S117 THE ROLE OF ANTI‐THYMOCYTE GLOBULIN WITH THIOTEPA‐BUSULFAN‐FLUDARABINE BASED CONDITIONING IN PATIENTS UNDERGOING HAPLOIDENTICAL STEM CELL TRANSPLANT AND POST‐TRANSPLANT CYCLOPHOSPHAMIDE
Authors: El‐Cheikh J. , Devillier R. , Dulery R. , Massoud R. , Moukalled N. , Ghaoui N. , Pagliardini T. , Marino F. , Bazarbachi A. , Castagna L. , Mohty M. , Blaise D. 
Published: June 2019

Background:

TheThiotepa‐Busulfan‐Fludarabine (TBF) based conditioning regimen is widely used in T‐cell repleted haploidentical transplantation (Haplo) with post‐transplant cyclophosphamide. However, the use of Anti‐thymocyte globulin (ATG) has not been well established. It decreases the incidence of graft versus host disease however some claim that it's at the cost of increased relapse.

Aims:

Objectives:

We conducted this multi centric study to compare the outcomes of patients who underwent Haplo with TBF conditioning regimen with ATG to those without.

Methods:

this is a multicentric retrospective study. Data was collected from 4 centers, the American University of Beirut Medical Center, Hospital Saint Antoine Paris, institute Paoli Calmette Marseille, and Humanitas Research Hospital Milan. We included all consecutive adult patients who underwent Haplo with TBF conditioning. The conditioning consisted of thiotepa 5 mg/kg per day infused on days −7 and/or −6, fludarabine 30 mg/m2 infused on day −5 to day −2; and busulfan 130 mg/m2 infused on day −5 to day −3. Graft versus host disease (GVHD) prophylaxis consisted of post transplantation cyclophosphamide 50 mg/kg per day on day +3 and day +5, cyclosporine on day +6 and readjusted according to level, and mycophenolate mofetil 500 mg every 6 hours beginning on days +6 to +28[DR1] or +35 depending on the center. Patients who received ATG received a dose of 2.5 mg/kg per day.

Results:

We included a total of 268 patients, 69 of whom (26%) received ATG (group 2) as part of the conditioning chemotherapy. Patients who received ATG had a younger median age compared to the second group without ATG (group 1) (53 and 58 years respectively; p value 0.004). (63% vs 61%) of each group had acute leukemia, and (71% vs 70%) were in complete remission at the time of transplant, while 47 patients (24%) in the group 1 had progressive disease at transplant. 151 patients (56.5%) had an intermediate disease risk index (DRI). In the ATG group, 59 patients (30%) compared to 50 (73%) in the other group received 5 mg/kg Thiotepa, while 140 (70) and 19 (27%) received 10 mg/kg respectively. Peripheral blood stem cells were the most common graft source in both groups (83% and 88% respectively). At a median follow‐up of 15.4 months, patients receiving ATG had a statistically significant decreased risk of acute graft versus host disease (aGVHD) (RR 0.47; p value 0.031), and non‐relapse mortality (NRM) at 24 months (RR 0.5; p value 0.027). ATG also resulted in higher progression and overall survival at 24 months, which was not statistically significant (66.2% and 59.8%; p value 0.168, with 76.6% and 67.8%; p value 0.056 respectively)

Summary/Conclusion:

Conclusion:

ATG as part of the pre‐transplantation conditioning leads to significant reduction in aGVHD and NRM at 24 months without significant effects on PFS or OS.