Antithymocyte Globulin and Role Of Stem Cell Source On Outcome In Myeloablative Conditioning Of Allogeneic Hematopoietic Stem Cell Transplantation With Identical Sibling and Matched Unrelated Donors - A Retrospective Study Of French Society Of Bone Marrow Graft Transplantation and Cellular Therapy -
Authors: Ravinet Aurélie , Cabrespine Aurélie , Peffault de la Tour Regis , Michallet Mauricette , Yakoub-Agha Ibrahim , Milpied Noel-Jean , Deconinck Eric , Huynh Anne , Nguyen Stéphanie , Chevallier Patrice , Guilhot Francois , Leprêtre Stéphane , Bernard Marc , Fegueux Nathalie , Mohty Mohamad , Socie Gerard , Bay Jacques-Olivier 
Published: October 2019

Abstract

Objectives
Allogeneic hematopoietic stem cell transplantation (AHSCT) is an effective treatment modality for a number of hematological malignancies. Several retrospective studies demonstrate that the addition of antithymocyte globulin (ATG) to standard GvHD prophylaxis in myeloablative conditioned AHSCT resulted in a reduction of the incidence of acute and chronic GvHD. However the impact of rabbit ATG incorporated within a standard myeloablative conditioning regimen (MAC) prior to AHSCT on overall survival (OS) has never been clearly assessed. The purpose of this study is to evaluate retrospectively the long term influence of ATG on OS in a large cohort.

Methods
All AHSCT with matched sibling donor (MSD) and matched unrelated donor (MUD) performed between 2001-2010 in France and reported to Promise database were retrospectively studied. Patients fulfilling the requirements for this study had received a MAC such as total body irradiation (TBI)-cyclophosphamide or busulfan-cyclophosphamide (Bu-Cy) with or without ATG.

Results
1980 AHSCT were reported in 32 transplant centers. One hundred and fifty (8%) patients received ATG (25 with MSD and 125 with MUD), whereas 1830 (92%) did not receive ATG (1441 with MSD and 389 with MUD). Diagnosis were 1452 acute leukemia (73%), 340 myelodysplasia (MDS) and/or myeloproliferative syndrome (MPS) (17%), 157 lymphoma (8%), 9 myeloma and 21 chronic lymphocytic leukemia (CLL) (2%). 1385 patients received a TBI 12 Gy based regimen with cyclophosphamide whereas 595 patients received Bu-Cy. Bone marrow (1468 patients) or peripheral blood stem cells (512 patients) were infused 24-48h after the last cyclophosphamide administration (day 0). Median age at transplantation was 37.5 years in the ATG group and 39.2 years in the non ATG group. Median follow-up was of 79.8 months [19.2-138.8]. Using multivariable analysis, OS was adversely significantly influenced by age of recipient older than 39.1 years, bone marrow stem cell source, MUD, non-complete remission status before HSCT, GvHD grade 2-4, age of donor older than 38.3 years and the use of GvHD prophylaxis other than cyclosporine and methotrexate. ATG was not an independent variable influencing OS. The use of different model of multivariate analyses including propensity score trends to demonstrate that the influence of ATG on OS remain strongly correlated to donor type (MSD vs MUD). According to our results, patient with MSD presented better OS (not reached) than patient with MUD (37 months) (p<0.01). Interestingly, OS rates were lower in the ATG group compared to the non ATG group for patients who received bone marrow (median OS 81 months vs 112 months p=0.033). In this group, in the long term, patients who received ATG trend to have more relapse (median PFS 22 months vs 69 p=0.015). This difference is not observed for patient who received peripheral blood (PB), probably because PB induces more GvHD (49% vs 41%, p=0.001), which is usually correlated with less relapse. In this group, the use of ATG or not has no impact on OS.

Conclusion
The use of ATG does not influence OS. However, this use is strongly influenced by stem cell source with a negative impact of ATG for the group of patients who received BM. Its usefulness should be discussed.

Disclosures:
No relevant conflicts of interest to declare.