Current concepts in the pathophysiology and treatment of aplastic anemia

Abstract

Historically viewed in isolation as an odd, rare, and invariably fatal blood disease, aplastic anemia is now of substantial interest for its immune pathophysiology, its relationship to constitutional BM failure syndromes and leukemia, and the success of both stem cell transplantation and immunosuppressive therapies in dramatically improving survival of patients. Once relegated to a few presentations in the red cell and anemia sessions of the ASH, the Society now sponsors multiple simultaneous sessions and plenary and scientific committee presentations on these topics. This update emphasizes developments in our understanding of immune mechanisms and hematopoietic stem cell biology and new clinical approaches to stem cell stimulation as a therapy, alone and in combination with conventional suppression of the aberrant immune system.

Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis

“…with prompt and correct management, AA is now curable in a high proportion of cases [2]. The pathophysiology of acquired AA is based, generally, on the immune destruction of hematopoietic progenitors [2].…”

Matched Sibling Versus Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation in Children with Severe Acquired Aplastic Anemia: Experience of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation

“…In the cohorts studied, the risk of graft failure after MUD-HSCT was higher than after MSD-HSCT, but it was comparable to the results reported by the majority of other authors (Bacigalupo et al 2000(Bacigalupo et al , 2005(Bacigalupo et al , 2010Kosaka et al 2008;Passweg et al 2006;Storb et al 2001;Viollier et al 2008) despite giving lower total dose of thymoglobulin (10 vs. 15 mg/kg). The higher risk of non-engraftment in children transplanted from MUD could be related to a higher number of unavoidable pre-transplant transfusions in children who had been first treated ineffectively with IST and then, after 6-12 months, qualified for MUD-HSCT (Kumar et al 2006;Srinivasan et al 2006;Young et al 2006). In the context of graft failure, it is worth mentioning that the second transplantation is feasible and may offer rescue to these patients.…”

“…Thus, it is comparable to OS rates in children transplanted during the last decade, as reported by the majority of authors (Locasciulli et al 2007; http://www. cibmtr.org), and is still significantly less favorable in children who underwent MUD-HSCT (Kojima et al 2002;Young et al 2006). Nowadays, however, the probability of OS in the patients undergoing MUD-HSCT is significantly better than it was in the 1990s, i.e., before the implementation of high-resolution HLA typing (Deeg et al 1999;Maury et al 2009;Young et al 2006).…”

“…cibmtr.org), and is still significantly less favorable in children who underwent MUD-HSCT (Kojima et al 2002;Young et al 2006). Nowadays, however, the probability of OS in the patients undergoing MUD-HSCT is significantly better than it was in the 1990s, i.e., before the implementation of high-resolution HLA typing (Deeg et al 1999;Maury et al 2009;Young et al 2006). Recently, Bacigalupo et al (2005Bacigalupo et al ( , 2010 demonstrated that in SAA patients undergoing HSCT from alternative donors further improvement of 2-year OS is possible up to 73 %, with a trend for even better outcome in patients aged B14 years (84 %), when using conditioning regimen consisting of FLUDA, low-dose cyclophosphamide, and anti-thymocyte globulin (the FCA regimen).…”

“…So far the following factors have been recognized as predictors of better survival rates after allogeneic HSCT in patients with SAA: younger age (\16 years) (Locasciulli et al 2007), short interval between diagnosis and HSCT (Locasciulli et al 2007), minimum of blood products transfusion (Srinivasan et al 2006;Young et al 2006), no radiation in the conditioning regimen (Locasciulli et al 2007), HLA-matching at the allelic level (Deeg et al 2006;Maury et al 2007), transplantation after 1996 (Locasciulli et al 2007), MSD-HSCT (Locasciulli et al 2007), and BM from MSD as stem cells source (Schrezenmeier et al 2007). In our study, both in univariate and in multivariate analysis, the type of matched donor was identified as the only one independent factor significantly related to the probability of survival, with better prognosis in patients transplanted from MSD, but we had no appropriate data to evaluate the impact of time from diagnosis to transplantation.…”