Long term results of the phase III study were published. They confirm 
our practice in  our Tx center

Presenter: Prof. Spyridondis
Particpants: Dr Liga, Dr Spyridis, Dr Verigou

Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic 
haemopoietic peripheral blood stem-cell transplantation from 
HLA-identical siblings in patients with acute myeloid leukaemia in 
remission: final results of quality of life and long-term outcome 
analysis of a phase 3 randomised study.
Lancet Haematol. 2019 Feb;6(2):e89-e99. doi: 
10.1016/S2352-3026(18)30214-X.

Abstract
BACKGROUND:
We previously showed that human anti-T-lymphocyte globulin (ATLG) plus 
ciclosporin and methotrexate given to patients with acute leukaemia in 
remission, having allogeneic haemopoietic stem-cell transplantation with 
peripheral blood stem cells from an HLA-identical sibling donor after 
myeloablative conditioning, significantly reduced 2-year chronic 
graft-versus-host disease (cGVHD) incidence and severity, without 
increasing disease relapse and infections, and improves cGVHD-free and 
relapse-free survival (cGRFS). The aim of an extended follow-up study 
was the assessment of long-term outcomes, which are, in this context, 
scarcely reported in the literature. We report unpublished data on 
quality of life (QoL) from the original study and the results of a 
follow-up extension.

METHODS:
In the original open-label study, patients with acute myeloid and 
lymphoblastic leukaemia in first or subsequent remission, having sibling 
HLA-identical allogeneic peripheral blood stem-cell transplantation, 
were randomly assigned (1:1) to receive ATLG plus standard GVHD 
prophylaxis with ciclosporin and short-term methotrexate (ATLG group) or 
standard GVHD prophylaxis without ATLG (non-ATLG group). Conditioning 
regimens were cyclophosphamide 120 mg/kg with either total body 
irradiation (12 Gy) or busulfan (12·8 mg/kg intravenously or 16 mg/kg 
orally), with or without etoposide (30-60 mg/kg). Randomisation was 
stratified according to centre and disease risk. The primary endpoint 
was cumulative incidence of cGVHD at 2 years. The primary and secondary 
endpoints, excluding QoL, have been published. QoL, assessed using 
European Organisation for Research and Treatment of Cancer QLQ-C30 and 
QLQ-HDC29 questionnaires, was an unpublished secondary endpoint, which 
we now report here. A follow-up extension was then done, with the 
primary endpoint cumulative incidence of cGVHD. Enrolment has been 
completed for both studies. The original trial (number, NCT00678275) and 
follow-up extension (number, NCT03042676) are registered at 
ClinicalTrials.gov.

FINDINGS:
In the original study, from Dec 14, 2006, to Feb 2, 2012, 161 patients 
were enrolled and 155 were randomly assigned to either the ATLG group 
(n=83) or to the non-ATLG group (n=72). In the follow-up study, which 
started on Feb 7, 2017, and was completed on June 30, 2017, 61 patients 
were included in the ATLG group and 53 were included in the non-ATLG 
group. Global health status showed a more favourable time course in the 
ATLG group compared with the non-ATLG group (p=0·02; treatment by visit 
interaction). ATLG was descriptively superior to non-ATLG at 24 months 
for physical function (points estimate -14·8 [95% CI -26·4 to -3·1]; 
p=0·014) and social function (-19·1 [-38·0 to -0·2]; p=0·047), 
gastrointestinal side-effects (8·8 [2·5-15·1]; p=0·008) and effect on 
family (13·5 [1·2-25·8]; p=0·032). Extended follow-up (median 5·9 years 
[IQR 1·7-7·9]) confirmed a lower 5-year cGVHD incidence (30·0% [95% CI 
21·4-41·9] vs 69·1% [59·1-80·1]; analysis for entire follow-up, 
p<0·001), no increase in relapses (35·4% [26·4-47·5] vs 22·5% 
[14·6-34·7]; p=0·09), improved cGRFS (34·3% [24·2-44·5] vs 13·9% 
[7·1-22·9]; p=0·005), and fewer patients still in immunosuppression 
(9·6% vs 28·3%; p=0·017) in the ATLG group compared with the non-ATLG 
group. 5-year overall survival, relapse-free survival, and non-relapse 
mortality did not differ significantly between groups.

INTERPRETATION:
The addition of ATLG to standard GVHD prophylaxis improves the 
probability of surviving without disease relapse and cGVHD after 
myeloablative peripheral blood stem-cell transplantation from an 
HLA-identical sibling donor for patients with acute leukaemia in 
remission. Further additional benefits are better QoL and shorter 
immunosuppressive treatment compared with standard GVHD prophylaxis 
without ATLG. Therefore, in this setting, ATLG plus standard GVHD 
prophylaxis should be preferred over the standard GVHD prophylaxis 
alone.