CXCR4 Expression in Mantle Cell Lymphoma and Mobilization with Plerixafor for ASCT Does Not Negatively Impact Progression-Free Survival

Introduction: Mantle cell lymphoma (MCL) is a rare B-cell malignancy comprising 5-10% of all non-Hodgkin lymphoma cases.  Autologous hematopoietic stem cell transplant has emerged as a viable therapy for many patients with MCL.  An important step in the harvesting of peripheral blood hematopoietic stem cells (HSC) is mobilizing CD34⁺ HSC to the peripheral blood.  The novel compound plerixafor is an antagonist of CXCR4, and has been successful in mobilization of HSC for autologous stem cell transplants for non-Hodgkin lymphoma.  Increased mobilization of HSC in peripheral blood carries the risk of increased mobilization of lymphoma cells.  Since MCL expresses CXCR4, we sought to determine whether administration of plerixafor can adversely affect outcome in transplantation.  We report survival results of autologous peripheral blood stem cell transplants (ASCT) for patients with MCL who were treated with and without plerixafor for HSC mobilization prior to ASCT at Mayo Clinic.

Methods: The present study is a retrospective cohort study of all adult patients who underwent ASCT for treatment of MCL at Mayo Clinic from February 1993 to December 2013.  Patients were divided into two cohorts: (1) patients treated with plerixafor for HSC mobilization prior to ASCT, and (2) patients not treated with plerixafor prior to ASCT.  The primary outcome was relapse of MCL.  Overall survival from diagnosis and overall survival from transplant were also analyzed.

Patients: From 1993 to 2013, 169 consecutive patients underwent ASCT; 55 patients received plerixafor for HSC mobilization prior to ASCT, and 114 patients did not receive plerixafor.  The median ages at MCL diagnosis and ASCT for the plerixafor cohort were 57.7 years and 58.4 years, respectively, compared with 56.6 years and 58.1 years for the non-plerixafor cohort. 

Results: The average CD34⁺ HSC harvest with plerixafor was 5.4 × 10⁶/kg compared to 4.9 × 10⁶/kg without plerixafor (p = 0.13).  Median progression-free survival from ASCT was 3.4 years in the plerixafor cohort compared with 3.6 years in the non-plerixafor cohort (p = 0.69).  Median overall survival from ASCT was not reached in the plerixafor cohort compared with 5.7 years in the non-plerixafor cohort (p = 0.95).  Median overall survival from MCL diagnosis was 8.9 years in the plerixafor cohort compared with 7.6 years in the non-plerixafor cohort (p = 0.71).

Conclusions: ASCT for treatment of MCL performed at Mayo Clinic resulted in no statistically significant differences in progression-free and overall survival between patients receiving and patients not receiving plerixafor for CD34⁺ HSC mobilization prior to ASCT.  The results of this study indicate that HSC mobilization using plerixafor is not associated with decreased progression-free or overall survival from ASCT in MCL.  There appears to be no clinically significant mobilization of lymphoma cells associated with plerixafor mobilization of HSC.