Kathy R. Hogan

Development and validation of a decision-making algorithm to guide the use of plerixafor for autologous hematopoietic stem cell mobilization

Plerixafor is an inhibitor of CXCR-4 (CXC chemokine receptor-4)/SDF (stromal cell-derived factor)-1 binding used in combination with granulocyte colony-stimulating factor (G-CSF) for mobilization of autologous peripheral blood hematopoietic stem cells (HSCs). We developed a data-generated, cost-saving decision-making algorithm that uses the CD34+ count in the peripheral blood on the fourth day of G-CSF administration (PB-CD34+), and the collection target (T-CD34+) to decide between continuing G-CSF only (G approach) or adding plerixafor to the mobilization regimen (G+P approach) aiming at the lowest cost. The G+P approach was more cost-effective with lower PB-CD34+. It was possible to determine, for each T-CD34+, the maximum PB-CD34+ for which the G+P approach is cost-effective, generating an algorithm for the use of plerixafor. We validated this algorithm in a cohort of 34 patients undergoing HSC mobilization. In all, 11 patients completed collection on the G approach and 23 patients on the G+P approach, with 91% of the patients completing collection within the predicted number of apheresis sessions. All patients who underwent transplantation engrafted with minimal differences in engraftment time between G and G+P approaches. This validated algorithm provides a potential cost-saving decision tool for the use of plerixafor in autologous HSC mobilization.

Growth factor and patient-adapted use of plerixafor is superior to CY and growth factor for autologous hematopoietic stem cells mobilization

The ideal method to mobilize autologous hematopoietic stem cells (AHSCs) in patients with lymphoma or multiple myeloma remains to be determined. The use of plerixafor, added to growth factor, may overcome the limitations to the use of growth factor mobilization without chemotherapy. We developed and validated a cost-based decision-making algorithm that uses the CD34+ cell count in the peripheral blood on the fourth day of G-CSF administration and the target CD34+ cell count for the specific patient to decide on the use of plerixafor (MUSC algorithm). We compared this approach (MA cohort) with a historical cohort of patients undergoing mobilization with CY 2000 mg/m2 followed by G-CSF and GM-CSF (CY cohort). Fifty individuals are included in the MA cohort and 81 in the CY cohort. The mobilization failure rate was 2% in the MA cohort vs 22% in the CY cohort (P=0.01). Fewer patients in the MA cohort than in the CY cohort had infectious complications during mobilization requiring hospitalization (2 vs 30% P<0.01). There was significant shortening in the median number of days between starting mobilization and undergoing transplantation in the MA cohort (14 vs 43 days, P<0.01). In conclusion, growth factor and patient-adapted use of plerixafor provides safer hematopoietic stem cell mobilization and faster access to AHSC transplantation.

Growth factor plus preemptive ('just-in-time') plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure

Lenalidomide is associated with suboptimal autologous hematopoietic stem cell (AHSC) mobilization. We hypothesized that growth factor plus preemptive plerixafor is an effective strategy for AHSC mobilization in multiple myeloma (MM) despite prior exposure to lenalidomide. We retrospectively reviewed patient characteristics and mobilization outcomes of 89 consecutive MM patients undergoing first mobilization with filgrastim or pegfilgrastim +/− preemptive plerixafor using a previously validated algorithm based on day 4 peripheral blood CD34+ cell count (PB-CD34+) and mobilization target. Outcomes were analyzed according to the extent of prior exposure to lenalidomide: no prior exposure (group A, n=40), 1– 4 cycles (group B, n=30) and >4 cycles (group C, n=19). Multivariate analysis yielded only age and number of cycles of lenalidomide as negatively associated, and mobilization with pegfilgrastim as positively associated with higher PB-CD34+. Only 45% of patients in group A required plerixafor vs 63% in groups B and 84% in C, P=0.01. A higher proportion of patients in group A (100%) met the mobilization target than in groups B (90%) or C (79%), P=0.008. All patients yielded at least 2 × 106 CD34+/kg. Growth factor mobilization with preemptive plerixafor is an adequate upfront mobilization strategy for MM patients regardless of prior exposure to lenalidomide.

Beyond CD34+ cell dose: impact of method of peripheral blood hematopoietic stem cell mobilization (granulocyte-colony-stimulating factor [G-CSF], G-CSF plus plerixafor, or cyclophosphamide G-CSF/granulocyte-macrophage [GM]-CSF) on number of colony-forming unit-GM, engraftment, and Day +100 hematopoietic graft function.

BACKGROUND: The dose of CD34+ cells/kg in the mobilized peripheral blood product is the main determinant of neutrophil and platelet (PLT) engraftment after autologous hematopoietic stem cell transplantation (AHSCT). Whether the method of mobilization, namely, granulocyte–colony‐stimulating factor (G‐CSF) alone (G), G‐CSF plus plerixafor (G+P), or cyclophosphamide + G/granulocyte‐macrophage (GM)‐CSF (Cy+G/GM), independently affects number of colony‐forming unit (CFU)‐GM, engraftment, and hematopoietic graft function is unknown.

Pegfilgrastim- versus filgrastim-based autologous hematopoietic stem cell mobilization in the setting of preemptive use of plerixafor: efficacy and cost analysis.

BACKGROUND: Plerixafor enhances the ability of filgrastim (FIL) to mobilize CD34+ cells but adds cost to the mobilization. We hypothesized that replacing weight‐based FIL with flat‐dose pegfilgrastim (PEG) in a validated cost‐based mobilization algorithm for patient‐adapted use of plerixafor would add convenience without increased cost.