Anemia in the Elderly

Transcript

1. Anemia in the Elderly Robert W Warner MD Heartland Oncology and Hematology
2. House Calls Radio Show Sunday 9:30 am The Chuck & Don Show Tuesday 9:35 am KMA 960 AM kma960.com HeartlandOncology.com On the Radio
3. Red Blood Cells • Normal Hgb 12-16gm/cubic mm • Size 7 micrometers • Lifespan 110days
4. Red Blood Cells Egelberg [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons
5. • Blood loss • Hemolysis • Hypoproliferative Causes of Anemia
6. Reticulocytes • 2-3 days after rbc leaves marrow • >75,000 /cubic mm in anemic patient
7. By User:A. Rad, svg file drawn with FlashMX by birdy [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons
8. Hypoproliferative Anemia • Fe Deficiency • B12 Deficiency • Folate Deficiency • Thyroid Hormone Deficiency • Erythropoietin Deficiency • Bone Marrow Derangement
9. Myelodysplastic Syndrome (MDS) • Represents a heterogeneous hematopoietic disorder in which mature blood cells are derived from an abnormal multipotent progenitor cell. • Ineffective erythropoiesis. • Heterogenous spectrum of presentation • Morbidities from cytopenia to potential to evolve in to AML
10. • Incidence among general population is 5/100,000 • Above 70 years is 22-45/100,000 Myelodysplastic Syndrome (MDS)
11. • Clonal expansion of hematopoietic progenitor cells • Aging is a factor in the evolution of clonal myeloid disorder • 49% had abnormal karyotype • Chromosomal aberrations are either deletion or gain Pathogenesis of MDS
12. Pathogenesis of MDS • Genetic instability - 35% new clonal cytogenetic abnormality during the course of disease. • Specific mutation initiate or causing progression of the disease is not known • Therapy related MDS ◦ Alkylating agents- chromosome 5 and 7 ◦ Epiphyllotoxin – t(11q23)
13. Diagnosis • Bone marrow and peripheral blood morphology are keys to establishing a diagnosis of MDS. • Flow cytometry may provide complimentary information but cannot establish a diagnosis of MDS in the absence of marrow morphology. • Cytogenetics provides additional information on prognosis and treatment decisions
14. Myelodysplastic Syndrome (MDS) Prognostic Variable 0 0.5 1.0 1.5 2.0 BM blasts (%) <5 5-10 --- 11-20 21-30 Karyotype Good Int Poor Cytopenia 0/1 2/3 Score Value Scores Low: 0 Int-1: 0.5 - 1.0 Int-2: 1.5 - 2.0 High: 2.5 Cytogentics Good: Normal -Y del(5q) del(20q) Poor: Complex (>=3abr) Chromosome 7 anom. From Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes, Blood. 1997;89:2079-88
15. French-American-British & World Health Organization Classifications of Myelodysplastic Syndromes Shannon, K. et al. ASH-SAP 2007;2007:228-242 FAB WHO Dysplasia(s) RA 5q-syndrome RA RCMD MDS-U Erythropoietic Erythropoietic 2-3 Lineages 1 Lineage RARS RARS RCMD-RS Erythropoietic 2-3 Lineages RAEB RAEB-1 RAEB-2 1-3 Lineages 1-3 Lineages RAEB-t AML
16. Treatment of MDS • Observation • Supportive treatment with blood transfusion • Recombinant Epo, + /-GCSF • Chelation of iron in patients who are receiving blood transfusions • Hypomethylating agents like azacitidine, decitabine • Immunomodulator and antiangiogenics like lenolidamide • ATG and Cyclosporin • HSCT
17. Vidaza 5-azacitidine • Pyrimidine Nucleoside Analog of Cytidine • Hypomethylation of DNA • RX 5-7 days IV or SQ per month • Minimum 4 Cycles to Assess Response • Duration: Until Failure
18. Vidaza 5-azacitidine • CALGB study: 191 pts vs BSC • 23% response vs 0% • Median time to leukemic transformation 21 vs 13 mo • QOL significantly improved on vidaza arm
19. Case Study • A 65-year-old woman presents to her primary care physician with complaints of fatigue and decreased exercise tolerance of several months' duration. History is negative for recent viral infections including human immunodeficiency virus, prior treatment with chemotherapeutic agents, ethanol exposure, lead, and benzene. • She has no hx of chronic hepatitis, RA • Her physical examination is unremarkable with the exception of pale mucous membranes and sinus tachycardia. A complete blood cell count reveals the following:
20. Case Study • WBC 3000 • ANC 1600 • Platelet count 40,0000 • MCV 104 • Hgb 8.9
21. Case Study • Differential diagnosis • Iron deficiency anemia = Microcytic, abnormality in iron studies , bone marrow iron is the best diagnostic test • Vitamin B12/Folate deficiency is usually Macrocytic • Anemia of chronic disease is NC NC • Hemolytic Anemia : Coombs test • Myelodysplastic syndrome: BM morphology is diagnostic
22. Case Study • Full hematologic workup is inconclusive as to the exact cause of her anemia. • Vitamin B12, folate normal • Serum iron, ferritin, TIBC, retic count all normal • GFR is 67ml/mnt and Epo level is less than 100 unit • Normal LDH, haptoglobin and total bilirubin
23. Case Study • Rx vidaza 75mg/sqm x 5d IV q28d • No change blood counts or transfusion dependence x3mo • Counts after 5 courses Rx WBC 5,500; Hgb 11.4gm; Plt 165,000 • No further transfusions required
24. Dacogen 5-aza-2- deoxycytidine • Pyrimidine nucleoside analog of cytidine • Inhibits DNA methylation • Rx IV 5 days per month • Minimum 8 cycles to assess response • Duration until failure
25. Dacogen 5-aza-2- deoxycytidine • ADOPT trial 99pts • Overall response 32% • 50% of assessable responders had cytogenic response • 65% of pts were required hospitalization at some point, most often due to cytopenic complications
26. Case Study • 74 year white male • WBC 1,100 • Hgb 7.6gm • Plt 17,000
27. Case Study • Rx Dacogen 20mg/sqm IV X 5d q28d • RBC transfusion dependence resolved after 5 courses • Plt transfusion dependence resolved after 7 courses • Remission counts: WBC 8,500 (also receives g-csf); Hgb 11.2gm; Plt 85,000
28. WHO Classification of the 5q– Syndrome30 Blood Findings Bone Marrow Findings Macrocytic anemia Normal to increased megakaryocytes with hypolobulated nuclei <5% Blasts <5% Blasts Platelets normal or elevated No Auer rods Isolated 5q deletion
29. Revlimid Lenalidomide • Immunomodulatory and antiangiogenic • Rx 10mg po qd • Rx with steroids • Dose adjustment for cytopenias • Thalidomide analog
30. Lenalidomide has immunomodulatory and antiangiogenic drug for 5q- syndrome • Multicenter phase II trial of lenalidomide, for del(5q31) MDS patients with transfusion- dependent anemia • Cytogenetic responses were seen in 76% of the transfusion-independent patients • 55% of these patients achieving complete cytogenetic remission • 64% of 148 RBC transfusion-dependent patients with del(5q31) MDS achieved transfusion independence J Clin Oncol 23:2s, 2005 (suppl; abstr 5)
31. Lenalidomide has immunomodulatory and antiangiogenic drug for 5q- syndrome • Rate of transfusion independence was higher in patients with an isolated del(5q) than in del(5q) patients with additional chromosomal abnormalities 69% v/s 49% (P = .003). • The median response duration has not yet been reached, with a median follow-up of 9.3 months • Neutropenia and thrombocytopenia were the most common adverse events in this study, necessitating treatment interruption or dose reduction J Clin Oncol 23:2s, 2005 (suppl; abstr 5)
32. Lenalidomide has immunomodulatory and antiangiogenic drug for 5q- syndrome • These results indicate that lenalidomide is highly effective in achieving durable transfusion independence and cytogenetic remission in MDS patients with del(5q31) J Clin Oncol 23:2s, 2005 (suppl; abstr 5)
33. Robert W Warner MD Heartland Oncology and Hematology Anemia in the Elderly