Research lines

The implementation of new clinical trials takes years due to administrative regulations. In order not to lose relevant clinical and biological data about the patients diagnosed between clinical trials, and to allow further research projects, the NHL-SEHOP 2018 Registry was established all SEHOP centers. This project represents the main source of our research activity.

The NHL-SEHOP Group cooperates with the European Inter-Group for Childhood Non-Hodgkin Lymphoma (EICNHL) developing and conducting comprehensive clinical research programs, as international, multicenter trials for children and adolescents with NHL, and developing clinical guidelines and recommendations in rare pediatric NHL entities. For this purpose, the Group is involved in the implementation of new methodologies driven to improve a centralized diagnose, risk stratification and relapse surveillance of different NHL entities.

The implementation of clinical trials is supported by the SEHOP Foundation

International clinical trials contribution

Intergroup Trial for Children or Adolescents With B-Cell Non-Hodgkin Lymphoma or B-Acute Leukemia

Evaluation of Rituximab Efficacy and Safety in High-Risk Patients. Phase II/III Trial. EudraCT N°: 2010-019224-31.

LBL 2018

International Cooperative Treatment Protocol for Children and Adolescents with Lymphoblastic Lymphoma. Phase III. EudraCT N°: 2017-001691-39

Currently, the NHL-SEHOP Group is contributing in the design and implementation of new international clinical research projects.

Basic and translational research

Integrative genetic profile and identification of diagnostic markers

In order to achieve the complete global genetic landscape of NHL we are studying the molecular profile of poorly characterized non-Hodgkin lymphoma subtypes by high resolution techniques. Moreover, in order to go deep into the biology of these tumors and to identify age or refractoriness related markers, we are molecularly analyzing large retrospective series of pediatric and young adult NHL subtypes, including both in immunocompetent patients and in patients with primary and secondary immunodeficiencies in the frame of the Spanish Society of Pediatric Hematology and Oncology.

Study of intratumoral heterogeneity

Data already obtained in the analysis of pediatric NHL shows the presence of intratumoral heterogeneity that may represent the existence of different subclones. Although there are studies of the mutational hierarchy in adult NHL series, there is no approach in pediatric tumors. We aim to establish the mutational hierarchy in pediatric lymphoma types and determine the relationship between the presence of these mutations and histological areas corresponding to different morphological compartments by implementing different analysis pipelines and establishing in situ mutational detection probes. Also, we attempt, after generation of the necessary cryopreserved tissue collection, to set up in the lab single-cell techniques that could be applied to pediatric NHL tissue samples.

Identification of genetic biomarkers and drug targets

Our final goal is to identify target genes/pathways that can be useful biomarkers in the management of pediatric NHL. In detail, we aim to identify markers that can contribute to the design of more adapted therapies, improve the stratification of patients according to risk (markers associated with relapse/refractoriness) or markers whose presence/absence identify patients who do not need treatment or may be possible to de-escalate the chemotherapy doses of current protocols. Moreover, function of specific deregulated genes can be modified using drugs, opening the door to more effective therapies.

Liquid biopsy

Although tissue biopsy is the gold standard for adequate characterization of primary tumors, recent studies in adult NHL have shown that analysis of circulating lymphoma nucleic acids in liquid biopsies is a minimally invasive method that provides adequate material for the study of tumor genetic alterations. Unfortunately, there are scarce studies in the pediatric population. Liquid biopsy can offer an integrated view of the tumor and can help in the identification of mutations driving progression or relapse with therapeutic implications. This technic might be especially useful in cases in which obtaining a surgical biopsy is difficult or even represents a risk for the patient (eg., in primary lymphomas of the central nervous system).