Epidemiology of SAA according to age of the patients

Transcription

1 Aplastic anemia in the elderly André Tichelli University of Basel Switzerland Epidemiology of SAA according to age of the patients Incidence of aplastic anemia Overall incidence 2.34 per million inhabitants per year Distribution of the Swiss population in 1900 and 2010 Montané E. et al. Haematologica. 2012; 93:

2 Two treatment options improving over the decades Bone marrow transplantation ATG and Cyclosporine A SAA-EBMT registry, update July 2012 Influence of the severity of the disease Bone marrow transplantation ATG and Cyclosporine A SAA-EBMT registry, update July 2012 Tichelli A. et al. Blood 2011;117:

3 Influence of the age at first-line treatment Bone marrow transplantation ATG and Cyclosporine A SAA-EBMT registry, update July 2012 Tichelli A. et al. Blood 2011;117: HLA identical sibling BMT with standard conditioning: Cyclophosphamide 200mg/kg + ATG <=10 <=20 <=30 <=40 >40 0 GvHD p< rejection p<

4 Failure-free survival for patients treated first with IS or BMT Bacigalupo A. Sem. Hematol. 2000; (37) Failure free survival (%) according to severity and age of the patient Marsh J. Blood Review

5 Immunosuppression with ATG and CSA according to age Retrospective SAA-EBMT study Number of patients: 810 Treatment Survival at 5 years < 50 years 72% years 57% 60 years 50% No age difference for Response rate Relapse rate But higher death rate Tichelli A. Ann I Med. 1999; (130)

6 Standardized mortality ratio Observed to expected death rate < 50 years SMR years SMR years SMR 9.05 Comparison with general population Observed/expected death rate Standardized mortality ratio (SMR) Tichelli A. Ann I Med. 1999; (130) Outcome of patients 70 years of age treated between Age at IS N Survival 5 years <20 years ±4% years ±4% years ±8% >70 years 50 33±16% Time to death for patients >70 years 65 days (range ) Update 2005; Tichelli et al, unpublished data 6

7 Causes of death according to the age Causes < 60 years 60 years Total number p Number deaths 20 (15%) 24 (41%) Infections 9 (45%) 15 (63%) Non response/ relapse 6 (30%) 2 (8%) n.s. malignancies 1 (5%) 2 (8%) n.s. Cardiovascular disease 1 (5%) 3 (12%) TRM 3 (15%) 1 (4%) n.s. unknown 0 1 (4%) n.s. Based on data from the G-CSF study (Tichelli A. et al. Blood 2011;117: ) Survival according to severity between age groups years 60 years adults years EBMT SAA Study, additional data 7

8 Response to immunosuppression is independent of age However it is associated with increased early mortality ATG and CSA is the gold standard for immunosuppressive treatment ATG & CsA; 39% p = 0.04 ATG; 24% Frickhofen N et al. Blood. 2003; 101: YizhouZheng et al, Exp. Hematol. 2006; 34:

9 Immunosuppression with ATG and CSA compared to ATG alone, in younger adults Better event free survival Improved survival Faster improvement of the blood values More complete response No difference on relapse rate Need of hospitalization for both treatment forms Combination more toxic? Frickhofen N. Blood 2003 (101) Prospective randomized study comparing CSA alone versus ATG and CSA for non-severe aplastic anemia Parameter CSA N=61 ATG+CSA N=54 Response 28 (46%) 40 (74%).02 Hemoglobin Neutrophils Platelets 9.7 ( ) ( ) p ATG* 15 (25%) 3 (6%) Alive failure free 41 (67%) 49 (90%).001 Marsh J et al. Blood 1999; 93:

10 But Cyclosporine alone has similar overall survival is more convenient (outpatient treatment) patients not responding are re-treatable with ATG and CSA How to treat elderly patients with aplastic anemia Small retrospective single center study (Canada) 24 patients Median age, 70 years (61-78) Standard versus attenuated IS 50% dose reduction of ATG Immunosuppressive treatment Normal ATG+CSA (n=7) Reduced dose of ATG (n=13) CSA alone (n=4) Response Similar to what is expected No difference with attenuated IS Kao SY. Et al. Br J Heamtol. 2008; 142: Early death in 6/24 (25%) 3/7 standard dose 3/17 with attenuated dose Cardiac adverse events 4/24 patients Cardiac death (1) Arrhythmia (1) Congestive heart failure (2) 10

11 Is low dose ATG effective in the treatment of SAA? 14 patients with aplastic anemia 12 were evaluable Median age 71 years (62-74) 3 vsaa; 4 SAA; 7 NSAA; Treatment One third of the standard ATG dose No CSA Results Good tolerance of the treatment 2 deaths of infection 1 response at 6 months Conclusion Lower dose, well tolerated in the elderly However low efficacy Discrepancy between both studies due to additional CSA treatment? Killick S.B. et al. Leuk Research. 2006; 30: Danazol as first line therapy for aplastic anemia? Danazol n= males Age 51 (6-85) Median daily dose 400mg during 12 months Response rate 47% Median time to response 90 days (30-720) Jaime-Pérez J.C. et al. Ann Hematol. 2011; 90:

12 Less toxic treatment as well as the most efficient and most convenient treatment should be used In the inpatient setting Patients with high risk for severe infections (neutro <0.2 x10 9 /L) Presenting with severe infection needing a hospitalization Patients sensitized against platelet transfusion They need a rapid response And are anyway hospitalized ATG + CSA? In the outpatient setting Patients who are not at immediate risk of severe infection Patients who can be managed as outpatients with supportive care until response Thrombocytopenia is not per se a reason for hospitalization They may benefit of CSA treatment Patients not responding to CSA are retreat able with ATG + CSA Alternatives? Androgens, Danzol? Tichelli A and Marsh J. BMT. Press Severity of the disease and infectious complications The presence of co-morbidity The willingness of the patient and his family members to be treated 12

13 Transplantation in the elderly Patients with a syngeneic donor HSCT as first-line treatment Elderly patients refractory to immunosuppression HSCT is an option RIC conditioning TRM and OS is not increased in elderly patients treated with RIC for AML and MDS Mc Clune BL et al. JCO. 2010; 28: Patients with aplastic anemia Eligible for IS Comorbidities Willingness of patient yes no Best supportive care SAA/vSAA with severe neutropenia and/or severe infection Moderate AA with neutrophils >0.5 x10 9 /L without severe infection Patients with a syngeneic donor ATG + CSA CSA ± androgens Syngeneic BMT Non-responders still eligible for IS Tichelli A and Marsh J. BMT. in Press 13

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