Impact of Different Mobilization Methods on Graft Composition and Outcome after Autologous Stem Cell Transplantation: Implications for Upfront Use of Plerixafor
Authors: Hill LaQuisa , Ukaegbu Oluchi C. , Savani Bipin N. , Sengsayadeth Salyka , Goodman Stacey , Brandt Stephen J. , Chinratanalab Wichai 
Published: October 2019

Abstract
Early lymphocyte recovery (ELC) is associated with improved outcomes of hematologic malignancies after autologous hematopoietic stem cell transplantation (auto-SCT). ELC, its composition and impact on outcome depends on many variables; however there is limited data on ELC after different mobilization strategies (G-CSF [G] vs. G + high dose cyclophosphamide [GC] vs. G + plerixafor [GP]). Results from a recent study showed that GP based mobilization can affect the number and subsets of immune competent cells contained in the graft. We studied whether these differences are associated with immune reconstitution (ELC), engraftment, or long-term outcomes.
We retrospectively identified patients undergoing auto-SCT at the Nashville VA Transplant Center between January 2000 and December 2010 in our CIBMTR database. Disease response was determined by standard CIBMTR response criteria. At our center, GP mobilization is reserved for patients who failed prior mobilization, to rescue G or GC mobilization, or as upfront usage in heavily pre-treated patients. Our patient cohort primarily included patients with multiple myeloma (MM) and lymphoma (LY).
We had evaluable data on 333 patients (MM=196; LY=127; others=10). Comparative analysis of different mobilization methods are summarized in Table 1. Median number of regimens pre-SCT for MM was 2 (range 1-5) and for lymphoma 2 (range1-7). Among LY patients, 60 (47.3%) patients were in complete remission (CR), 58 (45.7%) in partial remission (PR) and 9 (7%) had stable disease (SD). Among MM patients, 69 (35.2%) were in CR or very good partial remission (VGPR) pre-transplant, 105 (53.5%) were in PR, and 14 (7.1%) had SD. There was no significant difference between disease response status among different mobilization methods for either the MM or LY patients. A higher absolute WBC count was seen in grafts after GP mobilization compared to G or GC (p=0.01), despite a majority of patients having received GP mobilization after failed G or GC mobilization, or as a rescue regimen (n=20 [89%]). Similarly, absolute lymphocyte counts were higher in grafts mobilized after GP compared to G or GC (p=0.01). All patients engrafted and there was no difference in time to WBC or platelet engraftment between mobilization methods. Although the GP cohort was more heavily treated than the other cohorts (>2 regimens for GP 82%, vs. G 72% vs. GC 58% [p=0.02]), progression-free survival (PFS) and overall survival (OS) of G vs. GC vs. GP at 2-years was not significantly different between MM and LY cohorts (Table 1).
In summary, grafts mobilized with GP exhibited major differences in graft composition in conjunction with favorable post- transplant outcomes compared with grafts mobilized with G or GC. GP mobilization accelerated lymphocyte engraftment in this heavily treated group compared to G or GC. For patients proceeding to transplant heavily pre-treated, GP is a better mobilization method to ensure a robust graft is collected while avoiding the need for multiple stem cell collections and providing similar outcomes as patients less heavily treated and mobilized by G or GC. A prospective randomized controlled trial would elucidate whether progression free survival and overall survival might be improved by utilizing GP mobilization as a first-line therapy rather than as a rescue method.
Table 1. Graft composition and outcomes of different stem cell mobilization methods Variable G (n=97) GC (n=213) GP (n=23) P value Numbers of regimens pre-SCT, median 2.2 (95% CI, 2.0-2.4) 1.9 (1.8-2.0) 2.3 (1.9-2.7) 0.02 WBC in graft, median (range) 184.8 (12-777.7) 138.6 (11-542) 286.1 (186-400.3) 0.01 Absolute lymphocyte in graft (x103), median (range) 128.1 (13-321.1) 73.9 (3.4-433.6) 161.2 (47.4-302.0) 0.01 ANC >500 (days), median (range) 16 (11-25) 15 (7-86) 18 (13-24) 0.16 Platelets >20 (days), median (range) 13 (9-22) 12 (7-18) 12 (10-21) 0.07 OS (2 year) Lymphoma 74.5 77.9 72.7 0.054 Multiple myeloma 89.6 74.4 72 0.76 PFS (2 year) Lymphoma 58.2 57.6 46.1 0.1 Multiple myeloma 66.3 49 60 0.21

Disclosures
No relevant conflicts of interest to declare.