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This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant., Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Depto. de Medicina, Fac. de Medicina, TRUE, pub

El trasplante alogénico de progenitores hematopoyéticos (Alo-TPH), descubierto en los años 50, constituye en la actualidad una herramienta terapéutica para el manejo de enfermedades hematológicas. Con altas tasas de morbi-mortalidad, la enfermedad injerto contra receptor (EICR) es su complicación más importante. El análisis del quimerismo hematopoyético, es decir del porcentaje de celularidad del donante o del receptor tras la infusión del injerto, es utilizado clínicamente para el seguimiento post Alo-TPH, siendo utilizado para predecir diversas complicaciones, más aún cuando éste se lleva a cabo sobre linajes leucocitarios. En este contexto, y conocido el papel de los linfocitos T (CD3+, LT), los leucocitos activados (CD25+, LA) y linfocitos T reguladores (CD4+/CD25+, Tregs) en el Alo-TPH, el objetivo de este estudio es el análisis del quimerismo en dichos linajes y su implicación en el desarrollo de complicaciones. El análisis del quimerismo hematopoyético se llevó a a cabo mediante PCR de microsatélites sobre muestras de ADN de SP, y linajes leucocitarios (LT, LA y Tregs) purificados mediante técnicas inmunomagnéticas, con posterior electroforesis capilar. La dinámica del quimerismo hematopoyético así como la consecución de QC en LA y Tregs mostró diferencias con respecto a la observada en SP y LT, con una consecución de QC más tardío y un mayor porcentaje de celularidad de receptor en los primeros 100 días tras el Alo-TPH. La consecución de QC en LA predice mejor el desarrollo de EICR aguda que el QC en LT. Sin embargo, ni la dinámica de quimerismo ni el QC afectó a la SG, SLE ni a la MRT. En cuanto a los Tregs, la dinámica de quierismo y el QC no afectaron al desarrollo de EICR. Aunque tampoco afectaron a la SG o la SLE, existe una tendencia a una menor MRT y mejores resultados cuando los pacientes adquieren QC de manera tardía..., Allogeneic stem cell trasnplantation (Allo-SCT) is a procedure discovered around 1950, and is currently worldwide used as a regular therapeutic tool for the treatment of malignant and non-malignant hematological diseases. Its success resides in the substitution of the lymphohematopoietic system of a patient, from a healthy one from a different person. Despite the better knowledge of the immunobiology of Allo-SCT, and a better management of its complications, it is still a procedure with high rates of morbidity and mortality, with long term survival rates around 40-50%, and a transplant related mortality around 20%. Graft versus host disease (GVHD, acute or chronic) is the main cause of morbidity-mortality. Donor cells, once infused in the patient and after an activation process, recognize recipient́s cellularity and attack it mainly in gut, skin and liver. However, this complication is associated with the known graft versus leukemia effect, in which donor cellularity erradicate residual tumor cells in the patient. This allotolerance and alloreactivity balance between donor and recipient plays an important role in the transplant outcome, with different methods described to analyze it. Chimerism analisys is one of them, that studies the balance between donor and recipient hematopoietic cellularity after infusion, and in which complete chimerism (100% donor cells) is associated with better outcome but higher degree of GVHD, and mixed chimerism (<100% donor cells) is associated with lower complications but higher rates of disease relapse. The role of CD25+ activated leukocytes (LA) and CD4+/CD25+ T regulatory cells (Tregs) has been studied in the Allo-SCT setting, and their association with the development of several comlicactions after it. Though, the main objective of this study is to analyse the chimerism dynamic of LA y Tregs in the after Allo-SCT and its role in the development of the main complications after transplant...