Allogeneic transplants for myelofibrosis: Ideal induction and timing. Dr. Borje Andersson

1. 2015/5/18 B.S. Andersson
Allogeneic Transplants
for Myelofibrosis: Ideal
Induction and Timing
Borje S. Andersson, MD,
Ph.D.
Mol. Pharmacology and Translat.
Drug Development Program,
Dept Stem Cell Transplantation
UT MD Anderson Cancer Center
January 31, 2015.

2. 5/18/2015 B.S. Andersson
IV Busulfan, Primary Collaborators
UT MD Anderson
Clinical:
RE Champlin EJ Shpall
R Jones Y Nieto
U Popat
Biostatistics:
PF Thall
U Alberta, Calgary, AB, CA:
J Russell
Hopital St Antoine, Paris, France:
M Mohty
Institute Paoli-Calmette, Marseille, France:
D Blaise

3. Myelofibrosis: The Problem
• Heterogeneous Disease
◦ Primary MF vs PCV-MF vs MDS with 2° MF
• ≥20% transformation to AML within 10 years
• Subgroups identified that have vastly divergent prognosis
based on
• Platelet count
• Degree of fibrosis
• Blasts
• Peripheral blood CD 34+-cells
• Constitutional symptoms
• Cytogenetics (except 13q- or 20q-)/complex and
monosomy -5 and -7
• Transfusion requirements

4. Myelofibrosis: Prognosis
Dupriez et al. Blood 1996; 88 (3): 1013
•One point each for
•Hb < 10 gm% and
•WC < 4 or WC > 30
•Low risk: score 0
•Int risk: score 1
•High risk: score 2
OS >96 months
OS 13 months
OS 26 months

5. Mesa et al, Blood 2005.
N=91
Prognosis After Leukemic Transformation

6. Gupta et al BBMT 2014
MF and Allo-SCT, CIBMTR, 2014

7. Gupta et al BBMT 2014
MF and Allo-SCT, CIBMTR, 2014

8. Allogeneic Transplant for Myelofibrosis
Deeg et al: Blood, 2003; 102: 3912-3918
N=21N=56
OS=58%

9. Bu/flu/ATG Mini Protocol: Low Bu (n=15)
• Fludarabine 40mg/m² X 4
• Busulfan 130mg/m² X 2
• ATG 2.5 mg/kg X 3 (for unrelated donors)
• FK/mini methotrexate (day 1,3,6, 11)
• Because of high relapse rate in first 15 patients dose of
Bu was increased

10. Outcome (N=26)
0 200 400 600 800 1000 1200 1400 1600
Days
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Overall Survival 71% (SE 10%)
Median Follow up 21 months (1-43 months)
Event Free Survival 46% (SE 11%)
Popat et al ASH 2009

11. Outcome EFS (N=26)
Popat et al ASH 2009
0 200 400 600 800 1000 1200 1400 1600
Time
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Low dose Bu
High dose Bu

12. What happens to splenomegaly post
transplant?
Aka do we need to perform splenectomy
(TRM?) or XRT to spleen (short-lived
benefit and high-risk?)

13. Pre
24 months
Not palpable

14. What about:
- donor lymphocyte infusion ?
- JAK2 inhibitors ?
- HDAC-inhibitors ?

15. Conclusions
• Allogeneic transplant is effective and only
potentially curative treatment of myelofibrosis.
• Intensity of conditioning regimen is important.
• Systematically controlled conditioning therapy
optimizes outcome.
• Fibrosis and splenomegaly resolve slowly.
• DLI, JAK2-inhibitors, HDAC-inhibitors may be
effective adjuncts for high-risk- and/or recurrent
disease patients, in investigational protocols only.

16. Conclusions (Cont’
• Transplant should be considered early in patients
at high risk for
 a) progression to AML,
 b) high tansfusion requirements, and
 c) without significant comorbidity.
• INFORM, INFORM, INFORM !!