%

SPLEEN SIZE AND SURVIVAL in 70 allografted MF (GE SM)

0,000

0,250

0,500

0,750

1,000

0,0 666,7 1333,3 2000,0 2666,7 3333,3 4000,0

Survival Plot

C68

Su

rviv

al

CD34 <8 /cmm n=13

24%

66%

CD34 PB cell counts and SURVIVAL in 70 allografted MF (GE SM)

CD34 9-486/cmm n=30

CD34 >486/cmm n=15

38%

Days from transplant

30

57

86

0102030405060708090

100

<8 9-484 >484

% o

f pts

with

sple

en >

22

cmSpleen size and CD34 cell count

P=0.01

CD34 cell counts

Patients with a large spleen have advanced disease

Survival after allogeneic transplant is worse in patients with a large spleen

Survival after allogeneic transplant is also worse in patients with high CD34 counts

High CD34 counts correlate with large spleen

JAK2 inhibitors can reduce spleen size

JAK2 inhibitors are good candidates for treatment BEFORE an allogeneic transplant

Also AFTER an allogeneic transplant

Cervantes et al Blood 2009; 113: 2895: IPSS

Low = 5% /year

Int-1 = 6.7% /year

Death rate

Int-2 = 8.3% /year

High = 25% /year

Good outcome after S

CT

Poor outco

me after SCT

Good outcome after S

CT

Riulitinib

Reduction of tu

mour

mass

Improved outco

me after

SCT ??

Conclusion

SCT transplant outcome is dependent on disease phase

Ruxolitinib may improve SCT outcome for patients with advanced disease