Outcomes of Hematopoietic Stem Cell Transplantation in Primary Plasma Cell Leukemia: A Systematic Review and Meta-Analysis

Background: Hematopoietic cell transplantation is a pivotal treatment modality for primary plasma cell leukemia (pPCL). Historically, pPCL has a poor prognosis and given its rarity, randomized controlled trials to explore treatment modalities are limited. In this systematic review and meta-analysis, we aimed to examine the outcomes of Allogeneic (Allo-SCT) and Autologous stem cells (Auto-SCT) transplantation in the adult pPCL population.

Methods: Following the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) guidelines, a comprehensive literature search was performed on PubMed, Cochrane Register of Controlled Trials, Embase, and Clinicaltrials.gov using MeSH terms and keywords for “Plasma cell leukemia” “Hematopoietic Stem Cell Transplantation” AND “therapeutics” from the date of inception till June 31, 2024. Our search produced 603 articles. After excluding irrelevant and review articles during primary and secondary screening, twelve original studies reporting outcomes of Allo-SCT and/or Auto-SCT in pPCL were included. The inter-study variance was calculated using the Der Simonian-Laird Estimator proportions and a 95% Confidence Interval (CI) was extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.3.0).

Results: A total of 1757 pPCL patients aged 18 years or older with auto-SCT or Allo-SCT were included in the analysis, and 49% of the participants were males (n=861/1757). The auto-SCT cohort comprised 1535 patients from 11 studies, with a median age of 57.35 (25-85) years, while the Allo-HCT group included 222 patients from six studies, with a median age of 49.5 (20-68) years. The median follow-up time was 4.03 (0.2-12.4) years in the auto-SCT and 3.35 years (0.25-7.6) in the Allo-SCT group. The median time to transplant was 0.53 (0.16-7.8) years and 0.55 (0.16-4.8) years in auto-HCT and Allo-HCT groups, respectively. The pooled 3 years overall survival (OS), progression-free survival/Event-free survival (PFS/EFS), and relapse rate (RR) in Auto-SCT were 51% (95% CI 0.4-0.61, I²=92%, p=<0.01), 36% (95% CI 0.24-0.52, I 2 =97%, p<0.01), and 68% (95% CI, 0.65-0.71, I2=0%, p=0.42), respectively. Among Allo-SCT recipients, the reported OS varied from 71% at 2.3 years (Landsburg et al.) to 31% at 4 years (Dhakal et al.), and EFS/PFS from 29% at 2.5 years (Royer et al.) to 19% at 4 years (Dhakal et al.). The pooled treatment-related mortality (TRM) was 12 % (95 % CI 0.05-0.25, I ²=35 %, p=0.22) at a median of 6 months. The pooled acute and chronic graft versus host disease (aGvHD and cGVHD) incidences were 27% (0.19-0.36, I2= 30%, p= 0.21) and 36% (0.27-0.45, I2= 24%, p= 0.26), respectively.

Conclusion: Our systematic review and meta-analysis show stem cell transplantation remains the backbone of primary plasma cell leukemia treatment. However, higher relapse rates warrant novel agents and clinical trials to improve transplant-related outcomes in this challenging subgroup.