Poor Mobilizing Lymphoma Patients Rescued By Addition of Plerixafor during Stem Cell Mobilization Have Equal Survival As Good Mobilizers When Given High Dose Therapy with Autologous Stem Cell Support
Authors: Josefsen Dag , Fløisand Yngvar , Holte Harald , Kvalheim Gunnar 
Published: November 2019

Abstract
High dose therapy (HDT) followed by autologous stem cell support is a curative treatment option in selected lymphoma patients. To obtain a quick and sustained engraftment after high dose therapy, a minimal number of 2x106 CD34+ cells/kg are preferable. However, in 15-20% of the lymphoma patients insufficient numbers of CD34+ cells are harvested, characterized as poor mobilizers. Furthermore, previous findings have shown that poor mobilizing lymphoma patients given HDT have a less favorable prognosis than good mobilizers. In recent years, new mobilizing agents including plerixafor, a CXCR4 antagonist, have been developed. Our previous findings have shown that with a low concentration of CD34+ cells (4-10 cells/µL) and a total white cell count >4x109/L, addition of plerixafor resulted in successful stem cell harvesting in these poor mobilizing patients.
In the present study, we have mobilized 37 poor-mobilizing lymphoma patients with addition of plerixafor from January 2010 to December 2014. Four patients were mobilized with G-CSF and plerixafor, whereas 33 patients were given plerixafor in addition to chemotherapy and G-CSF. Thirty four patients underwent a successful stem cell harvest and received high dose therapy. The patients were followed up after reinfusion of autologous stem cells with regard to short term and long term engraftment as well as relapse and death.
The day prior to harvest, the level of leukocytes was 12,6x109 cells/L (median; range3,3-65,2), and the CD34+ concentration was 5,7x106/L (median; range 1,9-12,4). Following plerixafor injection, the concentration of CD34+ cells increased to 23,4 x106/L (median; range 5,6-65,6). The patients were then harvested (median: 3,9x106 CD34+cells/kg; range: 1,5-7,3) with 1-2 days of apheresis, One of the patients received high dose therapy although we only obtained 1.8x106 CD34+cells/kg at stem cell harvest.
In the 34 lymphoma patients receiving high dose therapy followed by autologous stem cell support we observed that time to short term engraftment, defined by neutrophils >0.5x109/L and thrombocytes >20x109/L were 12 days (median; range 8-19) and 14 days (median; range 10-100) respectively. Furthermore, as an estimate of long term engraftment we examined the thrombocyte levels at day 100 after reinfusion. The median level was 132x109/L (range 27-398). Moreover, in contrast to previous findings we have observed durable responses with event free survival of 56% and overall survival of 67% (Median observation time without relapse: 19,5 months, range 0-64 months).
In conclusion, our findings show that addition of plerixafor is successful in mobilization of hematopoietic stem cells in poor mobilizing patients resulting in a quick and sustained engraftment as well as durable responses and similar prognosis as for good mobilizing lymphoma patients after high dose therapy with autologous stem cell support.

Disclosures
No relevant conflicts of interest to declare.