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. 2024 Jul 23;8(14):3849-3858.
doi: 10.1182/bloodadvances.2023011761.

Recipient clonal hematopoiesis in allogeneic bone marrow transplantation for lymphoid malignancies

Philip H Imus  1 , Sergiu Pasca  1 , Hua-Ling Tsai  1 , Yosra M Aljawai  1   2 , Kenneth R Cooke  1 , Jeremy D Walston  1   3 , Christopher D Gocke  1 , Ravi Varadhan  1 , Richard J Jones  1 , Lukasz P Gondek  1
Affiliations

Recipient clonal hematopoiesis in allogeneic bone marrow transplantation for lymphoid malignancies

Philip H Imus et al. Blood Adv. .

Abstract

Allogeneic blood and marrow transplantation (alloBMT) is increasingly being used in older patients with blood cancer. Aging is associated with an increasing incidence of clonal hematopoiesis (CH). Although the effects of donor CH on alloBMT has been reported, the impact of recipient CH on alloBMT outcomes is unknown. In this retrospective study, alloBMT recipients age 60 and older with lymphoid malignancies were included. Among 97 consecutive patients who received alloBMT between 2017 and 2022, CH was detected in 60 (62%; 95% confidence interval [CI], 51-72). CH was found in 45% (95% CI, 28-64) of patients aged 60 to 64, 64% (95% CI, 44-81) of patients aged 65% to 69%, and 73% (95% CI, 59-87) in those above 70. Pretransplant CH was associated with worse survival after alloBMT: 3-year overall survival (OS) was 78% (95% CI, 65-94) for patients without CH vs 47% (95% CI, 35-63) for those with CH, (unadjusted HR, 3.1; [95% CI, 1.4-6.8; P < .001]). Nonrelapse mortality (NRM) was higher in patients with CH; cumulative incidence of NRM at 1-year was 11% (95% CI, 1-22) vs 35% (95% CI, 23-48), (HR, 3.4; [95% CI, 1.4-8.5], P = .009]). Among CH patients, worse OS and NRM was associated with CH burden and number of mutations. Recipient CH had no effect on relapse. In conclusion, older patients with CH experience worse outcomes after alloBMT, almost exclusively attributable to increased NRM. CH is a strong, independent predictor of outcomes. Novel strategies to ameliorate the adverse impacts of patient CH on transplant outcomes are being evaluated.

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Conflict of interest statement

Conflict-of-intreset disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Prevalence and characteristics of CH according to age of alloBMT recipient. (A) Distribution of CH mutations in the cohort. (B) Prevalence of CH at different ages. (C) Distribution of CH proportion according to patient age.
Figure 2.
Figure 2.
Clinical outcomes after alloBMT are associated with VAF pretransplant CH. Kaplan-Meier curves of (A) OS and (B) PFS; cumulative incidence of (C) NRM and (D) relapse by CH-negative or CH-positive. Estimates in CH positive group were further stratified by ([VAF] 1%-10% and ≥10%).
Figure 3.
Figure 3.
Clinical outcomes after alloBMT are associated with number of CH mutations with variant allele frequencies >1%. Kaplan-Meier curves of (A) OS and (B) PFS; cumulative incidence of (C) NRM and (D) relapse by CH-negative and number of mutations (single mutation, 2 or more mutations).
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Comment in

  • Soiled soil.
    Appelbaum FR. Appelbaum FR. Blood Adv. 2024 Jul 23;8(14):3847-3848. doi: 10.1182/bloodadvances.2024013145. Blood Adv. 2024. PMID: 39042383 Free PMC article. No abstract available.

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