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Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are myeloid malignancies affecting older patients, who have historically often been considered ineligible for allogeneic stem cell transplantation (allo-SCT) due to their age and pre-existing comorbidities. However, reduced intensity conditioning (RIC) regimens have allowed more older patients to receive allo-SCT, often from older sibling donors.
The presence of preleukemic mutations in peripheral blood (PB) samples is termed clonal hematopoiesis of indeterminate potential (CHIP). CHIP is defined as the absence of definitive morphologic evidence of hematologic neoplasms, with the presence of a somatic mutation with a variate allele frequency (VAF) of > 2%. The incidence of CHIP increases with age and comes with an increased risk of developing myeloid malignancies and cardiovascular complications. Therefore, using older donors with CHIP may impact the outcomes of patients undergoing transplantation.
During the 61st meeting of the American Society of Hematology (ASH), Betul Oran, MD Anderson Cancer Center, Houston, US, presented the results from a study which evaluated the impact of donor clonal hematopoiesis on the risk of acute graft-versus-host disease (GvHD, aGvHD) and patient outcomes. The trial was conducted in patients with AML or MDS who received a transplant from a matched-related donor (MRD) aged 55 years or older.
CHIP positive
CHIP negative
HR
95% CI
p value
N
57
245
-
-
-
Relapse incidence (RI) at 5-years
Not reported (NR)
NR
0.9
0.5–1.5
0.7
Age-adjusted RI at 5-years
NR
NR
0.9
0.6–1.4
0.7
Progression incidence at 5-years, %
40
44
0.9
0.5–1.4
0.5
TRM at 6 months, %
12
9
1.6
0.5–4.9
0.4
Age adjusted RM at 6 months
NR
NR
1.3
0.6–2.9
0.5
PFS at 5-years, %
38
36
0.97
0.7–1.4
0.9
Age adjusted PFS at 5-years
NR
NR
0.96
0.7–1.4
0.8
OS at 5-years, %
43
41
1.05
0.7–1.5
0.8
CHIP positive
CHIP negative
HR
95% CI
p value
N
57
245
-
-
-
Grade II-IV aGvHD at 6 months
Total, %
51
27
2.1
1.4–3.3
0.001
Donor > 65 years, %
54
27
2.1
1.05–4.4
0.04
Donor ≤ 65 years %
48
28
2
1.1–3.5
0.001
Grade III-IV aGvHD at 6 months
Total, %
16
5
3.2
1.3–7.4
0.008
Donor > 65 years, %
17
7
2.4
0.6–9.5
0.2
Donor ≤ 65 years %
15
5
3.5
1.1–10
0.03
cGvHD at 5 years, %
23
35
0.65
0.4–1.2
0.2
In patients with AML or MDS receiving allo-SCT with PB stem cells from an older MRD as the source, donor CHIP was associated with a significant increase in grade II-IV and III-IV aGvHD. However, engraftment, risk of progression and OS were unaffected. Further studies are warranted in order to better understand the molecular mechanisms of aGvHD and to identify therapeutic interventions to improve CHIP donor-induced aGvHD.
References
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