A study found that residual myeloproliferative neoplasm clones persisted after hematopoietic cell transplantation in patients with myelofibrosis, and this information enabled researchers to identify three molecular features of relapse.
Nico Gagelmann, MD, of the Dana-Farber Cancer Institute, and colleagues presented the findings at the 2026 EHA Congress.
The study performed next-generation sequencing and quantified somatic variants in 43 genes before and after HCT from patients enrolled in a prospective, phase 2 trial. Among the cohort, 36 patients had screening samples, 27 had screening and day 100 samples, and 23 had month six or 12 or end of treatment samples. Median patient age was 64 years, and most (83%) had Dynamic International Prognostic Scoring System intermediate-2 or high-risk disease.
Before HCT, MPN phenotypic drivers included JAK2 (67%), CALR (17%), and MPL (11%). Most patients (86%) had additional myeloid driver mutations, and 67% had one or more high-molecular-risk (HMR) mutations.
The dominant molecular features of relapse were:
- TP53 mutations at baseline
- Persistent HMR mutations
- Emergent RAS/MAPK subclonal evolution
At day 100, 28% of JAK2 mutations were detectable, all below the 1% consensus remission threshold. Pre-HCT HMR mutation status was not associated with molecular persistence, and CALR and MPL persistence were not observed at any variant allele frequency.
Six patients had clinical relapse. In all patients (n=2/2; 100%) with pre-HCT TP53 mutations, relapses were enriched for SRSF2 and U2AF1 mutations compared with just 12% (n=4/34) of patients without TP53 mutation at baseline.
Five of the patients who relapsed had full chimerism at day 100, though detectable mutations were derived from the pre-HCT MPN clone in four of those patients, while one had a newly acquired PTPN11 mutation. Four of the patients who relapsed had relapse-persistent HMR mutations, and five had evidence of subclonal evolution, most commonly involving the RAS/MAPK pathway.
Most patients (70%) had new post-HCT DNMT3A and/or TET2 mutations that were not detected pre-HCT, which the authors said is consistent with donor-derived clonal hematopoiesis.
“Integrating high-sensitivity molecular monitoring into post-HCT surveillance could optimize MRD definition and prompt preemptive intervention in larger prospective trials,” the authors concluded.
Reference
Gagelmann N, Awais N, Hao R, et al. Measurable residual disease in myelofibrosis: clonal correlates from a prospective phase II study. Abstract #6772. Presented at the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden.
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