Myelodysplastic Syndromes, Red Cell Transfusion

1,655 views
1,558 views

Published on

Myelodysplastic Syndromes, Red Cell Transfusion Presentation by Pr. David Bowen, St James’s Institute of Oncology, Leeds Teaching Hospitals, UK

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,655
On SlideShare
0
From Embeds
0
Number of Embeds
17
Actions
Shares
0
Downloads
40
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Myelodysplastic Syndromes, Red Cell Transfusion

  1. 1. Myelodysplastic SyndromesMyelodysplastic Syndromes red cell transfusionred cell transfusion Pr. David BowenPr. David Bowen St James’s Institute of OncologySt James’s Institute of Oncology Leeds Teaching HospitalsLeeds Teaching Hospitals UKUK
  2. 2. MDS - age at diagnosisMDS - age at diagnosis RegistryRegistry Median age at diagnosis (years)Median age at diagnosis (years) DusseldorfDusseldorf 69-7369-73 PaviaPavia 65-7165-71 MD AndersonMD Anderson 6666 SW ThamesSW Thames 77 (77-78)77 (77-78) SEERSEER Mid-late 70sMid-late 70s ≥≥80y – 38%80y – 38% ≥≥70y – 33%70y – 33% HMRN YorkshireHMRN Yorkshire 7575 ELN MDS RegistryELN MDS Registry 74 (72.5-75)74 (72.5-75)
  3. 3. European LeukemiaNet (ELN)European LeukemiaNet (ELN) low-risk MDS registrylow-risk MDS registry ProspectiveProspective registry for newly diagnosed IPSSregistry for newly diagnosed IPSS Low/INT-1Low/INT-1 Recruiting from 11 countries, 107 sitesRecruiting from 11 countries, 107 sites Data collection at baseline and 6-monthlyData collection at baseline and 6-monthly – Haematological, MDS therapy (incl. transfusions),Haematological, MDS therapy (incl. transfusions), concomitant medication, co-morbidity, QoL (EQ-5D),concomitant medication, co-morbidity, QoL (EQ-5D), serum and urine samples.serum and urine samples.
  4. 4. ELN registry: Sorror Score of Co-morbidityELN registry: Sorror Score of Co-morbidity AU CZ FR GE GR ND RO SP SW UK 0.511.522.533.54 MeanSorrorScore Mean Score 2.4, range (0 to 11)
  5. 5. ELN registry patients at diagnosis:ELN registry patients at diagnosis: Past Medical History & TreatmentPast Medical History & Treatment Cardiac DiseaseCardiac Disease 28%28% Pulmonary DiseasePulmonary Disease 13%13% Diabetes MellitusDiabetes Mellitus 16%16% Thyroid DiseaseThyroid Disease 12%12% Anti –Hypertensive DrugsAnti –Hypertensive Drugs 37%37% Anti-PlateletAnti-Platelet 16%16% Cholesterol LoweringCholesterol Lowering 14%14%
  6. 6. French MDS Group practice surveyFrench MDS Group practice survey one week cross sectional study (n= 907 patients)one week cross sectional study (n= 907 patients) Median age = 74 yearsMedian age = 74 years Throughout the one week observationalThroughout the one week observational period:period: – ~5% patient episodes were in-patient~5% patient episodes were in-patient admission for transfusionadmission for transfusion – 31% all episodes were for red cell transfusion31% all episodes were for red cell transfusion – 61% patients required red cell transfusion61% patients required red cell transfusion Kelaidi et al, Haematologica 2010, 95, 892
  7. 7. French MDS Group practice surveyFrench MDS Group practice survey one week cross sectional study (n= 907 patients)one week cross sectional study (n= 907 patients) Kelaidi et al, Haematologica 2010, 95, 892
  8. 8. Transfusion frequencyTransfusion frequency Frequency of transfusion in weeks (n=185) mean = 2.7 median = 2.0 10.00 8.00 6.00 5.00 4.00 3.00 2.00 1.00 Service evaluation of chronically transfused patients at Leeds General Infirmary, 2006-2007
  9. 9. Transfusion totals by year - complete years 1+2 2 3 6 7 8 10 13 0 10 20 30 40 50 60 Yr 1 Yr 2 Patient Redcellunits/year Transfusion burdenTransfusion burden
  10. 10. Red cell transfusion as aRed cell transfusion as a negative prognostic factornegative prognostic factor:: WHO- based prognostic scoring systemWHO- based prognostic scoring system Cazzola & Malcovati Hematol/Oncol Clin North Am 2010, 24, 459
  11. 11. Complications of red cellComplications of red cell transfusion in MDStransfusion in MDS Fluit et al, Transfusion 1990, 30, 532
  12. 12. QuestionsQuestions Optimal transfusion strategy to maximiseOptimal transfusion strategy to maximise quality of life?quality of life? Optimal trigger for transfusion forOptimal trigger for transfusion for individual patients?individual patients? If, who, when to offer iron chelation?If, who, when to offer iron chelation?
  13. 13. Quality of life in transfused MDSQuality of life in transfused MDS patientspatients
  14. 14. ELN Registry: QoL - EQ-5D Health ScoreELN Registry: QoL - EQ-5D Health Score baselinebaseline AU CZ FR GE GR ND RO SP SW UK 0102030405060708090100 MeanHealthState Median Score 70 , range (4 to 100)
  15. 15. Health related quality of life by transfusion dependence /Health related quality of life by transfusion dependence / independence (EQ-5D)independence (EQ-5D)
  16. 16. Iron chelation – if, who, when?Iron chelation – if, who, when?
  17. 17. Ferritin concentration influencesFerritin concentration influences overall survivaloverall survival A. WHO RA, RARS, 5q- B. WHO RCMD/RS
  18. 18. Transfusion burden influences survivalTransfusion burden influences survival Malcovati, Haematologica 2006
  19. 19. Elevated serum ferritin as adverseElevated serum ferritin as adverse factor for transplant outcomefactor for transplant outcome Armand, P. et al. Blood 2007;109:4586-4588
  20. 20. French MDS groupFrench MDS group transfusion / chelation surveytransfusion / chelation survey 18 GFM centres surveyed for transfusion data in 200518 GFM centres surveyed for transfusion data in 2005 – Patients surveyed again in 2007Patients surveyed again in 2007 53/97 patients with IPSS Low/INT-1 received iron chelation therapy (ICT)53/97 patients with IPSS Low/INT-1 received iron chelation therapy (ICT) for at least 6 months (median duration = 36 mo, and median interval fromfor at least 6 months (median duration = 36 mo, and median interval from diagnosis to chelation = 23 mo)diagnosis to chelation = 23 mo) Overall survival from diagnosisOverall survival from diagnosis – 124 months for chelated patients124 months for chelated patients – 53 months non-chelated53 months non-chelated No information re. triggers or barriers for iron chelation (co-morbidity)No information re. triggers or barriers for iron chelation (co-morbidity) Arms areArms are balancedbalanced forfor – median ferritin concentrationmedian ferritin concentration – causes of deathcauses of death Arms areArms are imbalancedimbalanced for age, IPSS.for age, IPSS. Rose et al, Leuk Res 2010 Feb 1 online BUT
  21. 21. Prevalence of comorbid conditions among transfused and nontransfused patients with myelodysplastic syndromes (MDS) Goldberg S L et al. JCO 2010;28:2847-2852
  22. 22. Morbidity and mortality associatedMorbidity and mortality associated with iron overload in MDS patients?with iron overload in MDS patients? Cardiac failureCardiac failure – Malcovati et al, 2005Malcovati et al, 2005 Cause of death in up to 50% low-risk patientsCause of death in up to 50% low-risk patients Cardiac failure more common cause of deathCardiac failure more common cause of death in transfused patientsin transfused patients – Oliva et al, 2005Oliva et al, 2005 Cardiac remodelling (left ventricularCardiac remodelling (left ventricular hypertrophy)hypertrophy) – more frequent in transfusion-dependent patientsmore frequent in transfusion-dependent patients – Correlated with haemoglobin concentrationCorrelated with haemoglobin concentration
  23. 23. Cardiac pathologyCardiac pathology Cardiac failure is associated with anaemia in MDS?Cardiac failure is associated with anaemia in MDS? – High cardiac output stateHigh cardiac output state particularly at haemoglobin concentration < 8g/dlparticularly at haemoglobin concentration < 8g/dl – Stiff vascular bedStiff vascular bed – ?right heart strain ??pulmonary hypertension?right heart strain ??pulmonary hypertension – Renal impairment (cardio-renal-anemia syndrome)Renal impairment (cardio-renal-anemia syndrome) Transfusion practice across Europe varies but manyTransfusion practice across Europe varies but many countries transfusecountries transfuse only when Hb.<9 g/dl (oronly when Hb.<9 g/dl (or lower triggers)lower triggers)
  24. 24. 20 EPIC trial (β-thal major) •12 months Deferasirox •T2* increase from 11.2 ms to 12.9 ms •No change in LVEF Pennell et al, Eur H J, 2001, 22, 2171 Mamtani & Kulkarni BJH 2008, 141, 882 •Systematic review and meta-analysis •Iron chelators reduce myocardial iron content •No influence on LVEF Iron chelation therapy and T2* values in thal majorIron chelation therapy and T2* values in thal major
  25. 25. MRI T2* studies in MDS suggestMRI T2* studies in MDS suggest infrequentinfrequent cardiac iron loading:cardiac iron loading: Ferte et al, ASH 2006Ferte et al, ASH 2006 – 21 MDS patients21 MDS patients – 3/8 patients with > 100 units3/8 patients with > 100 units transfused had reduced T2* (transfused had reduced T2* (but 5/8but 5/8 did not!!did not!!)) – 2/3 had clinical cardiac failure2/3 had clinical cardiac failure – No correlation between T2* andNo correlation between T2* and serum ferritinserum ferritin
  26. 26. Deferasirox reduces serum ferritinDeferasirox reduces serum ferritin in MDSin MDS EPIC studyEPIC study 341 low/INT-1 MDS pts341 low/INT-1 MDS pts 12 months DFX: median 19 mg/kg/d12 months DFX: median 19 mg/kg/d Serum ferritin reduced by median ofSerum ferritin reduced by median of 253 mcg/l (for patients completing 12253 mcg/l (for patients completing 12 months)months) 49% withdrawal (13% drug related)49% withdrawal (13% drug related) Gattermann et al, Leuk Res 2010 34, 1143Gattermann et al, Leuk Res 2010 34, 1143
  27. 27. Deferasirox reduces serum ferritin andDeferasirox reduces serum ferritin and labile plasma iron in MDS:labile plasma iron in MDS: US03 studyUS03 study Year 1Year 1 Year 2Year 2 Number ofNumber of patientspatients 176176 8383 MedianMedian deferasirox dosedeferasirox dose 20 mg/kg/day20 mg/kg/day 20 mg/kg/day20 mg/kg/day Serum ferritinSerum ferritin reductionreduction 3397 to 25013397 to 2501 mcg/l (all)mcg/l (all) 3002 to 20693002 to 2069 mcg/l inmcg/l in 22 yearsyears (n=50 pts)(n=50 pts) Withdrawal rateWithdrawal rate 45%45% (10% drug related)(10% drug related) 42%42% (~15% drug related)(~15% drug related) List et al, ASH 2008 & 2009
  28. 28. Argument for chelation:Argument for chelation: Iron mediated organ toxicity is caused byIron mediated organ toxicity is caused by toxic free irontoxic free iron – NoNo direct evidence in MDS patientsdirect evidence in MDS patients – YesYes, there is evidence for oxidative stress in, there is evidence for oxidative stress in MDS cells but ?bystander or driverMDS cells but ?bystander or driver
  29. 29. We need toWe need to ironiron out someout some misconceptionsmisconceptions
  30. 30. Influence of iron chelation therapyInfluence of iron chelation therapy in MDS patientsin MDS patients OnlyOnly biochemical improvementsbiochemical improvements convincingly demonstrated to dateconvincingly demonstrated to date NoNo clinicalclinical benefit yet proven in MDSbenefit yet proven in MDS patients (survival, AML transformation)patients (survival, AML transformation)
  31. 31. Practical approachPractical approach My practice now:My practice now: – chelate younger / fitter patients with RARS,chelate younger / fitter patients with RARS, 5q-, RA5q-, RA Use Desferrioxamine (Deferiprone) andUse Desferrioxamine (Deferiprone) and rarely Deferasiroxrarely Deferasirox
  32. 32. Trial opportunityTrial opportunity TELESTO 2302 studyTELESTO 2302 study – Randomise deferasirox: placeboRandomise deferasirox: placebo (2:1)(2:1) – 3-5 year treatment period3-5 year treatment period – Several UK centresSeveral UK centres – Open in UKOpen in UK
  33. 33. Thank you for your attentionThank you for your attention Questions?Questions?

×