Research

Area 5

Hematopoietic progenitor cell transplantation

Team leader

Strategic objectives

In the last few years our group has developed basic and translational research lines, thanks to the collaboration with other research groups of the Clinic Hospital (Department of Immunology, Department of Hemostasis) and of the Medical School (Department of Human Anatomy).

Very recently, we have established research space of our own in the CEK, and at the School of Medicine (Institute of Research Josep Carreras), and have expanded our collaboration with other research groups – particularly in reference to cell therapy. Likewise, we have started the expansion of hematopoietic precursors from umbilical cord blood based on co-cultures of mesenchymal cells and research lines in antitumor cell therapy, anti-infectious treatment and cell immune modulation. Functional studies of genetic polymorphisms have also been consolidated. Lastly, we plan to develop a line of research in the field of the pharmacokinetics, pharmacodynamics and pharmacogenomics of immune modulators, as well as in the development of in vitro predictive models of graft-versushost disease.

Main lines of research

Clinical research lines

  1. Assessment of new hematopoietic precursor transplantation (HPT) indications. Treatment of diseases such as amyloidosis, POEMS syndrome, scleromyxedema, autoimmune disorders (multiple sclerosis, Crohn’s disease, lupus erythematosus), primary myelofibrosis or paroxysmal nocturnal hemoglobinuria – these being diseases in which our group has the most extensive experience in the country.
  2. Evaluation of new progenitor sources (high-complexity hematopoietic precursor transplantation). The lack of compatible siblings for all patients amenable to hematopoietic precursor transplantation is leading to the development of transplants from nonconsanguineous donors or umbilical cord blood. We are the most active group in the country in relation to these high complexity procedures, which represent 30% of our activity.
  3. Evaluation of new transplant modalities.
    • Domiciliary autogenicHPT (unique in Europe, awarded on several occasions by the scientific and healthcare societies) – a modality which we aim to extend to domiciliary allogenic HPT.
    • Haploidentical transplantation with unmanipulated bone marrow.
  4. Studies addressing the prevention and treatment of the main complications of HPT.
    • Prevention and treatment of graftversus-host disease with new agents (anti-IL-2 receptor antibodies, new antithymocyte globulins, alemtuzumab and cell therapy using mesenchymal cells Participation in different multicenter0 studies.

Basic and translational research lines

  1. Study of the post-HPT complications originating from endothelial dysfunction. Different early complications appearing after HPT, such as veno-occlusive syndrome, capillary rupture syndrome, thrombotic microangiopathy, graft syndrome, and idiopathic pneumonia syndrome, appear to originate from endothelial dysfunction. Our project aims to characterize such dysfunction and the early diagnosis of infections then to seek effective preventive in HPT. Following the advances and treatment options. This research made in the early diagnosis of line is supported by two FIS grants fungal diseases (galactomannan and an aid from the German José antigen, high-resolution CAT) and Carreras Foundation.
  2. Study of immune reconstitution following HPT. Following characterization of immune reconstitution in HPT from bone marrow, peripheral blood and in reduced intensity regimens, we plan to assess immune reconstitution in the transplantation of umbilical cord blood – this not ever having been achieved to date.
  3. Study of the impact of genic polymorphisms upon the complications and outcomes of HPT. Following demonstration of the impact of the mannose-binding lectin variants upon the incidence of fungal infections, of the NOD2/CARD15 gene variants upon survival and the incidence of bronchiolitis obliterans and, more recently, of the impact of the NLRP2 and NLRP3 gene variants upon HPT survival, we plan to continue this line of research, assessing new polymorphisms that may affect the evolution of HPT.
  4. Study of new techniques for the early diagnosis of infections in HPT. Following the advances made in the early diagnosis of fungal diseases (galactomannan antigen, high-resolution CAT) and viral infections (CMV antigenemia and PCR applied to all herpes viruses and other pathogens), which have facilitated our healthcare activities, we plan to continue evaluating new diagnostic techniques (quantitative PCR for EBV, the application of PCR to tissue samples, biological markers in bronchoalveolar lavage, and PET scan assessment of infections).
  5. Development of CARTs using NK cells expanded from umbilical cord blood