Allogeneic Hematopoietic Cell Transplantation Is an Effective Treatment for Patients with Richter Syndrome: A Systematic Review and Meta-Analysis.

Background Richter syndrome (RS) represents an aggressive disease resulting from transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell or Hodgkin lymphoma. In 80% of cases, RS is clonally related to CLL. New therapies like ibrutinib have limited efficacy in RS with anticipated median overall survival (OS) of 3.5 months from the time of CLL transformation. Adriamycin-based regimens combined with rituximab represent the standard induction treatment for RS; and those who demonstrate responsive disease are generally offered an allogeneic hematopoietic cell transplant (allo-HCT) despite the lack of randomized controlled studies. Outcomes following allo-HCT in RS are limited to single-institution case series or registry data. We performed a systematic review of the medical literature to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in RS. Material and methods We performed a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 28, 2018. We extracted data on clinical outcomes pertaining to the benefits (complete remission [CR], OS and progression-free survival [PFS]) and harms (relapse and non-relapse mortality [NRM]), independently by two authors. Our search identified a total of 240 references. Four studies (n= 72 patients) were eligible for inclusion in this systematic review/meta-analysis (Figure 1). Three single-institution studies were from the United States and one data registry study from the European Society for Blood and Marrow Transplantation. Results Reduced intensity conditioning (RIC) regimens were more commonly prescribed (n=50, 69.4%) and the cell source was predominantly peripheral blood stem cells (n=54, 75%). Post-allograft pooled CR rate (3 studies, n=47 patients) was 33% (95%CI=4-71%) with high heterogeneity among studies (I2 =84.2%). Pooled OS rate (3 studies, n=52 patients) was 54% (95%CI=28-79%) with high heterogeneity among studies (I2 =69.8%) (Figure 2) ; and these 3 studies reported OS at 4-years, 3-years and 2-years, respectively. Pooled PFS (3 studies, n=52 patients) was 30% (95%CI=18-44%) with no heterogeneity among studies (I2 =0). Pooled relapse rates (3 studies, n=52 patients) was 28% (95%CI=9-52%) with high heterogeneity (I2 =62.7%). Pooled NRM associated with allo-HCT was 24% (95%CI=29.4%) with low heterogeneity (I2 =29.4%). Conclusion Allo-HCT is an effective treatment for RS with a resulting pooled OS rate (between 2-4 years) of 54%. One study identified age (< 60 years), chemosensitive disease and use of RIC regimens to be associated with better relapse-free survival. Feasibility and efficacy of combining novel therapies +/- donor lymphocyte infusion(s) should be studied to help reduce the risk of post-transplant relapse. [ABSTRACT FROM AUTHOR]