1. MYELODYSPLASTIC SYNDROME: prognosis & treatment options
JILL Fulcher MD PhD FRCP(UK)
13th oct 2018

2. Normal blood smear 1. Red cells - Contain Hb Anemia when low
2. White cells
- neutrophils
- Infection when low
3. Platelets
Clot formation
Bleeding when low

3. Normal hematopoiesis Blood cells are made in the bone marrow
Hematopoietic stem cell (HSC)
Undergo a series of developmental steps resulting in mature red cells, neutrophils and platelets
Released into bloodstream

4. Myelodysplastic syndrome
Chung SS & Park YP Blood Advances;1(26):2572-8

5. MDS: Abnormal haematopoiesis
Myelodysplastic Syndrome
Anemia, infection, bleeding

6. Prognostic Scoring System for MDS

8. Steensma Blood Cancer Journal (2018) 8:47

9. Symptomatic MDS bleeding Infections fatigue, SOB +/- Iron chelation
Medications:
Tranexamic acid
Antibiotics
Antiviral agent
Anti-fungal agent
(TPO receptor agonists)
bleeding
Infections
fatigue, SOB
+/- Iron chelation

10. Anemia – Trial of Erythropoietin Replacement Therapy (ERT)
Response rate predicted from:
Serum EPO level
Transfusion requirements
74% chance of responding when EPO < 500 U/L, <2 units RBC/mth
7% if EPO > 500, >2 units RBC/mth
Target Hb g/L
Synergy with GCSF

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12. Other therapies for lower-risk mds
Lenalidomide
Immuno-modulating agent
MDS with del(5q) with anemia
10mg/d for 21d out of 28d
Response in 4-6 weeks
Rise in Hb of 32 g/L
% achieve transfusion independence, 30-40% cytogenetic remission
Improves survival (2y OS 90%v74%)
S/E: low neutrophils, low platelets, rash, GI, ? secondary malignancy
Immunosuppressive therapy (IST)
ATG + cyclosporine
More likely to work in patients:
60y/o or younger
Low-risk disease
BM blasts < 5%
Bone marrow hypoplasia
Normal cytogenetics
HLA-DR15
PNH clone

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14. The only cure for MDS is Hematopoietic Stem Cell Transplantation

15. Myelodysplastic Syndrome: a disease mostly of the elderly
Mean age at diagnosis 70-75y
Incidence : 4.9 per 100,000/year
<40y per 100,000/year
70-79y per 100,000/year
>80y per 100,000/year
Buckstein R. Leuk Res 2009;33:1313-8
Williamson PJ, et al. Br J Haematol. 1994;87:743

17. Co-morbidities affect transplant outcomes
Sorror et al, Blood; 106(5):

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19. Hypomethylating agents

20. Effect of Azacitidine in Higher-risk MDS (>/= IPSS-2)
Fenaux et al, Lancet Oncol 2009
358 patients
Median OS: vs 15 mths
Alive at 2 years: % vs. 26%
Transformation to AML: 11.5 vs. 17.8%

21. Agents iN clinical trial
Hypomethylating agents (HMAs)
Decitabine iv
Guadecitabine (SGI-110)
Oral azacitidine (CC486)
Oral decitabine (Cedurazine)
Erythroid Stimulating Agents
Luspatercept
Thrombopoiesis Stimulating Agents
TPO mimetics
Romiplostin (intectable)
Eltrombopag (oral)

22. Timing of Transplant in Lower-risk MDS
De Witte et al Blood;127(13):

23. Thank you
QUESTIONS?