First-line matched related donor hematopoietic stem cell transplantation compared to immunosuppressive therapy in acquired severe aplastic anemia

Abstract

Introduction: Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials.

Methods: A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival.

Results: 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies.

Conclusions: Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies.

Figure 1. Literature search and study flow.

Abbreviations: HSCT: hematopoietic stem cell transplantation; IST: immunosuppressive therapy; SAA: severe aplastic anemia.

Figure 2. Meta-analysis of all studies with available data.

Meta-analysis of overall survival using hazard-ratio as effect measure after first-line HSCT vs. first-line IST. Pooled estimate not justified because of considerable heterogeneity and of not sufficient external validity. Abbreviations: HSCT: hematopoietic stem cell transplantation; IST: immunosuppressive therapy; SAA: severe aplastic anemia; SE: standard error.

Figure 3. Funnel plot using data from Figure 3 .

Distribution of estimates can be regarded as funnel-shaped and compatible with a moderate publication bias. Abbreviations: SE: standard error.