All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit Know AML.
Introducing
Now you can personalise
your AML Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe AML Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the AML Hub cannot guarantee the accuracy of translated content. The AML Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The AML Hub is an independent medical education platform, sponsored by Daiichi Sankyo, Jazz Pharmaceuticals, Kura Oncology, Roche and Syndax and has been supported through a grant from Bristol Myers Squibb. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.
Bookmark this article
Measurable residual disease (MRD)-positive status prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased relapse incidence (RI) and reduced overall survival (OS) in patients with acute myeloid leukemia (AML). Testing MRD status prior to transplant may help assess a patient’s disease risk and predict outcome.1
Anti-thymocyte globulin (ATG) is able to effectively deplete T-cells in vivo and is often used to prevent graft-versus-host disease (GvHD) – a major cause of non-relapse mortality (NRM) post-allo-HSCT.2 Some studies have shown that the use of ATG is associated with improved transplant outcomes, however since ATG can eliminate alloreactive donor T-cells, it may also reduce the graft-versus-leukemia effect resulting in increased RI and reduced OS.1,3 There is also a particular concern that ATG may increase RI in patients who are MRD-positive. Therefore, the optimal setting where ATG can be used without impacting leukemia-free survival (LFS) is currently undetermined.1
To assess whether the use of ATG impacted post-transplant outcomes, specifically in relation to pre-transplant MRD status, Arnon Nagler, Bhagirathbhai Dholaria, Myriam Labopin, and colleagues conducted a retrospective analysis of patients with AML who underwent allo-HSCT in first complete remission (CR1), stratified by MRD status. The results were recently published in Leukemia and are summarized in this article.
Total cohort results are shown in Table 1.
aGvHD; acute graft-versus-host disease, allo-HSCT; allogeneic hematopoietic stem cell transplantation, cGvHD; chronic graft-versus-host disease, CI; confidence interval, LFS; leukemia-free survival, NRM; non-relapse mortality, OS; overall survival |
||
Factor |
% |
95% CI |
---|---|---|
Grade II–IV aGvHD in first 100 days post-allo-HSCT |
24 |
22.1–26.6 |
Two-year incidence of grade II–IV cGvHD |
38 |
34.6–40.4 |
Two-year incidence of extensive cGvHD |
20 |
17.6–23.0 |
Two-year NRM |
11 |
8.9–12.5 |
Two-year LFS |
62 |
59.3–65.0 |
Two-year OS |
62 |
59.3–65.0 |
Multivariate analysis was conducted to evaluate the individual effect of baseline patient and transplant characteristics on outcome measures. The impact of ATG on post-transplant patient outcome in MRD-negative patients is shown in Table 2. The use of ATG led to a reduced rate of grade II–IV acute GvHD (aGvHD), cGvHD and extensive GvHD whilst improving LFS, OS and GRFS and without impacting RI.
aGvHD; acute graft-versus-host disease, cGvHD; chronic graft-versus-host disease, CI; confidence interval, GRFS; GvHD-free relapse-free survival, LFS; leukemia-free survival, NRM; non-relapse mortality, OS; overall survival, RI; relapse incidence |
||||
Factor |
Effect |
HR |
95% CI |
P value |
---|---|---|---|---|
RI |
None |
0.80 |
0.59–1.1 |
0.17 |
Grade II–IV aGvHD |
Reduced |
0.71 |
0.51–0.99 |
0.04 |
Grade III–IV aGvHD |
Reduced |
0.37 |
0.20–0.66 |
<10-3 |
cGvHD |
Reduced |
0.55 |
0.41–0.72 |
<10-4 |
Extensive cGvHD |
Reduced |
0.42 |
0.27–0.64 |
<10-4 |
NRM |
Reduced |
0.66 |
0.43–1.0 |
0.05 |
LFS |
Improved |
0.74 |
0.58–0.95 |
0.02 |
OS |
Improved |
0.69 |
0.53–0.92 |
0.01 |
GRFS |
Improved |
0.62 |
0.50–0.77 |
<10-3 |
In MRD-positive patients, the use of ATG did not impact RI, but did lead to a reduction in the rate of cGvHD and extensive cGvHD (Table 3). NRM, LFS, OS and GRFS were unaffected by the use of ATG in this population of patients.
aGvHD; acute graft-versus-host disease, cGvHD; chronic graft-versus-host disease, CI; confidence interval, GRFS; GvHD-free relapse-free survival, LFS; leukemia-free survival, NR; not reported, NRM; non-relapse mortality, OS; overall survival, RI; relapse incidence |
||||
Factor |
Effect |
HR |
95% CI |
P value |
---|---|---|---|---|
RI |
None |
1.03 |
0.64–1.65 |
0.92 |
Grade II–IV aGvHD |
None |
0.89 |
0.53–1.50 |
0.66 |
Grade III–IV aGvHD |
Reduced |
0.58 |
0.22–1.48 |
0.25 |
cGvHD |
Reduced |
0.56 |
0.33–0.95 |
0.03 |
Extensive cGvHD |
Reduced |
0.4 |
0.20–0.80 |
0.01 |
NRM |
None |
0.55 |
0.21–1.46 |
0.23 |
LFS |
None |
0.93 |
0.61–1.42 |
0.74 |
OS |
None |
0.81 |
0.51–1.23 |
0.36 |
GRFS |
None |
0.87 |
0.61–1.24 |
0.43 |
In the regression analysis, other variables were found to be significantly associated with outcome. These are summarized below:
In patients with AML undergoing allo-HSCT in CR1, ATG use was found to reduce the risk of GvHD and did not increase RI, even in patients who were MRD-positive prior to transplant. In MRD negative patients the use of ATG was also associated with improved LFS, OS, and GRFS. The authors concluded that ATG should be incorporated into standard pre-transplant regimens for patients with AML, irrespective of MRD-status and conditioning regimen intensity.
Your opinion matters
Subscribe to get the best content related to AML delivered to your inbox