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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

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Abstract

Somatic 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.

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Acknowledgments

Spanish Group of Myelodysplastic Syndromes (GESMD)

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work has been supported by Gerencia Regional de Salud de Castilla y León (GRS 1033/A/14), Instituto de Salud Carlos III - Fondo de investigación sanitaria (FIS PI17/01741), Instituto de Salud Carlos III - Contratos Río Hortega (CM17/0017), Instituto de Salud Carlos III & FEDER funds (PI16/01302), and CIBERONC Centro de Investigación Biomédica en Red Cáncer (CB16/12/00284).

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Author notes

  1. Juan Carlos Caballero and Mercedes Sánchez Barba contributed equally to this work.

Authors and Affiliations

  1. Hematology Department, University Hospital of Salamanca, IBSAL Institute for Biomedical Research of Salamanca, Paseo de San Vicente, 139, 37007, Salamanca, Spain

    Juan Carlos Caballero, Mónica Cabrero, Félix López Cadenas, Jesús María Hernández Rivas, María Consuelo del Cañizo & María Díez Campelo

  2. Department of Statistics, Faculty of Medicine, University of Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain

    Mercedes Sánchez Barba

  3. IBMCC Institute of Cancer Molecular and Cellular Biology, CIC Cancer Research Institute (USAL-CSIC), IBSAL Institute for Biomedical Research of Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain

    Jesús María Hernández Sánchez, Kamila Janusz, Eva Lumbreras, María Abáigar & Jesús María Hernández Rivas

  4. Hematology Department, University and Polytechnic Hospital La Fe, Av. de Fernando Abril Martorell, 106, 46026, Valencia, Spain

    Esperanza Such, Guillermo Sanz & José Cervera

  5. Molecular Biology Department, University Hospital of Salamanca, Paseo de San Vicente, 139, 37007, Salamanca, Spain

    Carmen Chillón

  6. Hematology and Clinical Oncology Department, University Hospital Morales Meseguer, Av. Marqués de los Vélez, 30008, Murcia, Spain

    Ana María Hurtado & Andrés Jerez

  7. Hematology Department, University Hospital Virgen del Rocío, Av. Manuel Siurot, 41013, Sevilla, Spain

    Cristina Calderón Cabrera

  8. Hematology Department, University Hospital Vall d’Hebron, Passeig de la Vall d’Hebron, 119-129, 08035, Barcelona, Spain

    David Valcárcel

  9. Area of Genetic and Cellular Therapy, IBSAL Institute for Biomedical Research of Salamanca, Paseo de San Vicente 58-182, 37007, Salamanca, Spain

    María Consuelo del Cañizo & María Díez Campelo

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  1. Juan Carlos Caballero
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Correspondence to María Díez Campelo.

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This research has been performed in accordance with the Declaration of Helsinki and has been approved by the ethics committee of the University Hospital of Salamanca, which has assigned the reference number 2014/07/110.

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Caballero, J.C., Sánchez Barba, M., Hernández Sánchez, J.M. et al. Chronic graft-versus-host disease could ameliorate the impact of adverse somatic mutations in patients with myelodysplastic syndromes and hematopoietic stem cell transplantation. Ann Hematol 98, 2151–2162 (2019). https://doi.org/10.1007/s00277-019-03751-6

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