Presentations today

• Epidemiology

• Pathobiology (Ebert, Scadden)

• Diagnosis (van de Loosdrecht)

• Prognosis (Greenberg)

• Therapies (Fenaux)

MDS therapy

Therapy 5-azacytidine Decitabine Lenalidomide BMT

Impact on survival Positive

? ? ?

Genetic lesions in patients with myelodysplastic syndromes.

Bejar R et al. JCO 2011;29:504-515

MDS as a ribosomopathy??

Narla et al., Blood(2010)

MDS as a disorder of splicing??

MDS as a disorder of splicing??

MDS as a epigenetic disorder??

MDS as a disorder of epigenetics??

Prognostic scoring system for therapeutic decision making in MDS patients

Professor of Medicine; Stanford University Cancer Center; Stanford, CA

Peter Greenberg, MD

Novel agents and combinations for the treatment of MDS

Professor of Hematology; Hopital St. Louis; Paris, France

Pierre Fenaux, MD

Improving the role of flow cytometry for the characterization of MDS

Professor of Hematology; VU University Medical Center; Amsterdam, The Netherlands

Arjan van de Loosdrecht, MD, PhD

Marrow microenvironmental abnormalities in MDS

Gerald and Darlene Jordan Professor of Medicine; Harvard University; Cambridge, MA

David Scadden, MD

Molecular abnormalities and their impact on prognosis of MDS

Associate Professor of Medicine; BWH; Harvard Medical School; Cambridge, MA

Benjamin Ebert, MD, PhD

YARDVILLE, NJ

Where are we?

Overview:

The Taub Foundation Grants Program for Myelodysplastic Syndromes (MDS) Research was created to support high-impact, innovative translational research to understand the underlying causes of MDS and to advance its treatment and prevention. The Program specifically focuses on MDS research, exclusive of AML and MPN.

The Taub Foundation Grants Program

for MDS Research is administered by

The Medical Foundation division.

Eligibility:

• All applicants must hold a faculty appointment at a non-profit, non-governmental academic, medical, or research institution in the United States.

• United States citizenship is not required; visa documentation is not required.

• Only one application may be submitted per applicant.

Join the RFA

Mailing List: Please contact EJohnstone@hria.org or call 617-279-2240 ext. 710

The Taub Foundation

Grants Program

for MDS Research

A PROGRAM OF THE HENRY AND

MARILYN TAUB FOUNDATION

PROGRAM LAUNCH: Wednesday, January 8, 2014

PROPOSAL DEADLINE: Tuesday, March 25, 2014

12:00 Noon, U.S. Eastern Time

FUNDING PERIOD and

AWARD AMOUNT:

November 1, 2014 – October 31, 2017

Three-year awards at $200,000

per year

CME Pre-Test

1. The hematopoietic microenvironment has NOT been shown to have which of the following features: a. Induction of myelodysplasia in humans

b. Induction of myelodysplasia in mice

c. Chromosomal abnormalities in patients with MDS and AML that associate with clinical outcomes

2. Mesenchymal cells of the hematopoietic microenvironment: a. are generally static and long-lived

b. Are highly plastic and may undergo conversion to hematopoietic cells

c. Are dependent on a stem cell model for cell replenishment

Correct answers: 1. a 2. c

3. Indicate the one feature which is not a critical variable related to the clinical outcome of an MDS patient:

a. Marrow blasts

b. Cytogenetics

c. Depth of blood count levels

d. Age

e. Gender

4. Which of the following variables are also important to an MDS patient’s overall survival?

a. Serum epo levels

b. Specific gene mutations

c. Lymphocytosis

d. Number of gene mutations

e. b and d

f. a and c Correct answers: 3. e 4. e

5. Should Flow Cytometric analysis of dysplasia in MDS be part of a diagnostic approach in 2013? a. No, since there are no validated flow cytometric protocols available

with lack of perspective clinical evaluation.

e. Yes, in any patient with cytopenia with suspected underlying MDS.

f. Yes, in patients with suspected MDS in the flow cytometric analysis is performed according to international guidelines.

6. Should the Results of a Flow Cytometric analysis in MDS be part of an integrated diagnostic report? a. No, since the flow cytometric analysis has shown independent

diagnostic and prognostic value in MDS.

b. No, since there is no relation of flow cytometric results with morphology, cytogenetic and molecular analysis.

c. Yes, flow cytometric results add significantly in cases in which morphology and/or cytogenetics are not conclusive.

Correct answers: 5. c 6. c

7. Mutations in which of the following genes are

associated with a complex karyotype and poor

prognosis in MDS?

a. TET2

b. TP53

c. SF3B1

8. Multiple genes in which of the following pathways or

cellular processes are recurrently mutated in MDS?

a. RNA splicing

b. Cohesins

c. DNA methylation

d. All of the above

Correct answers: 7. b 8. d

9. All the following statements concerning first line treatment of MDS are true, except one:

a. Erythropoietic stimulating agents (ESA) are generally the first line treatment of anemia in lower risk MDS without del 5q.

b. Lenalidomide is generally the first line treatment of anemia in lower risk MDS with del 5q.

c. Several drugs, when combined with hypomethylating agents (HMA), can improve survival compared to a HMA alone.

d. About 15% of MDS patients are candidates for allogeneic stem cell transplantation.

10. All the following statements concerning second line treatments of MDS are true, except one:

a. Outcome of higher risk MDS after failure/relapse from HMA treatment has recently been significantly improved by several new drugs.

b. TP 53 mutation is frequent in lower risk MDS with del 5q, especially in patients with lenalidomide failure.

c. The following drugs have shown some efficacy as second line treatment of lower risk MDS: HMA, Lenalidomide, antilymphocyte globulin.

d. Most patients with lower risk MDS end up receiving regular RBC transfusions.

Correct answers: 9. c 10. a