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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