Predictors of clonal evolution and myeloid neoplasia following immunosuppressive therapy in severe aplastic anemia View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-07-27

AUTHORS

Emma M. Groarke, Bhavisha A. Patel, Ruba Shalhoub, Fernanda Gutierrez-Rodrigues, Parth Desai, Harshraj Leuva, Yoshitaka Zaimoku, Casey Paton, Nina Spitofsky, Jennifer Lotter, Olga Rios, Richard W. Childs, David J. Young, Alina Dulau-Florea, Cynthia E. Dunbar, Katherine R. Calvo, Colin O. Wu, Neal S. Young

ABSTRACT

Predictors, genetic characteristics, and long-term outcomes of patients with SAA who clonally evolved after immunosuppressive therapy (IST) were assessed. SAA patients were treated with IST from 1989-2020. Clonal evolution was categorized as “high-risk” (overt myeloid neoplasm [meeting WHO criteria for dysplasia, MPN or acute leukemia] or isolated chromosome-7 abnormality/complex karyotype without dysplasia or overt myeloid neoplasia) or “low-risk” (non-7 or non-complex chromosome abnormalities without morphological evidence of dysplasia or myeloid neoplasia). Univariate and multivariate analysis using Fine-Gray competing risk regression model determined predictors. Long-term outcomes included relapse, overall survival (OS) and hematopoietic stem cell transplant (HSCT). Somatic mutations in myeloid cancer genes were assessed in evolvers and in 407 patients 6 months after IST. Of 663 SAA patients, 95 developed clonal evolution. Pre-treatment age >48 years and ANC > 0.87 × 109/L were strong predictors of high-risk evolution. OS was 37% in high-risk clonal evolution by 5 years compared to 94% in low-risk. High-risk patients who underwent HSCT had improved OS. Eltrombopag did not increase high-risk evolution. Splicing factors and RUNX1 somatic variants were detected exclusively at high-risk evolution; DNMT3A, BCOR/L1 and ASXL1 were present in both. RUNX1, splicing factors and ASXL1 somatic mutations detected at 6 months after IST predicted high-risk evolution. More... »

PAGES

2328-2337

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41375-022-01636-8

DOI

http://dx.doi.org/10.1038/s41375-022-01636-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149786269

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35896822


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20 Evolver
21 Fine-Gray
22 L1
23 RUNX1
24 SAA
25 SAA patients
26 age
27 analysis
28 anemia
29 aplastic anemia
30 cancer genes
31 cell transplant
32 characteristics
33 clonal evolution
34 eltrombopag
35 evolution
36 factors
37 genes
38 genetic characteristics
39 hematopoietic stem cell transplant
40 high-risk clonal evolution
41 high-risk patients
42 immunosuppressive therapy
43 long-term outcomes
44 model
45 months
46 mutations
47 myeloid neoplasia
48 neoplasia
49 outcomes
50 overall survival
51 patients
52 patients 6 months
53 pre-treatment age
54 predictors
55 regression models
56 relapse
57 risk regression models
58 severe aplastic anemia
59 somatic mutations
60 somatic variants
61 splicing factors
62 stem cell transplant
63 strongest predictor
64 survival
65 therapy
66 transplant
67 variants
68 years
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