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Chronic graft-versus-host disease could ameliorate the impact of adverse somatic mutations in patients with myelodysplastic syndromes and hematopoietic stem cell transplantation

AuthorsCaballero, Juan-Carlos; Sánchez Barba, Mercedes; Hernandez-Sánchez, Jesus M.; Such, Esperanza; Janusz, Kamila; Sanz, Guillermo; Cabrero, Mónica; Chillón, M. del Carmen; Cervera, José; Hurtado, Ana María; Jerez, Andrés; Calderón-Cabrera, Cristina; Valcárcel, David; Lumbreras, Eva CSIC ORCID; Abáigar, María CSIC; López Cadenas, Félix; Hernández, Jesús M. CSIC ORCID ; Cañizo, María Consuelo del; Díez-Campelo, María
KeywordsMyelodysplastic syndromes
Somatic mutations
Allogeneic hematopoietic stem cell transplantation
Chronic graft-versus-host disease
Issue Date2019
PublisherSpringer Nature
CitationAnnals of Hematology 98: 2151-2162 (2019)
AbstractSomatic mutations in patients with myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSTC) are associated with adverse outcome, but the role of chronic graft-versus-host disease (cGVHD) in this subset of patients remains unknown. We analyzed bone marrow samples from 115 patients with MDS collected prior to HSCT using next-generation sequencing. Seventy-one patients (61%) had at least one mutated gene. We found that patients with a higher number of mutated genes (more than 2) had a worse outcome (2 years overall survival [OS] 54.8% vs. 31.1%, p = 0.035). The only two significant variables in the multivariate analysis for OS were TET2 mutations (p = 0.046) and the development of cGVHD, considered as a time-dependent variable (p < 0.001), correlated with a worse and a better outcome, respectively. TP53 mutations also demonstrated impact on the cumulative incidence of relapse (CIR) (1 year CIR 47.1% vs. 9.8%, p = 0.006) and were related with complex karyotype (p = 0.003). cGVHD improved the outcome even among patients with more than 2 mutated genes (1-year OS 88.9% at 1 year vs. 31.3%, p = 0.02) and patients with TP53 mutations (1-year CIR 20% vs. 42.9%, p = 0.553). These results confirm that cGVHD could ameliorate the adverse impact of somatic mutations in patients with MDS with HSCT.
Publisher version (URL)http://dx.doi.org/10.1007/s00277-019-03751-6
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