1. HS 4160 Critical Scientific Analysis
Week 3: Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies
HS 4160 Critical Scientific Analysis

2. Objectives
Learn how to quickly locate background information for a given topic.
Outline structure of a systematic review and meta-analysis paper.
Determine elements of an Introduction section.
Define elements of a Discussion section
Critically extract information from tables.
Discuss strength and weakness of a meta-analysis paper.

4. Hematopoiesis Pools Stem cell and bone marrow pool overlap.
Not all cells in the peripheral blood are actively functioning. So you have granulocytes and thrombocytes can be resting or in storage.

5. Cytokines and Interleukins
GM-CSF
Stimulates proliferation of granulocyte and macrophages/monocytes
G-CSF
Stimulates proliferation of neutrophil and enhances function
M-CSF
Stimulates proliferation of monocytes/ macrophages
Interleukin
Stimulates proliferation and differentiation of specific cell lines and work together with CSFs
Erythropoietin
Erythropoietic stimulating factor produced in the kidney
Thrombopoietin
Hormonal factor that controls production and release of platelets

6. MDS Myelodysplastic Syndromes
Myeloid Disease
MDS Myelodysplastic Syndromes

7. MDS Failure of differentiation Hypercellular marrows.
Peripheral cytopenias.
Displastic blood cells.
Preleukemia – 1/3 to AML.

8. MDS is caused by Poor hematopoietic maturation
Poor hematopoietic differentiation
Over production of G-CSF
None of the above

9. Clinical Overlap/Associations

10. MDS is a form of blood cancer
True
False

11. FAB vs. WHO FAB Classification WHO classification RA RARS RAEB RAEB-T
CMML
WHO classification
Myelodysplastic Syndromes RA
RARS
RCMD & RCMD-RS
RAEB-1 & RAEB-2
MDS Unclassified
MDS del(5q)
Myelodysplastic/Myeloproliferative Diseases
CMML
Atypical CML
Juvenile CMML
MDS/MPD, unclassified

12. WHO Classification MDS RA Refr. cytopenia w. multlineage dysplasia
with ringed sideroblasts
without ringed sideroblasts
Refr. cytopenia w. multlineage dysplasia
Refr. Anemia with excess blasts
5q- syndrome
MDS, unclassifiable

13. Lab Tests

14. Which of the following is a main clinical feature of MDS?
>30% blast cells in BM
Respond well to epo
Refractory anemia
Reduced risk to AML

15. Ringed Sideroblast

16. Vitamin A Magnesium Iron Folic acid
Blue granules seen in ringed sideroblast indicate the cell could not use___
Vitamin A
Magnesium
Iron
Folic acid

17. Chromosome Changes in MDS

18. Chromosome Changes in MDS

19. Chromosome abnormality most frequently seen in MDS
del(3)
del(5)
add(10)
None of the above

21. 5q Deletion Syndrome Deletion span 5q13-5q33. Most frequent in 5q31.
Genes related to hematopoiesis.

22. Cytogenetic Predictors
In one study, patients with 5q- had the best cumulative median survival (115 months).
Patients with 20q- and –Y had a favorable course.
Abnormalities of chromosome 7, 8 and complex aberrations had a poor outcome (less than 10 months).
AML evolution was most frequent in patients with complex abnormalities (50%)and with trisomy 8 (33%).

23. Genetics 5q- syndrome (women, megakaryocyte anomalies)
del 17p (pseudo Pelger-Huet anomaly, therapy related)
Complex cytogenetic (chromosomes 5 & 7) unfavorable prognosis
Del(20q) (erythroid and megakaryocytes)
Abnormal Ch 3 (abnormal megas)

24. Molecular Abnormalities in MDS
Gene
Type of anomaly
Incidence (%)
RAS
(N or K)
Point mutation
(codon 12, 13 or 61)
10-30%
P53
Point mutation or deletion of other allele 5
FMS
(encodes M-CSF receptor)
(codon 969 or rarely 301)
5-10

26. Chromosome abnormality seen in MDS with most favorable outcome?
inv(3)
del(5q) +8
t(1;3)

27. IPSS Definition
International Prognostic Scoring System

28. IPSS Scoring System & Risk:

29. Overall IPSS score and survival
Overall score: Median survival:
Low
years
Intermediate
1 (0.5 or 1) years
2 (1.5 or 2) years
High
> years

30. Lower IPSS score means
Good survival
Medium survival
Poor survival
None of the above