CB-1 MDS Classification and Prognosis John M. Bennett, MD University of Rochester Medical Center Hematomorphologist Chair, MDS Foundation

CB-2 Primary Myelodysplastic Syndromes  Malignant disorders characterized by – Ineffective hematopoiesis (≥ 1 lineage) – Variable % of leukemic blasts  Median age is 70  30% progress to AML  US incidence: ~15,000 cases annually  US prevalence: 35,000 to 55,000  Majority present with moderate to severe anemia  Del 5q is associated with transfusion-dependent refractory anemia

CB-3 All 3 prognostic variables required to generate IPSS score International Prognostic Scoring System Greenberg P, et al. Blood. 1997;89: Score value Prognostic value Bone marrow blasts, %< – KaryotypeGoodIntermediatePoor–– Del 5qSole1 otherMultiple–– Cytopenias, n ––– IPSS total score ≥ 2.5 IPSS Risk categoryLowIntermediate-1Intermediate-2High

CB-4 IPSS Risk Category Correlates With MDS Survival Outcomes Time, yr Percent surviving Low Int-1 Int-2 High Greenberg P, et al. Blood. 1997;89: del(5)(q13q33)

CB-5 Management of Low/Int-1-Risk MDS Treatment:  Recombinant erythroid growth factors  5-azacytidine (Vidaza ® )  Transfusions Patients with MDS present with anemia and fatigue

CB-6 Transfusions: An Imperfect Solution  Transient Hct improvement  Hct not restored to normal  Associated morbidities – Iron overload (250 mg iron/unit) Unable to be phlebotimized Requires chelation – Infectious diseases – Transfusion reactions  Demand on blood supply  Impact on patients’ lives

CB-7 Impact of Lenalidomide on a Patient  Patient # – 84-yr-old female with Low-Risk MDS; del 5q – Required 116 RBC units over 54 mo EPO resistant Chelation therapy for iron overload – Started lenalidomide: Dec 03 (Hgb: 8.2 g %) – Last unit transfused: Feb 04; Hgb: 10.0 g % by Day 50 – Hgb 13.3 g % by Apr 04 – Has remained at that level to present – Tolerating phlebotomy for iron overload – Marrow morphology and cytogenetics normalized – Remains on study in complete remission