O Papel do TCH na LLC. Fábio R. Kerbauy

Transcription

1 O Papel do TCH na LLC Fábio R. Kerbauy

2 Outline Autologous SCT Allogeneic SCT Indications Mieloablative x non-myeloablative Brazilian experience

3 HCT Indications CIBMTR 2012 Pasquini MC, Wang Z. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides, Available at:

4 CLL Heterogeneity Foá R. et al. Haematologica 2013; 98:

5 P53 mutations

6 17p x HCT

7 Relapse after FCR: Survivall after salvage therapy

8 Fludarabine resistence

9 Allogeneic HCT in Flu refractary CLL Dreger et al. EBMT. 2007

10 Allogenic HCT indications Relapse (24 months after fludarabine treatment) p53 mutation (fullfiling criteria for treatment) Fludarabine refractary Multiples relapses

11 European Consensus HCT for CLL

12 NCCN

13 NCCN

14 Brazilian Consensus HCT for CLL Relapse (24 months after fludarabine treatment) p53 mutation (fullfiling creteria for treatment) Fludarabine refractary Multiple relapses

15 Survival after Autologous and HLA-matched Sibling Donor Hematopoietic Cell Transplants for CLL, CIBMTR Probability of Survival, % Autologous transplant (N=270) Myeloablative conditioning (N=450) Reduced-intensity conditioning (N=871) P < Years

16 EBMT : Auto x alo for CLL

17 Autologous x FC/Observation Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC Sutton L. et al. Blood 2011; 117(23)

18 GVL effect in CLL D+14 D+370 Schetelig J et al. JCO 2003;21: Hoogendoorn M et al. Leukemia 2007;21:

19 Conditioning regimens in CLL D+370 Delgado J et al. Blood 2009; 114(13)

20 Myeloablative for CLL MICHALLET (2003) DONEY (2002) PAVLETIC (2005) TOZE (2005) n Age (y) MRD (%) MUD (%) Conditioning TBI : 95% TBI : 68% TBI TBI : 50% TRM (%) (Bu-Cy) - 17 (TBI) OS 46% (3) 41,2% (10) 32% (5) 62% (5) 39% (5) DFS 36,6% (10) 30% (5) 39% (5)

21 RIC for CLL

22 Tópicos Intrudução Doadores de registro (Não aparentados) Sangue de cordão umbilical e placentário Haploidêntico

23 Patients Multicentric Retrospective analysis Allogeneic HCT for CLL Query to Transplantation Centers in Brasil

24 Patients Institution N Universidade Federal Paraná 10 UNIFESP 08 Hospital Amaral Carvalho 07 Santa Casa São Paulo/Samaritano 06 Hospital Santa Marcelina 05 UNICAMP 05 Hospital Sírio Libanês 03 Hospital do Câncer Goiás 02 Hospital Albert Einstein 02 TOTAL 48 From April/2000 to November/2013

25 Patients Age (years) 48,85 (24 70) Rai I-II III-IV Binet A B C 20(42%) 28(58%) 04(9%) 34(70%) 10(21%) N treatment before HCT > 2 31(65%) Time from Diagnosis to HCT (months) 35,9 (08 101) Refractory at transplant 14 (29%) Fludarabine treatment 38 (80%) Rituximab treatment 20 (40%)

26 Conditioning Regimens Mieloablative (16%) RIC / NMA (84%) Conditioning BuCy 04 CyTBI 03 Ara-c/CyFluTBI 01 (+/-Cy/R) FluTBI 09 FluMel 10 (+/-R) FluCy 14 FluBu 03 CyMel 04 N Post HCT Immunessupresion N MTX/CSA 27 MMF/CSA 13 Others 8

27 Graft source MRD/MUD 42(88%)/6 (12%) Peripheral blood Stem cell 45 (93%) CD34+ x 10⁶/Kg 5,6 (1,7 10,5) Engraftment (95%) D+14 (D+9 D+19)

28 Outcomes DLI response 04 / 04 TRM (100 dias) 13,3% TRM (1 year) 31% Acute GVHD (II-IV) 38% Chronic GVHD 43% OS (5y) 48.5% EFS (5y) 43%

29 Overall Survival

30 Non-Relapse Mortality

31 Conclusions Allogeneic HCT for CLL: possible curative approach Especially in Brazil High incidence of NRM even using RIC/NMA

32 HCT for CLL Curative : 50-80% Overcome poor-prognostic factors: genetic/clinical GVL is effective: non-myeloablative conditioning, DLI EARLY TRM: LOW (5%) TRM: up to 30% Quality of life: 25% chronic GVHD Richter? Pre-exposed to BCRinhib patients? BCRi/BCL2 x GVHD?

33 New era: novel agents x HCT HCT is the only pontentially curative therapy BCRi/BCL2a: most effective non-hct treatment. Cure is unlikely BCRi/BCL2 RESPONDERS: 2y survival 60-70% HCT 70-80% continuation on BCRi/BCL2 HCT: High risk-therapy 15-30% TRM 25% Chronic GVHD

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35 Ibrutnib after HCT

36 New era: novel agents x HCT

37 New era: novel agents x HCT Standard-risk: in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. High-risk: after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors.

38 Acknowledgement Unifesp/HSM Jose Salvador R. Oliveira Ana Marcela Rojas Santa Casa de SP/Samaritano Carlos Chiattone Ricardo Chiattone Jose C. Barros HIAE Nelson Hamerschlak Jairo J. N. Sobrinho Fabio Pires dos Santos Guilherme Perini Hosp Sirio Libanês Celso Arrais Rodrigues Univ. Federal Paraná Vaneuza Funke Hosp Câncer Goiás Adriano Moraes Arantes UNICAMP Afonso Vigoritto Hospital Brigadeiro Jose C Barros Hospital Amaral Carvalho

39 OBRIGADO!!