Two Strategies of Stem Cells Mobilization Using Plerixafor and Comparison of Grafts Obtained with and without It. Is Plerixafor Only a Mobilization Agent?
Authors: Zwiewka Michal , Stefanikova Zdenka , Masárová Katarína , Martinka Ján , Hrubiško Mikuláš , Pribulová Hana , Hapalová Jolana , Bojtárová Eva , Mistrik Martin 
Published: October 2019

Abstract
Abstract 4385

Introduction:
Successful autologous peripheral blood stem cell transplantation (aPBSCT) is critical for long-term survival and quality of life in patients with multiple myeloma (MM). Standard mobilization of PBSCs is in 15 to 20% of MM patients inefficient. Better mobilization response is achieved by adding plerixafor to current mobilization regimens. Based on studies it is possible to reduce these numbers to 2%.

Methodology:
During the period from 06/2009 to 08/2011 our department mobilized five patients with MM using plerixafor, of whom three were remobilized using standard G-CSF + plerixafor scheme (G+P) after a previous unsuccessful mobilization with cyclophosphamide + G-CSF (C+G). Two patients received plerixafor on demand in a failed first-line mobilization attempt (C+G+P).
Comprehensive statistical analysis of products mobilized with plerixafor (8 products) versus products obtained using C+G regime alone (40 products) was performed comparing smears, colony forming-units (CFUs) and immunophenotype profile. Time to mobilization, pretreatment, used mobilization regime and adverse effects of plerixafor regimes were also analyzed. The ultimate goal of every mobilization - successful transplantation - was also described and analyzed comparing composition of transplanted products with engraftment of white blood cells (WBC), neutrophil granulocytes and platelets.

Results:
Analysis of the plerixafor group only:
1. Both mobilization strategies (second-line G+P and first-line C+G+P) allowed to collect enough CD34+ cells for one (3 patients) or two (2 patients) transplants. Failure to mobilize using plerixafor has not been recorded. 3 patients successfully received transplants.
2. Based on an analysis of risk factors for determining poor mobilizer 3 patients could be mobilized preemptively using G+P scheme preventing use of controversial cyclophosphamide.
3. Adverse effects were mild and mainly related to G-CSF. In one patient mobilization was stopped after collecting 2.45 ×106/kg because of anxiety. However, we were unable to definitely connect anxiety symptoms to plerixafor.
4. There was a statistically significant increase of leukocytes in peripheral blood observed after adding plerixafor. In 3 patients it allowed the CD34+ cells to rise above 20/μl.
Comparative analysis of plerixafor group vs. group of patients mobilized with C+G:
1. Duration of cytopenia after transplantation was comparable and statistically not different.
2. Significantly higher numbers of CD19+ cells after plerixafor administration suggest a possible value of this drug in the treatment of diseases with this marker.
3. Significant reduction of toxic granulation after plerixafor administration may be a proof of lesser number of infectious complications.
4. Significantly lower numbers of younger cell forms and non-significantly higher numbers of mature cells in products mobilized with plerixafor prove a) no cytotoxic effect of plerixafor b) decreased regenerative potential of bone marrow in poor mobilizers even if chemotherapy is used.
5. Significantly lower numbers of CD34+ cells and CFUs in plerixafor mobilized products suggest a worse overall mobilization response in this group. However CFUs have shown to predict stem cells yield better than CD34+ cells alone.
6. The importance of a non-significant decrease in CD56+ cells in plerixafor mobilized products is unclear as co-expression of CD 38/56 does not show any differences.

Conclusions:
1. Preemptive first line mobilization with G+P seems to be an important strategy in predicted poor mobilizers which would otherwise be mobilized with C+G(+P). This prevents possible neutropenia and its complications. On demand first line G+P seems to be a good choice in patients that are mobilized with growth factors only as there is no risk of neutropenia.
2. We highly recommend the investigation of CFUs which usually predict stem cells yield better than CD34+ cells alone and may allow transplantation even if CD34+ cells are low.
3. Because aPBSCT is a therapeutic modality with clear benefit for patients with MM, we highly recommend the use of plerixafor in all MM patients where it is impossible to collect sufficient stem cells.
According to our investigation, we believe that plerixafor is only starting its career as a mobilization drug. Its most valuable potential may be in curative regimens of diseases which have affinity to bone marrow.

Disclosures:
No relevant conflicts of interest to declare.