Presentation on theme: "MDS - Diagnosis and Treatments"— Presentation transcript:
1 MDS - Diagnosis and Treatments Dr Helen Enright, Adelaide and Meath HospitalDr Catherine Flynn, St James Hospital
2 Overview What is myelodysplasia? Symptoms Diagnosis and prognosis Myelodysplasia therapySupportive careNon-intensive therapyBone marrow transplant
3 Age-related Incidence of MDS (per 100,000)Age in 5-year blocksWilliamson PJ, et al. Br J Haematol Aug;87(4):743-5.
4 What causes MDS? Damage to marrow cells Previous chemotherapy Previous radiation therapyExposure to marrow-damaging agents (??)Predisposition?????
5 What is Myelodysplasia? Myelodysplastic syndromes are a group of blood stemcell disorders of varying severity typified by:Low blood counts (marrow failure)Typical marrow featuresPossibility of progressing to leukaemia (in some patients)
6 What is Myelodysplasia? Normal bone marrow makes healthy blood cells (red, white and platelet cells)In MDS, the bone marrow makes the blood cells badly (dysplasia), causing low blood counts and cells that don’t work very well
7 Myelodysplasia Symptoms None – abnormal blood countFatigue and shortness of breath- caused by anaemia (low red cells)Bruising and bleeding- caused by low platelet cell countInfection- due to low numbers and/or poorly functioning white cells
8 Diagnosis Specialist tests for myelodysplasia Morphology Flow cytometryCytogeneticsBone marrowsample
10 Diagnosis WHO Classification of myelodysplasia Entity Bone marrow blastsCytogenetics5q- syndrome<5%5q- onlyRefractory anaemiavariousRefractory cytopenia multilineage dysplasia (RCMD)Refractory anaemia excess blasts-1 (RAEB-1)5-9%RAEB-210-19%Chronic myelomonocytic leukaemia -1 (CMML-1)<10%CMML-2
11 International Prognostic Scoring System LowLOWHIGHINT-2INT-1SEVERITY
12 Therapeutic Options Low Risk MDS – Main problem is anaemia, sometimes thrombocytopeniaHigh Risk MDS –Main problem is bone marrow failure and risk of leukaemia
13 Treatment : general concepts Treatment choices should take into account:What type of MDS doesthe patient have?How aggressive is their MDS?Are any symptoms particularly bothersome?How does the patient want to be treated?Is curative therapy appropriate?What age?What other problems?
14 Treatment Supportive care What is supportive care?Supportive care is any medicine or device that helps to make symptoms go away, or makes it easier and safer for the patient to receive ‘active’ treatment…..
15 Supportive care Red cell transfusion Anaemia causing symptoms Platelet transfusionLow platelets-bleeding & bruisingPlanned surgical operationErythropoietinAnaemiaGranulocyte-colony stimulating factorInfections associated with low white countAntibioticInfectionsIron chelation therapyPatients with low-risk disease with high transfusion requirement
16 Treatment of Anaemia in MDS TransfusionGrowth FactorsSymptomatic anaemia in low risk MDSImmunosuppression withAntithymocyte globulinLenalidomide in 5q-16
17 Myelodysplasia supportive care Red cell transfusionMany patients will develop symptoms due to anaemiaRed cell transfusion is the commonest way anaemia is treatedThe number and frequency may vary, but generally needs increase over time
18 Myelodysplasia supportive care Platelet transfusionPlatelet transfusion should be reserved for patients with bruising or bleeding symptomsPlanned surgery, dental extraction may also need to be covered by platelet transfusion
19 Myelodysplasia supportive care ErythropoietinMay improve anaemia in patients with MDSMay reduce red cell transfusion needEPOSeems to work best when given withwhite cell growth factor G-CSFHas to be given by injection
20 20 Years experience of erythropoietin +/- G-CSF therapy in MDS Overall response rate ~20-40%Best response group ~ 60-70%(Low erythropoietin blood levels, not needing much transfusion)
21 Questions regarding Erythropoietin in MDS Is there a quality of life benefit for EPO responders?Is EPO therapy cost-effective?Is there a survival advantage for EPO responders?
22 Myelodysplasia supportive care Iron overloadIron chelation (removal)Long term red cell transfusion can lead to increased iron that the body can’t get rid ofIncreased iron may damage organs like the heart, liver and pancreasConsidered in transfusion dependent MDS patients with low risk MDS with a high transfusion requirementDesferrioxamine (injection) and Deferiprone (tablet) are used to remove iron
23 Which patients if any should get iron chelation? IPSS score low or int-1Ferritin should be ng/ml or clinical or radiological evidence of iron loadingThis would often correlate with units of red cells transfusedSome candidates for transplant in whom there is a significant delay until the procedure
24 We have still not answered two major questions in low risk MDS! Is erythropoietin therapy more beneficial than transfusion?Is iron chelation therapy beneficial?:
25 Cinical Trials may answer some of these questions Erythropoietin versus PlaceboIron chelation versus Placebo
26 Best supportive careRed cell transfusion as required – to maintain quality of lifeAntibiotics for treatment and prevention of infectionsG-CSF during infection (if white cell count low)Iron chelation therapy if needed
27 MDS Treatment Options Can we move beyond supportive care to Change the course of MDS?Delay progression?Delay/prevent leukaemia developmentCure????
29 Myelodysplasia Non-intensive therapy 5q- Syndrome MDS5% of MDS patients have 5q-MDSUsually female‘Good’ platelet countAnaemiaChromsome 5q missingGood prognosisLenalidomide Should be considered for 5q- syndromeOral medicationEliminates need for transfusion in 67% of patients
31 Transfusion Independence Response Lenalidomide in 5q- syndrome 4.6 ( )99 (67%)Average time to response, weeks (range)Transfusion IndependenceN = 148See BD for data31
32 Azacitidine in high-risk MDS It has been suggested that azacitidine may switch on important anti-cancer genesSignificant benefit to patients with aggressive MDS when treated with Azacitidine in clinical trials (USA and Europe)Benefits include:Reduced red cell transfusionImprovement in survivalLess chance of MDS deterioratingResults not influenced by patient age, blast cells, karyotype
33 AzacitidineDrug administered by injection (oral preparation in development)Well toleratedMay be appropriate for high risk MDS patients who are not candidates for transplantation
34 Intensive Chemotherapy for MDS Sometimes used in high-risk MDSCan reduce leukemia cells in patients who are progressingSometimes used in patients prior to transplantInvolves long hospitalizationNot a cureMarrow Transplant may be considered for some patients
35 SummaryMDS is not one disease, but a group of disorders that cause the bone marrow to fail2. Diagnosis may require a number of special tests on bone marrow and blood, and may need repeating before a firm diagnosis can be made!3. Treatments range from ‘supportive’ to the ‘intensive’. Modern treatments, including BMT are, increasingly relevant to many patients with MDS
36 MDS in Ireland Need for patient support group Resources needed for Irish MDS patientsNational MDS RegistryInformation regarding incidence in IrelandDiagnosis in older patientsIron-overload problemsIssues related to diagnosis and managementData on >300 patients