Feasibility of allogeneic hematopoietic stem cell transplantation in advanced age.

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.

A Different View for an Old Disease: NEDDylation and Other Ubiquitin-Like Post-Translational Modifications in Chronic Lymphocytic Leukemia.

Despite the enormous amount of molecular data obtained over the years, the molecular etiology of chronic lymphocytic leukemia (CLL) is still largely unknown. All that information has enabled the development of new therapeutic approaches that have improved life expectancy of the patients but are still not curative. We must increase our knowledge of the molecular alterations responsible for the characteristics common to all CLL patients. One of such characteristics is the poor correlation between mRNA and protein expression, that suggests a role of post-translational mechanisms in CLL physiopathology. Drugs targeting these processes have indeed demonstrated an effect either alone or in combination with other aimed at specific pathways. A recent article unveiled an increment in ubiquitin-like modifications in CLL, with many protein members of relevant pathways affected. Interestingly, the inhibition of the NEDD8-activating protein NAE reverted a substantial number of those modifications. The present review gets the scarce data published about the role of NEDDylation in CLL together and establishes connections to what is known from other neoplasias, thus providing a new perspective to the underlying mechanisms in CLL.