Biomarcadores y complicaciones relacionadas con el trasplante haploidéntico de progenitores hematopoyéticos con ciclofosfamida postrasplante

Zusammenfassung

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for multiple hematological diseases. During the last years, the use of haploidentical donors for this purpose has increased exponentially worldwide, since it is a fast, cheap and effective alternative. In Spain and much of Europe, the most common graft-versus-host disease (GVHD) prophylaxis regimen used for this type of donor is the Baltimore protocol consisting of high doses of cyclophosphamide (Cy) post-transplant. Despite the optimization of its use, the incidence of non-relapse mortality (NRM) after transplantation is up to 30% at 2 years. The most common etiologies of NRM are infection followed by GVHD. In this context, in-depth knowledge of the features of haploidentical HSCT and its outcomes, as well as the development of biomarkers that help us detect high-risk patients is essential to improve the morbidity and mortality of the procedure. Thus, one of the most frequent complications after haploidentical allo-HSCT is cytokine release syndrome (CRS) that occurs after hematopoietic stem cell infusion, when alloreactive T lymphocytes of the donor interact with the recipient´s tissues. Its knowledge is essential to study its association with other post-transplant complications and optimize its clinical management. On the other hand, in recent years different plasma biomarkers with utility in prediction and diagnosis of GVHD and NRM have been described. Most of these studies have been performed in allo-HSCT with related and unrelated HLA identical donors. There are few studies in the haploidentical HSCT setting, therefore, research topic is of undoubted interest to the scientific community due to its novelty and practical applicability, since the Gregorio Marañón Hospital is a reference center for this transplant setting. Objectives: - Analyze CRS in patients undergoing haploidentical allo-HSCT with post-transplant Cy, indentify risk factors and their association with the development of posttransplant complications (Paper 1). - Quantify plasma levels of elafin, REG3α and ST2 at days +15 and +30 in patients undergoing haploidentical allo-HSCT with post-transplant Cy and their correlation with post-transplant complications (GVHD and NRM) (Papers 2 and 3). - Establish, for the biomarkers studied, a predictive cut-off point for some of the post-transplant complications (Papers 2 and 3).