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THE ADDITION OF ATG TO NON-MYELOABLATIVE ALLOGENEIC STEM CELL TRANSPLANTATION WITH FLUDARABINE AND CYCLOPHOSPHAMIDE REDUCES GVHD AT THE EXPENSE OF HIGHER RELAPSE RATES AND POORER OVERALL SURVIVAL.
Author(s): ,
Mayani Rawicki
Affiliations:
ACRF Translational Research Laboratory,Royal Melbourne Hospital,Melbourne,Australia;Faculty of Medicine, Dentistry and Health Sciences,University of Melbourne,Melbourne,Australia
,
Ray M Koo
Affiliations:
ACRF Translational Research Laboratory,Royal Melbourne Hospital,Melbourne,Australia;Clinical Haematology,Peter MacCallum Cancer Centre–Royal Melbourne Hospital,Melbourne,Australia
,
Rachel Koldej
Affiliations:
ACRF Translational Research Laboratory,Royal Melbourne Hospital,Melbourne,Australia;Faculty of Medicine, Dentistry and Health Sciences,University of Melbourne,Melbourne,Australia
,
David Ritchie
Affiliations:
ACRF Translational Research Laboratory,Royal Melbourne Hospital,Melbourne,Australia;Faculty of Medicine, Dentistry and Health Sciences,University of Melbourne,Melbourne,Australia;Clinical Haematology,Peter MacCallum Cancer Centre–Royal Melbourne Hospital,Melbourne,Australia
Eric Wong
Affiliations:
ACRF Translational Research Laboratory,Royal Melbourne Hospital,Melbourne,Australia;Faculty of Medicine, Dentistry and Health Sciences,University of Melbourne,Melbourne,Australia;Clinical Haematology,Peter MacCallum Cancer Centre–Royal Melbourne Hospital,Melbourne,Australia;Department of Clinical Haematology,Austin Health,Melbourne,Australia
EHA Library. Rawicki M. 06/09/21; 324963; EP1243
Mayani Rawicki
Mayani Rawicki
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1243

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background
The use of anti-thymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis has been demonstrated to reduce acute GVHD (aGVHD) and chronic GVHD (cGVHD) following myeloablative HLA matched related and unrelated allogeneic stem cell transplantation (alloSCT). However, its use in non-myeloablative (NMA) alloSCT is less well described with concerns for graft loss or poor donor chimerism due to prolonged lymphocyte depleting effects.

Aims
To analyse the impact of ATG on post-transplant outcomes following unrelated donor alloSCT using NMA conditioning with fludarabine and cyclophosphamide

Methods
We reviewed patients treated at our centre that received alloSCT from an unrelated donor (n=58) between 2000 and 2020 with (n=35) or without ATG (n= 23) for the treatment of haematological malignancies. All patients received either fludarabine (90mg/m2) and low-dose cyclophosphamide (2250mg/m2) or fludarabine (125mg/m2) and high dose cyclophosphamide (120mg/kg). The primary outcomes were the incidence and severity of aGVHD, cGVHD and T-cell chimerism within the first 100 days following transplantation. Secondary outcomes included rates of non-engraftment, overall survival (OS), and GVHD-free relapse free survival (GRFS).

Results
The ATG cohort was older (median 59 vs 55 years) with more female participants (48.6% vs 30.4%) but had similar disease characteristics and conditioning to the non-ATG group. All patients engrafted with faster neutrophil and platelet engraftment in the ATG cohort with a median recovery time of 16 days (range: 8-23) vs 19 days (range: 9-34) [P = 0.03] and 18 days (range: 10-35) vs 20 days (range: 8-33) [P = 0.47] respectively. There was no difference in median T-cell chimerism at day 30, 60 or 100 for either group although more patients in the ATG cohort had chimerism less than 50% (37.1 vs 17.4%, p = 0.080) at day 100. At 80 months follow-up post-transplant, the cumulative incidence (CI) of cGVHD (0.20 vs 0.52; P = 0.0076) and moderate to severe cGVHD (0.11 vs 0.35; P = 0.048) was lower in the ATG cohort however there was a higher incidence of relapse (0.60 vs 0.17; P = 0.015). There were no significant differences in the incidence of aGVHD (0.20 vs 0.26; P = 0.53) or non-relapse mortality (0.14 vs 0.087; P = 0.50). OS for the ATG group was significantly lower (42.9% vs 82.6%; P = 0.0026), with a lower relapse free survival (25.7% vs 73.9%, P = 0.12) and GRFS (20% vs 48.9%, P = 0.69). 

Conclusion
The addition of ATG to NMA conditioning alloSCT with fludarabine and cyclophosphamide was associated with a reduced incidence of GVHD but with no significant difference in T-cell chimerism or engraftment. There was a greater likelihood of disease relapse leading to inferior OS with the use of ATG. 

Keyword(s): ATG, Chimerism, Graft-versus-host disease (GVHD), Reduced intensity transplantation

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1243

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background
The use of anti-thymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis has been demonstrated to reduce acute GVHD (aGVHD) and chronic GVHD (cGVHD) following myeloablative HLA matched related and unrelated allogeneic stem cell transplantation (alloSCT). However, its use in non-myeloablative (NMA) alloSCT is less well described with concerns for graft loss or poor donor chimerism due to prolonged lymphocyte depleting effects.

Aims
To analyse the impact of ATG on post-transplant outcomes following unrelated donor alloSCT using NMA conditioning with fludarabine and cyclophosphamide

Methods
We reviewed patients treated at our centre that received alloSCT from an unrelated donor (n=58) between 2000 and 2020 with (n=35) or without ATG (n= 23) for the treatment of haematological malignancies. All patients received either fludarabine (90mg/m2) and low-dose cyclophosphamide (2250mg/m2) or fludarabine (125mg/m2) and high dose cyclophosphamide (120mg/kg). The primary outcomes were the incidence and severity of aGVHD, cGVHD and T-cell chimerism within the first 100 days following transplantation. Secondary outcomes included rates of non-engraftment, overall survival (OS), and GVHD-free relapse free survival (GRFS).

Results
The ATG cohort was older (median 59 vs 55 years) with more female participants (48.6% vs 30.4%) but had similar disease characteristics and conditioning to the non-ATG group. All patients engrafted with faster neutrophil and platelet engraftment in the ATG cohort with a median recovery time of 16 days (range: 8-23) vs 19 days (range: 9-34) [P = 0.03] and 18 days (range: 10-35) vs 20 days (range: 8-33) [P = 0.47] respectively. There was no difference in median T-cell chimerism at day 30, 60 or 100 for either group although more patients in the ATG cohort had chimerism less than 50% (37.1 vs 17.4%, p = 0.080) at day 100. At 80 months follow-up post-transplant, the cumulative incidence (CI) of cGVHD (0.20 vs 0.52; P = 0.0076) and moderate to severe cGVHD (0.11 vs 0.35; P = 0.048) was lower in the ATG cohort however there was a higher incidence of relapse (0.60 vs 0.17; P = 0.015). There were no significant differences in the incidence of aGVHD (0.20 vs 0.26; P = 0.53) or non-relapse mortality (0.14 vs 0.087; P = 0.50). OS for the ATG group was significantly lower (42.9% vs 82.6%; P = 0.0026), with a lower relapse free survival (25.7% vs 73.9%, P = 0.12) and GRFS (20% vs 48.9%, P = 0.69). 

Conclusion
The addition of ATG to NMA conditioning alloSCT with fludarabine and cyclophosphamide was associated with a reduced incidence of GVHD but with no significant difference in T-cell chimerism or engraftment. There was a greater likelihood of disease relapse leading to inferior OS with the use of ATG. 

Keyword(s): ATG, Chimerism, Graft-versus-host disease (GVHD), Reduced intensity transplantation

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