JAK2 INHIBITORS AND ALLOGRAFTING Andrea Bacigalupo, Genova, Italy

Significant reduction of spleen size with ruxolitinib

Significant survival advantage for ruxolitinib

Thus spleen size = progression Reduction of spleen size = control of progression Reduction of tumour masss? survival advantage is superior with greater spleen size reduction

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

SPLEEN SIZE AND SURVIVAL in 70 allografted MF (GE SM) Spleen <22 cm; n=29 68% 23% Spleen >22 cm; n=31 P=0.0008

CD34 PB cell counts and SURVIVAL in 70 allografted MF (GE SM) CD34 <8 /cmm n=13 66% CD34 9-486/cmm n=30 38% 24% CD34 >486/cmm n=15 Days from transplant

Spleen size and CD34 cell count 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

Death rate Low = 5% /year Int-1 = 6.7% /year Int-2 = 8.3% /year Cervantes et al Blood 2009; 113: 2895: IPSS Death rate Low = 5% /year Int-1 = 6.7% /year Int-2 = 8.3% /year High = 25% /year

Good outcome after SCT Poor outcome after SCT

Reduction of tumour mass Riulitinib Improved outcome after SCT ?? Good outcome after SCT

Conclusion SCT transplant outcome is dependent on disease phase Ruxolitinib may improve SCT outcome for patients with advanced disease