Organ dysfunction after HSCT Heart

Transcription

1 Organ dysfunction after HSCT Heart Annual Meeting of the EBMT, Paris 2011 EBMT Slide template Barcelona 7 February 2008 Educational 6 Tuesday, 5th April 2011 André Tichelli Chairman Late Effects Working Party

2 The Heart as a problem in HSCT Cardiac and cardiovascular dysfunction Frequent in a general population Spare data in patients after HSCT Many reasons that the heart can be affected in HSCT Heart complications may occur at any time during the HSCT Various parts of the heart can be the target Myocardial complications Arrhythmias Coronary artery diseases Endocardial and pericardial complications

3 Time sequence of cardiac and cardiovascular consequences after HSCT Pretransplant Peritransplant Early complications Late complications Disease related Mobilization Cardiac GVHD Cardiac Systemic sclerosis Amyloidosis Thalassemia Co morbidity Age Treatment related Radiation Chemotherapy Conditioning Stem cell infusion Endothelial damage syndrome Indirect cardiac consequences Infections Endocarditis Myocarditis Multiorgan failure Cardiovascular Cardiovascular risk factors

4 Pretransplant Factor Amyloidosis with cardiac involvement Outcome and TRM dependent on cardiac involvement Death during inductionmobilization Survival of 135 patients with AL amyloidosis according to the concentration of NT-proBNP and ctnt Accurate assessment of baseline cardiac dysfunction Cardiac biomarkers for the choice of treatment option NT-proBNP Cardiac troponins (ctnt) Clinical & echocariographic stratification inadequate Palladini G. et al. Blood 2010;116: 3426 Palladini et Merlini. Current Opin Oncol. 2011; 23:214.

5 Peritransplant factors Mobilization and stem cell infusion Mobilization Data usually not registered Problem in patients with pretransplant cardiac comorbidity Systemic sclerosis Initially death during mobilization 1.5% Actually G-CSF used alone No newly reported death Stem cell infusion DMSO related problems Cardiovascular in 40% Bradyarrythmias, blood pressure Other causes? erythrocytes and/or myeloid cells Volume overload Windrum P. et al. BMT. 2005; 36;

6 Early Complications Acute GVHD of the Heart Rare reports on acute GVHD involving the heart Prevalence could be underestimated Clinical manifestations reported Pericarditis Pericardial effusion with cardiac tamponade Myocarditis and heart failure Coronary artery disease Bradyarrythmia Large pericardial effusion Seven of 858 (0.8%) patients All unrelated HSCTs At median 229 days (42-525) after HSCT Non with other GVHD manifestation Successfully treated with intensification of immunosuppression Rhodes M. et al. BMT 2005; 36; Norkin M et al. BMT Rackley et al. BBMT :773.

7 Myocardial infiltration by donor type CD8+ T lymphocytes Roberts S. et al. Pediatr Blood Cancer 2006; 47;

8 Late Complications Late Cardiac Toxicity in Cancer Survivors Study on 1474 survivors of Hodgkin lymphoma Myocardial infarction Younger than 41 years at diagnosis Median follow-up 19 years Standardized mortality ratio myocardial infarction 3.6 congestive heart failure 4.9 Risk factors Mediastinal radiotherapy for coronary disease Anthracycline for congestive heart disease Aleman, B. M. P. et al. Blood 2007;109:

9 Late cardiac deaths after allogeneic and autologous HSCT Median age at HSCT Median follow-up Autologous HSCT n= (0.6-69) 7.6 ( ) Allogeneic HSCT n= (0.2-71) 9.5 (2-28.4) Total deaths Autologous HSCT Allogeneic HSCT Bhatia S. et al. Blood 2005; 105: Bhatia S. et al. Blood. 2007;110:

10 Cardiac function in children 5 years after allogeneic HSCT Prospective study on late cardiac effects 119 children treated with allogeneic HSCT Cardiac shortening fraction Results Increasing cumulative incidence Reduced cardiac dysfunction TBI+ anthracyclines 26% No TBI, no anthracyclines: 2% At 5th year 13% of the children presented asymptomatic cardiac abnormalities Uderzo C. et al. BMT. 2007; 39:

11 Late congestive heart failure after HSCT Cases with late congestive heart failure (CHF) after HSCT Cohort of patients 1 year post HSCT Autologous/allogeneic 60 cases with CHF 166 matched controls without CHF All case had clinical evidence of heart failure (stage C or D) Asymptomatic Patients with diminished cardiac function were not included Clinical presentation Dyspnea with exertion (96%) Dyspnea at rest (39%) Orthopnea (56%) Weight gain (48%) Fatigue (91%) Physical lung findings (65%) Extremity edema (78%) Armenian S H et al. JCO 2008;26:

12 Multivariate analysis of risk factors associated with late CHF Risk factor Odds Ratio 95% CI P-value Anthracycline, mg/m 2 < Pre-HCT cycles of chemo <0.01 Post-transplant comorbidity No comorbidity 1 comorbidity 2 comorbidities The variable that lead to early cardiac heart failure are different from those associated with late CHF Pretransplant factors are primarily responsible for the risk of associated late cardiac heart failure after HSCT

13 Late Cardiovascular Events after HSCT RR: 2.2; 95%CI: ; P=0.009) Tichelli A. et al. Blood. 2007; 110:

14 Cardiovascular risk factors are increased after allogeneic HSCT CV event Parameter with without P-value (n=20) (n=528) Hypertension 14 (70%) 59 (13%) <0.001 Diabetes mellitus 5 (25%) 26 (6%) Dyslipidemia 11 (58%) 65 (15%) <0.001 BMI 25 mg/m2 10 (56%) 128 (33%) Smoking 7 (41%) 49 (12%) Physical inactivity 12 (75%) 142 (44%) Tichelli A. et al. Haematologica. 2008; 93:

15 Predictive factors for late cardiovascular diseases after HSCT Pre-transplant factors - Radiation exposure Chest irradiation: Odds Ratio 9.5; P=0.03 Post-transplant factors - Presence of multiple cardiovascular risk factors 2 or more risk factors: obesity, dyslipidemia, hypertension, diabetes. Odds Ratio 5.2; P<0.01 Presence of pre-hsct cardiovascular risk factors was not associated with coronary artery disease Armenian SH et al. BBMT. 2010; 16:1138

16 Why cardiovascular risk factors are increased after allogeneic HSCT? Endocrine dysfunction Hypogonadism Growth hormone deficiency Hypothyroidism Insulin resistance Hyperleptinemia Total body irradiation No relation with Immunosuppressive treatment Chronic GVHD Taskinen M et al. J Pediatr Hematol Oncol. 2007; 29; Annaloro C et al. BMT. 2008; 41: Airaghil L et al. J Endocrinol Invest. 2011; 34:e6-e11.

17 Cardiovascular Risk Factors are undertreated after HSCT Cross sectional study on 258 long-term survivors after allogeneic HSCT (1-21 years since HSCT) metabolic syndrome in 49% 2.2 fold increase compared with controls Untreated patients hypertension in 25% abnormal fasting glucose in 17% dyslipidemia in 60% Majhail NS et al. et al. BMT. 2009; 12143; Number of persons with CV risk factors 44 long-term survivors (11-26 years post-transplant) treated untreated Hypertension 22 5 Dyslipidemia Rovó A. et al. Haematologica. 2011; 96:

18 Take home message Prevalence of cardiac and cardiovascular complications is still low Early and late heart complications are different and have different risk factors However, the magnitude of risk of late complications could greatly increase with longer follow-up Anthracyline is the main risk factor for late cardiomyopathy Pretransplant radiation and post-transplant appearance of cardiovascular risk factors are the main risk factors of coronary artery disease Cardiovascular risk factors after HSCT are undertreated No data on the effect of preventive measures It seams reasonable to treat early

19 Thank you for your attention