Efficacy of Autologous and Allogeneic Hematopoietic Cell Transplantation in Waldenström Macroglobulinemia: A Systematic Review and Meta-analysis

Abstract

We performed a systematic review and meta-analysis of all the available data to assess the efficacy of autologous (AHCT) and allogeneic (allo-HCT) hematopoietic cell transplantation for Waldenström macroglobulinemia. Both AHCT and allo-HCT are efficacious, resulting in complete response rates of around 20% with allo-HCT affording a 2-fold lower relapse rate, which is offset by a 7-fold higher non-relapse mortality compared with AHCT. Introduction: Waldenström macroglobulinemia (WM) is an IgM-producing lymphoproliferative disorder that remains incurable. Patients with high-risk disease have an overall survival (OS) of less than 3 years. Both autologous (AHCT) and allogeneic (allo-HCT) hematopoietic cell transplantation (HCT) are prescribed for treatment of WM despite a lack of randomized controlled studies. Materials and Methods: We performed a comprehensive literature search using PubMed/Medline and EMBASE on September 10, 2019. Data on clinical outcomes related to benefits and harms was extracted independently by 3 authors. Fifteen studies (8 AHCT [n ¼ 278 patients], 7 allo-HCT [n ¼ 311 patients]) were included in this systematic review/meta-analysis. Results: Pooled OS, progression-free survival (PFS), and nonrelapse mortality (NRM) rates post AHCT were 76% (95% confidence interval [CI], 65%-86%), 55% (95% CI, 42%-68%), and 4% (95% CI, 1%-7%), respectively. Pooled OS, PFS, and NRM rates post allografting were 57% (95% CI, 50%-65%), 49% (95% CI, 42%-56%), and 29% (95% CI, 23%-34%), respectively. OS and PFS rates were reported at 3 to 5 years, and NRM was reported at 1 year in most studies. Pooled ORR (at day 100) post AHCT and allo-HCT were 85% (95% CI, 72%-94%) and 81% (95% CI, 69%-91%), respectively. Pooled complete response rates post AHCT and allo-HCT were 22% (95% CI, 17%-28%) and 26% (95% CI, 7%-50%), respectively. Relapse rates post AHCT and allo-HCT were 42% (95% CI, 30%-55%) and 23% (95% CI, 18%-28%), respectively. Conclusions: Our results show that both AHCT and allo-HCT are effective in the treatment of WM. A 2-fold lower relapse rate but a 7-fold higher NRM was noted for allo-HCT compared with AHCT. The role of transplant in WM needs to be addressed in the era of novel agents.

Systematic reviews in hematopoietic cell transplantation and cellular therapy: considerations and guidance from the American Society for Transplantation and Cellular Therapy, European Society for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research late effects and quality of life working committee

“…Several tools are available for evaluating the risk of bias within a study and across studies. The Cochrane risk-of-bias tool may be used for RCTs [58,59], ROBINS-I for nonrandomized studies of interventions [60], and the Newcastle-Ottawa Scale for observational studies [61][62][63]. Case reports and small case series cannot be assessed for risk of bias.…”

“…Including only randomized or quasi-randomized studies in a systematic review may be possible for a well-studied topic [71]. However, it still may be appropriate to perform a meta-analysis with few RCTs [59] and/or retrospective cohort studies if the quality of the studies is high [63]. However, pooling data from poor-quality studies into a meta-analysis is not recommended, because errors and biases from individual studies will be compounded, yielding misleading results and conclusions.…”

Successful Treatment of Factor X Deficiency in a Patient with Lymphoplasmacytic Lymphoma with Bendamustine Plus Rituximab Regimen: A Case Report and Literature Review

“…Autologous and allogeneic stem cell transplantation should be carefully considered due to the high rate of non-relapse mortality in lymphoplasmacytic lymphoma. 27 The benefits and drawbacks of this treatment alternative will be discussed with our patient so that a plan can be in place when and if our patient relapses.…”

Post‐relapse survival in Waldenstrom macroglobulinemia patients experiencing therapy failure following autologous transplantation

“…Congruently in our analysis, a higher number of previous lines of therapy is correlated to the risk of relapse, which is similar to other reports which describe that more than 3 lines of therapy impact PFS. 43 Current consensus guidelines agree that auto-HCT is an appropriate treatment option following second and subsequent relapses in high-risk patients with chemosensitive disease, however, it is not an appropriate treatment option in patients with WM responding and tolerating B cell receptor inhibitors. Furthermore, treatment decisions for transplant should preferentially be based on the clinical course (response and duration of response) rather than on biological/genetic factors (CXCR4, p53 molecular abnormalities, etc.)…”

“…12,13 While the role of auto-HCT in WM has been studied in registry databases, co-operative groups, and large single-center studies, data on treatment post-auto-HCT is extremely limited and mainly discussed in relation to allogeneic HCT (allo-HCT). 14,15 Hence, we sought to evaluate the long-term outcomes of WM patients who relapsed following auto-HCT and examined the factors prognostic of post-auto-HCT survival. All patients had disease with multiple relapses and we hypothesized that relapse after auto-HCT may have improved in the current era with the availability of novel agents.…”