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. 2022 Oct;57(10):1615-1619.
doi: 10.1038/s41409-022-01762-y. Epub 2022 Jul 27.

Pattern of somatic mutation changes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Sanghee Hong  1 , Lisa Rybicki  2 , Carmelo Gurnari  3   4 , Simona Pagliuca  3   5 , Aiwen Zhang  6 , Dawn Thomas  6 , Valeria Visconte  3 , Jibran Durrani  7 , Ronald M Sobecks  8 , Matt Kalaycio  8 , Aaron T Gerds  8 , Hetty E Carraway  8 , Sudipto Mukherjee  8 , Mikkael A Sekeres  9 , Anjali S Advani  8 , Navneet S Majhail  10 , Betty K Hamilton  7 , Bhumika J Patel  8 , Jaroslaw P Maciejewski  11   12
Affiliations

Pattern of somatic mutation changes after allogeneic hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes

Sanghee Hong et al. Bone Marrow Transplant. 2022 Oct.
No abstract available

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Figures

Figure 1.
Figure 1.. Pre-transplant factors associated with relapse-free survival at 5 years after transplant
Mutations that were unevaluable due to 0% or 100% presence were not listed. From multivariable analysis, age at transplant and number of mutation present before transplant were associated with 5-year RFS.
Figure 2.
Figure 2.. Relapse after allogeneic transplant
(A) Estimated probability of achieving RFS5 based on number of mutations and age at BMT. (B) Frequency of selected somatic mutations and cytogenetic abnormalities at diagnosis. *DNMT3A was the most commonly mutated genes in both post-transplant relapses (29%) and post-chemotherapy relapses (37%). DNMT3A mutations were less frequently seen in cases with 5-year RFS post BMT (4% vs. 29% in BMT rel, P=0.028). †25% (n=1 in early BMT relapse) and 50% (n=1) of baseline FLT3 mutations were internal tandem duplication (ITD) at BMT and chemotherapy relapses, respectively. ‡IDH1 mutations were enriched in relapses post BMT than those post-chemotherapy (14% vs. 0%, P=0.038) while §PCLO mutations were seen more often at chemotherapy relapses (11% vs. 0%, P=0.027). ∥Presence of PHF6 mutations was registered more often at late (18%) than early relapse (0%, P=0.037). (C) Changes in average variant allelic frequency (VAF) for each positive mutation. *Gain of BCOR and TP53 mutations were seen at BMT relapse than chemotherapy relapse (BCOR +91% at BMT relapse vs. −59% at chemotherapy relapse, P=0.011; TP53 +74% at BMT relapse vs. −62% at chemotherapy relapse, P=0.004). †There were more VAF increase of EP300 at early relapse (+9%) than at late relapse (−7%, P=0.003). §The greater decrease in VAF of IDH1 was seen with late relapses (−1%) than in early relapse (−41%, P=0.033). Overall, ǂ3% of chemotherapy (n=1), 6% of early transplant (n=2), and 12% of late transplant relapses (n=2) were seen with FLT3-ITD subclonal gain (P=0.48). Morover, 3%, 3%, and 6% of chemotherapy (n=1), early (n=1), and late transplant relapses (n=1) were seen with FLT3-ITD subclonal loss, respectively (P=0.84). (D) Overall molecular changes at relapse. Top = pattern of somatic mutation changes at relapses after BMT and after chemo. Middle= Somatic mutations before and after relapses (rel). A lower number of mutations was found in transplanted patients surviving without relapse. Also, patients who relapsed from chemotherapy had higher number of mutations before treatment than those who relapsed after transplant. Bottom = Subclonal gains and losses of individual mutations at relapse. A two-sample t-test was used for statistical comparisons. (E) VAF changes in selected 6 most positive gene mutations: ASXL1, DNMT3A, FLT3, NPM1, RUNX1, and TET2 (alphabetical order). Grey = reappearance, green =subclonal gain, pink =subclonal loss.
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References

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