Evaluation of effectiveness of hematopoietic stem cell transplantation for the treatment of patients with primary immunodeficiencies: a comprehensive systematic review and meta-analysis 1968-2017

Abstract

ABSTRACT: Background: Hematopoietic stem cell transplantation (HSCT) is the only available treatment with curative potential for patients with primary immunodeficiencies (PID). The effectiveness results measured in terms of overall survival (OS) and event-free survival (EFS) have improved markedly, however, there is a high heterogeneity in those results according to type of PID and when and where the transplant is performed. Despite its clinical importance in the decision-making process on whether to perform the transplant or not, a systematic evaluation of the effectiveness in these patients has never been made. Objectives: To evaluate the effectiveness of HSCT in patients with PID reported in the scientific literature and its relation with variables of type of disease, year of publication, region and age of the transplant. Methods: systematic review and meta-analysis with random effects model. In 9 databases, with 36 different search strategies. The exhaustivity and evaluation of the methodological quality was guaranteed. Studies were described with frequencies, the effectiveness meta-analyzed for OS and EFS in all studies, and specifically according to type of PID, continent, sex, donor compatibility and age of the transplant. Meta-regression was carried out to know the change in effectiveness over time. In the meta-analyzes heterogeneity was evaluated with I2 and Cochrane Q test and sensitivity with elimination of each article independently, the confidence was 95%. Results: A total of 135 articles with complete information on the effectiveness of HSCT in 5259 patients with PID were included; most patients were reported in Europe, North America, and Asia. The main justifications for the transplant were the presence of infections, phenotypic confirmation and genetic diagnosis. The most frequent complications were acute graft versus host disease (GVHD) and infections. The cumulative OS and EFS was 67% (CI 65-69) and 59% (CI 54-63%), respectively. Survival has increased 3% every year. Survival after the first years of transplantation seems to be stable. No differences were found in survival by sex or donor compatibility. Patients who survived the procedure were diagnosed and transplanted earlier and had to wait less time to receive the transplant after being diagnosed than the patients who died. Conclusion: HSCT is an increasingly effective procedure for the treatment of PID. The decision to perform the transplant should be made as soon as the phenotypic confirmation of the PID is taken, to avoid the risk of complications and increase the probability of survival.