Myelodysplasia. Dr John Barry

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1 Myelodysplasia Dr John Barry

2 Myelodysplasia Group of heterogenouus bone marrow disorders that are due to a defect in stem cells. Increasing bone marrow failure leading to quan>ta>ve and qualita>ve abnormali>es in all 3 myeloid cell lines

3 Myelodysplasia Most people die from consequences of marrow failure Transforma>on into acute myeloblas>c leukaemia occurs in up to 30% of cases.

4 Pathophysiology Chromosomal abnormali>es present in 40 70% Increasing frequency in more severe disease RAEB T 100% Del(5q), Monosomy 7 or del (7q) most common? Tumour suppressing gene

5 Classifica>on

6 WHO Classifica>on

7 Incidence 4.1 per 100,000 average incidence Increases with age Median age of 65 at presenta>on > 80 yrs : 89 per 100,000

8 Subtype Incidence R. A. 21% R. A. with ringed Sideroblasts 17% R. A. with excess blasts 37% R. A. with excess blasts in transforma>on 12% C.M.M.L. 13%

9 R.A. with ringed sideroblasts

10 Presenta>on Pallor in 60% Petechiae in 26% Cutaneous Manifeta>ons Sweet s Syndrome (acute febrile neutrophillic dermatosis) Granulocy>c Sarcoma

11 Sweet s Syndrome

12 Presenta>on Splenomegaly, hepatomegaly, and lymphadenopathy uncommon Excep>on being CMML, massive splenomegaly in 25% associated with hepatomegaly and lymphadenopathy Auto immune, vasculi>s, pleural effusions, monoar>cular arthri>s

13 Presenta>on Oben asymptoma>c Failure of one or more cell lines resul>ng in pancytopenia in 50% of cases Anaemia Less than 5% have isolated neutrophilia, thrombocytopenia, or monocytosis in absence of anaemia

14 Presenta>on Anaemia Low re>culocyte count Normochromic or Macrocy>c (RARS, hypochromasia) Erythyroid Hyperplasia EPO levels inversely related to anaemia but may be subop>mal in some subtypes

15 Presenta>on Leukopenia Absolute neutropenia in 50% Monocytosis (especially CMML) Thrombocytopenia in 25% at presenta>on Hypercellular bone marrow

16 Differen>al Dx Megaloblas>c Anaemia Aplas>c Anaemia Myelofibrosis Atypical CML HIV infec>on

17 Exclude Vit B12 and Folic acid deficiency Alcohol Medica>ons; Valproic acid Prior Radiotherapy and/or Chemotherapy Occupa>onal exposure to chemicals

18 Treatment Dependant of mul>ple factors Co morbidi>es Age Subtype of myelodysplasia Likelihood of adverse effects

19 Goals Control of symptoms Quality of life( decrease toxic S\E) Improving survival Decrease progression to AML

20 Interna>onal Prognos>c Scoring System

21 Prognosis

22 Treatment Dependant on Age IPSS Performance Status

23 Treatment Suppor>ve Poor performance status >60yrs, low intermediate 1 risk

24 Treatment Low intensity <60yrs, good or excellent performance status, low or intermediate 1 risk >60yrs, good performance status, intermediate or high IPSS risk

25 Treatment High Intensity <60yrs, good performance status, Intermediate or High IPSS risk

26 Treatment Suppor>ve Care An>bio>cs Red Cell Transfusions Platelets if ac>vely bleeding

27 Treatment G CSF EPO Best response in most karyotypically normal subtype Decreased posi>ve response over >me Ini>al delay in treatment response may be seen Interleukin 2

28 Treatments Cytarabine 20% remission rate 50% adverse effects Azaci>dine Pyrimidine analog of cy>dine 23% response rate 21 v 13 months median transforma>on to AML

29 Treatments Deci>bine Pyrimidine analog Response rate of 25%, 64% in Intermediate and high risk groups Increase median survival from 0.5 to 1.2 yrs in high risk pts Major S\E

30 Treatment High Intensity An>leukaemic Tx Cytarabine +\or Daunorubicin Mitoxantrone Etoposide

31 Haematopoie>c Cell Transplanta>on Limited by donor availability Age Limit < 60yrs Low risk pts: 60% cure rate Intermediate risk pts: 40% cure rate Up to 40% 5 year mortality

32 Specific Treatments HLA DR2 an> thrombocyte globulin or atg + cyclosporine 60% remission in low to intermediate risk groups 5q minus syndrome : lenalidomide in one study Low EPO and low transfusion requirement EPO and G CSF response in up to 50%,

33

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