EBMT Complications and Quality of Life Working Party Educational Course

Transcription

1 EBMT Complications and Quality of Life Working Party Educational Course Organisers: R. Duarte, G. Basak October 2014, Warsaw, Poland #EBMT2014

2 EBMT Complications and Quality of Life Working Party Educational Course Influence of the conditioning regimen in the outcome of dual umbilical cord blood transplant (DUCBT) Alejandro Vázquez Ramo Hospital Universitario Puerta de Hierro Majadahonda (Madrid) October 2014, Warsaw, Poland 2 2

3 EBMT Complications and Quality of Life Working Party Educational Course Unrelated cord blood (CB) is now considered as one of the front line sources for patients in need for allogeneic stem cell transplantation without access to a suitable donor. (DUCBT): dual or haplo-cord Infusion of a single CB unit + mobilized CD34+ selected peripheral blood stem cells from an HLA-mismatched third party donor (TPD). Reduce the post-transplant period of neutropenia reducing early infection mortality and allowing using units with relatively low cell content October 2014, Warsaw, Poland 3 3

4 Dual umbilical CB transplant TPD UCB Neutrophils Conditioning regimen Temporaly engrafment of the TPD, reducing neutropenia period. Fernández et al: Experimental Hematology 2003; 31: Fernández et al: Haematologica 2006; 9:640-8 Bautista et al: Bone Marrow Transplantation; 2009; 43(5):365-73

5 Conditioning regimen Multiple different factors influence the outcome of DUCBT, being the conditioning regimen one of those more relevant. Due to lack of prior evaluation of its influence in our DUCBT strategy, we planned to analyze the outcome of our patients regarding their conditioning regimen. 5 5

6 Conditioning regimen The patients received myeloablative conditioning regimen with low extra-hematological toxicity. CD x10 6 /kg CNT >1.2x10 7 /kg CD3+ < 1x10 4 /kg CD34+ > 5-6 x 10 4 kg 6 6

7 CB cells were infused on day 0 followed by the TPD cells. As graft versus host disease prophylaxis, patients received cyclosporine (CsA) or tacrolimus from day -5 and metilprednisolone 1 mg/kg from day +1, tapered until suspension from day +10 to +14. In the absence of GvHD CsA or tacrolimus was tapered when full CB engrafment was achieved or from day

8 Patients and methods We included for evaluation consecutive DUCBT patients treated in 3 spanish transplant institutions until December transplants, 134 patients. We analysed retrospectively the outcome of our patients according to the use of TBI or busulfan (Chemo) in the conditioning regimen. 8 8

9 TBI vs Busulfan: results The TBI group included younger patients (median 32 vs 41 years) and more ALL patients (31 vs 11). The CHEMO group had more AML patients (38 vs 20). 9 9

10 TBI vs Busulfan: Results There were no differences in CD34+ cells/kg or TNC/kg contained in the UCB (median 0.14 x10 6 and 2.4 x10 7 respectively)

11 Engrafment Time to neutrophil (ANC) and platelet engraftment were not different between both groups

12 Graft failure Global graft failure incidence was low (5%) but it was higher in the CHEMO group (7% vs 2%)

13 Acute GVHD Acute GVHD grades II-IV was similar in both groups, but grade III-IV affected more the TBI group (8.3 % vs 1.4%), causing death in 4 cases

14 TRM P= % 24% TBI CHEMO 1 year-trm was higher for the TBI group (45% vs 24%) 14 14

15 Cumulative incidence Relapse 1,00 0, ,50 0,25 26% CHEMO p= ,00 15% months TBI Cumulative incidence of relapse (CIR) was lower in the TBI group (15% vs 27%) 15 15

16 OS and DFS OS DFS Rendering similar DFS and OS at 5y (39% vs 41% and 44 % vs 49%, for TBI and CHEMO groups respectively)

17 Supervivencia acum AML/MDS subgroup OS 1,0 0,8 57% CHEMO RT p= 0.11 NO SI NO-censurado SI-censurado 0,6 0,4 50% TBI 0,2 0, In the subgroup of AML/MDS patients meses_sup (n=71: TBI: 21; CHEMO: 50) subtle but non significant differences in DFS (44% vs 53%) and in OS (50% vs 57%) favour the CHEMO group

18 CONCLUSIONS With the limitations of a retrospective analysis and patient selection bias between the groups, global results seem similar between TBI and CHEMO groups in our DUCBT platform. Lower relapse and graft failure favour TBI use, but higher TRM penalize its results. Further strategies directed to reduce TRM are needed in this context to improve DUCBT results