Trasplante de progenitores hematopoyéticos con acondicionamiento de intensidad reducida: Aplicabilidad en leucemia mieloide aguda y síndromes mielodisplásicos.

Abstract

Allogeneic stem cell transplantation (Alo-SCT) is the only curative option for most patients_x000D_ diagnosed of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and in_x000D_ some other neoplastic and non-neoplastic hematological disorders. Nevertheless its_x000D_ applicability is reduced because of the high toxicity associated with the use of high dose_x000D_ chemo-radiotherapy used in the conditioning._x000D_ The development of conditioning regimens with lower toxicity, known as reduced intensity_x000D_ conditionings allow to offer the transplant procedure to those patients previously_x000D_ considered non-candidates because of high risk of toxicity with conventional transplant_x000D_ based on the use of high dose conditioning._x000D_ This doctoral thesis shows the result of three consecutive studies performed to analyze the_x000D_ feasibility and efficacy of a reduced intensity conditioning regimen in patients with AML and_x000D_ MDS._x000D_ The first study demonstrates that the reduced intensity conditioning regimen is associated_x000D_ with lower than expected non-relapse mortality. The second study presents the long term_x000D_ results and analyzes the factors associated with better results, showing that the_x000D_ development of chronic graft versus host disease is associated with improved survival._x000D_ The last study is a comparison between reduced intensity conditioning and other strategy_x000D_ aimed to reduce transplant related mortality as the transplant of CD34 positive cells_x000D_ selection graft that shows that reduced intensity conditioning show similar results, and_x000D_ possibly better in older patients._x000D_ As conclusions, the present doctoral thesis demonstrates: 1) The reduced intensity_x000D_ conditioning scheme used was able to achieve stable long term engraftment, 2) it is_x000D_ associated with lower transplant related mortality compared with conventional conditioning_x000D_ 3)obtaining the highest benefit in term of survival in patients developing chronic graft_x000D_ versus host disease and 4) with a global results similar to those obtained in younger_x000D_ patients using conventional conditioning regimens and CD 34 positive selected grafts. It_x000D_ ultimately confirms that reduced intensity conditioning regimen offers a curative option to_x000D_ those patients with risk of mortality with conventional approach and identifies the graft_x000D_ versus tumor effect as the main mechanism of action of this approach.

Date of Award	9 Apr 2014
Original language	Spanish
Supervisor	Jorge Sierra Gil (Director) & Rodrigo Martino Bofarull (Director)