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MDS Classification and Prognosis

John M. Bennett, MD

University of Rochester Medical CenterHematomorphologist

Chair, MDS Foundation

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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

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All 3 prognostic variables required to generate IPSS score

International Prognostic Scoring System

Greenberg P, et al. Blood. 1997;89:2079-2088.

Score value

Prognostic value 0 0.5 1.0 1.5 2.0

Bone marrow blasts, % < 5 5 - 10 – 11 - 20 21 - 30

Karyotype Good Intermediate Poor – –

Del 5q Sole 1 other Multiple – –

Cytopenias, n 0 - 1 2 - 3 – – –

IPSS total score 0 0.5 - 1.0 1.5 - 2.0 ≥ 2.5

IPSS Risk category Low Intermediate-1 Intermediate-2 High

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IPSS Risk Category Correlates With MDS Survival Outcomes

Time, yr

Per

cen

t su

rviv

ing

100

80

60

40

20

00 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Low

Int-1Int-2High

Greenberg P, et al. Blood. 1997;89:2079-2088.

del(5)(q13q33)

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Management of Low/Int-1-Risk MDS

Treatment:

Recombinant erythroid growth factors

5-azacytidine (Vidaza®)

Transfusions

Patients with MDS present with anemia and fatigue

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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

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Impact of Lenalidomide on a Patient

Patient #014-3002– 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