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.

Table 1. Impact of CHIP on transplant outcomes

CHIP positive

CHIP negative

HR

95% CI

p value

N

57

245

-

-

-

Relapse incidence (RI) at 5-years

Not reported (NR)

NR

0.9

0.51.5

0.7

Age-adjusted RI at 5-years

NR

NR

0.9

0.61.4

0.7

Progression incidence at 5-years, %

40

44

0.9

0.51.4

0.5

TRM at 6 months, %

12

9

1.6

0.54.9

0.4

Age adjusted RM at 6 months

NR

NR

1.3

0.62.9

0.5

PFS at 5-years, %

38

36

0.97

0.71.4

0.9

Age adjusted PFS at 5-years

NR

NR

0.96

0.71.4

0.8

OS at 5-years, %

43

41

1.05

0.71.5

0.8

Table 2. Impact of donor CHIP on rates of GvHD

CHIP positive

CHIP negative

HR

95% CI

p value

N

57

245

-

-

-

Grade II-IV aGvHD at 6 months

Total, %

51

27

2.1

1.43.3

0.001

Donor > 65 years, %

54

27

2.1

1.054.4

0.04

Donor 65 years %

48

28

2

1.13.5

0.001

Grade III-IV aGvHD at 6 months

Total, %

16

5

3.2

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ASH 2019 | The impact of donor clonal hematopoiesis on aGvHD and patient outcomes - AML Global Portal