POST-TRANSPLANTATION CYCLOPHOSPHAMIDE VS. ANTITHYMOCYTE GLOBULIN AS GVHD PROPHYLAXIS FOR MISMATCHED UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION
Author(s): ,
Charlotte Nykolyszyn
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Angela GRANATA
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Thomas PAGLIARDINI
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Luca CASTAGNA
Affiliations:
HEMATOLOGY,Humanitas Cancer Center,ROZZANO,Italy
,
Samia HARBI
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Reda BOUABDALLAH
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Norbert VEY
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France;Aix-Marseille Univ, CNRS, INSERM, CRCM,MARSEILLE,France
,
Sabine FÜRST
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Valerio MAISANO
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Faezeh LEGRAND
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Claude LEMARIE
Affiliations:
Cell therapy facility,Paoli Calmettes Institute,MARSEILLE,France;CIC biothérapies: Inserm CBT-1409,MARSEILLE,France
,
Boris CALMELS
Affiliations:
Cell therapy facility,Paoli Calmettes Institute,MARSEILLE,France;CIC biothérapies: Inserm CBT-1409,MARSEILLE,France
,
Christian CHABANNON
Affiliations:
Cell therapy facility,Paoli Calmettes Institute,MARSEILLE,France;Aix-Marseille Univ, CNRS, INSERM, CRCM,MARSEILLE,France;CIC biothérapies: Inserm CBT-1409,MARSEILLE,France
,
Pierre-Jean WEILLER
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France
,
Didier BLAISE
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France;Aix-Marseille Univ, CNRS, INSERM, CRCM,MARSEILLE,France
Raynier DEVILLIER
Affiliations:
HEMATOLOGY,Paoli Calmettes Institute,MARSEILLE,France;Aix-Marseille Univ, CNRS, INSERM, CRCM,MARSEILLE,France
EHA Library. Nykolyszyn C. Jun 15, 2019; 267180; PS1563
Charlotte Nykolyszyn
Charlotte Nykolyszyn
Contributions
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Abstract

Abstract: PS1563

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
HLA-mismatched unrelated donor (MMUD) allo-HSCT can be associated with worse outcome compared with HLA-matched unrelated donor (MUD) allo-HSCT, notably because of a higher incidence of graft-versus-host disease (GVHD). GVHD prophylaxis based on high dose post-transplant cyclophosphamide (PT-Cy) was reported as highly efficient in the setting of haploidentical allo-HSCT. However, it is not known if that statement still stands true in the setting of MMUD allo-HSCT, for which antithymocyte globulin (ATG) is considered as a conventional GVHD prophylaxis.

Aims
The objective is to compare the efficacy of PT-Cy vs. ATG as GVHD prophylaxis for MMUD allo-HSCT in a single center retrospective study.

Methods
We selected for analysis all consecutive patients who underwent MMUD allo-HSCT using peripheral blood stem cell (PBSC) as graft source. Since 2015, 22 patients underwent MMUD allo-HSCT with PT-Cy (50 mg/kg/day on day+3 and day+4). Additional GVHD prophylaxis was a combination of cyclosporine A and mycophenolate mofetil. We compared their outcome with a historical cohort of the 40 consecutive patients who received MMUD allo-HSCT with ATG between 2010 and 2014.

Results

There was no significant difference in the baseline patient and transplantation characteristics between PT-Cy and ATG groups, except a significantly higher proportion of patients in the PT-Cy who underwent allo-HSCT without criteria for complete remission (41% vs. 6%, p=0.048).

The cumulative incidence of day-100 grades 2-4 and 3-4 acute GVHD were significantly lower in the PT-Cy group, none of them developing grade 3-4 acute GVHD (grade 2-4, PT-Cy vs. ATG: 14% vs. 35%, p=0.015; grade 3-4, PT-Cy vs. ATG: 0% vs. 18%, p=0.018, Fig1A). This was confirmed by multivariate analysis (HR=0.21, 95%CI=(0.05-0.80), p=0.022). However, we did not observe significant difference in the cumulative incidence of chronic GVHD in both univariate and multivariate analysis. The cumulative incidence of non-relapse mortality (NRM) at 1 year was 5% and 22% in the PT-Cy and ATG groups, respectively (p=0.107). This trend became significant once the risk of NRM was adjusted in multivariate analysis (HR=0.09; 95%CI=(0.01-0.85); p=0.035).

Interestingly, the decrease in GVHD incidence in the PT-Cy group was not associated with a significant increase in disease progression (1-year relapse incidence, PT-Cy vs. ATG: 10% vs. 27%, p = 0.063). Once adjusted in multivariate model, we observed significantly lower risk of relapse in the PT-Cy group (HR = 0.18; 95%CI =(0.04-0.88); p = 0.034). Finally, we observed significantly better 1-year PFS (PT-Cy vs. ATG: 86% vs. 50%, p=0.007; HR 0.15, 95%CI =(0.04-0.52); p=0.003), OS (PT-Cy vs. ATG: 88% vs. 62%, p=0.027, Figure 1C; HR 0.17, 95%CI=(0.04-0.78); p=0.022) and GRFS (PT-Cy vs. ATG: 70% vs. 30%, p = 0.012, Figure 1D; HR 0.33, 95%CI=(0.14-0.76); p=0.009) in the PT-Cy group.

Conclusion
We conclude that PT-Cy is an effective GVHD prophylaxis in the setting of MMUD allo-HSCT using PBSC, and seems associated with lower incidence of acute GVHD and better outcome compared with standard GVHD prophylaxis with ATG. This may suggest that as it was shown in the setting of haploidentical allo-HSCT, the use of PT-Cy can overcome the impact of HLA disparity, leading to promising survivals that approaches those observed after HLA matched allo-HSCT.

Session topic: 22. Stem cell transplantation - Clinical

Keyword(s): Cyclophosphamide, Graft-versus-host disease (GVHD), Unrelated donor stem cell transplant

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