Mutation Clearance after Transplantation for Myelodysplastic Syndrome.

[title]

Mutation Clearance after Transplantation for Myelodysplastic Syndrome.

[author]

Duncavage EJ, et al. N Engl J Med. 2018.
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[Abstract]
BACKGROUND: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome (MDS). The molecular predictors of disease progression after transplantation are unclear.

METHODS: We sequenced bone marrow and skin samples from 90 adults with MDS who underwent allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen. We detected mutations before transplantation using enhanced exome sequencing, and we evaluated mutation clearance by using error-corrected sequencing to genotype mutations in bone marrow samples obtained 30 days after transplantation. In this exploratory study, we evaluated the association of a mutation detected after transplantation with disease progression and survival.

RESULTS: Sequencing identified at least one validated somatic mutation before transplantation in 86 of 90 patients (96%); 32 of these patients (37%) had at least one mutation with a maximum variant allele frequency of at least 0.5% (equivalent to 1 heterozygous mutant cell in 100 cells) 30 days after transplantation. Patients with disease progression had mutations with a higher maximum variant allele frequency at 30 days than those who did not (median maximum variant allele frequency, 0.9% vs. 0%; P<0.001). The presence of at least one mutation with a variant allele frequency of at least 0.5% at day 30 was associated with a higher risk of progression (53.1% vs. 13.0%; conditioning regimen-adjusted hazard ratio, 3.86; 95% confidence interval [CI], 1.96 to 7.62; P<0.001) and a lower 1-year rate of progression-free survival than the absence of such a mutation (31.3% vs. 59.3%; conditioning regimen-adjusted hazard ratio for progression or death, 2.22; 95% CI, 1.32 to 3.73; P=0.005). The rate of progression-free survival was lower among patients who had received a reduced-intensity conditioning regimen and had at least one persistent mutation with a variant allele frequency of at least 0.5% at day 30 than among patients with other combinations of conditioning regimen and mutation status (P≤0.001). Multivariate analysis confirmed that patients who had a mutation with a variant allele frequency of at least 0.5% detected at day 30 had a higher risk of progression (hazard ratio, 4.48; 95% CI, 2.21 to 9.08; P<0.001) and a lower 1-year rate of progression-free survival than those who did not (hazard ratio for progression or death, 2.39; 95% CI, 1.40 to 4.09; P=0.002).

CONCLUSIONS: The risk of disease progression was higher among patients with MDS in whom persistent disease-associated mutations were detected in the bone marrow 30 days after transplantation than among those in whom these mutations were not detected. (Funded by the Leukemia and Lymphoma Society and others.).

[memo]
■知らない

Clearance :除去

Myelodysplastic :骨髄異形成

allogeneic :同種異型の

hematopoietic :造血の

predictor :予測因子

progression :腫瘍が大きくなること

myeloablative :骨髄破壊的な

reduced-intensity conditioning :強度軽減移植前療法

regimen :摂取法

exploratory :診査の

evaluate :評価する

association :関連、合同、協会

validated :確認する、有効にする、の過去形

somatic mutation :体細胞突然変異

Sequencing :DNAのヌクレオチド配列決定

variant :異なる

variant allele :変異型アレル

persistent :持続的な、頑固な

■使いたい

we evaluated mutation clearance by using

equivalent to

was associated with

The risk of disease progression was higher among

those in whom these mutations were not detecte

are unclear