Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft

Abstract

• Plerixafor is a safe, effective, rapid mobilizing agent when administered intravenously.• Lower rates of GVHD and CMV viremia with plerixaformobilized grafts may be related to a unique cellular composition of the graft.A single subcutaneous (SC) injection of plerixafor results in rapid mobilization of hematopoietic progenitors, but fails to mobilize 33% of normal allogeneic sibling donors in 1 apheresis. We hypothesized that changing the route of administration of plerixafor from SC to IV may overcome the low stem cell yields and allow collection in 1 day. A phase 1 trial followed by a phase 2 efficacy trial was conducted in allogeneic sibling donors. The optimal dose of IV plerixafor was determined to be 0.32 mg/kg. The primary outcome of reducing the failure to collect ‡2 3 10 6 CD34 1 /kg recipient weight in 1 apheresis collection to £10% was not reached. The failure rate was 34%. Studies evaluating the stem cell phenotype and gene expression revealed a novel plasmacytoid dendritic cell precursor preferentially mobilized by plerixafor with high interferon-a producing ability. The observed cytomegalovirus (CMV) viremia rate for patients at risk was low (15%), as were the rates of acute grade 2-4 graft-versus-host disease (GVHD) (21%). Day 100 treatment related mortality was low (3%). In conclusion, plerixafor results in rapid stem cell mobilization regardless of route of administration and resulted in novel cellular composition of the graft and favorable recipient outcomes. These trials were registered at clinicaltrials.

Factors predicting peripheral blood progenitor cell mobilization in healthy donors in the era of related alternative donors: Experience from a single center

“…We have focused on clinical and analytical variables that are available on the visit in which the mobilization is planned. With the development of the selective CXCR4 receptor antagonist plerixafor, detection of donors who might have poor mobilization results would be of special interest in order to plan a different mobilization strategy . Thus, we have recently communicated our experience with plerixafor off‐label in healthy donors who have failed to G‐CSF mobilization, without severe adverse effects and achieving enough CD34+ cells for the procedure .…”

“…Thus, none of the donors included in the study experienced mobilization failure, understood as less than 2 × 10 6 CD34+ cells/kg. Despite CD34+ ×10 6 cells per kg of recipient weight collected were lower in the poor mobilization group (P < 0.001), no differences on engraftment with neutrophils >5.0 × 10 9 /L (16 days (15-18) vs 16 days (14.5-18), P = 0.98) and platelets >20.0 × 10 9 /L (15.5 days (12-29) vs 13 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), P = 0.98) were found in the 148 transplants performed in our institution.…”

“…On the other hand, there is an increasing use of the selective CXCR4 receptor antagonist plerixafor, which is currently licensed for patients with multiple myeloma and non‐Hodgkin's lymphoma achieving poor mobilization with G‐CSF . With this drug available, there is a growing interest on identifying healthy donors who could benefit for its use (currently off‐label ) …”

“…15 With this drug available, there is a growing interest on identifying healthy donors who could benefit for its use (currently off-label). [16][17][18] In an attempt to understand factors influencing mobilization and collection of CD34+ cells in healthy, related and unrelated donors, including alternative haplo-identical donors, the yield of CD34+ cells from 159 donors from our center from 2008 to 2016 has been analyzed. With this different measurable outcome we tried to identify new variables predicting mobilization results and to confirm the value of the variables previously identified as predictors of collection results in healthy donors, exploring a logistic regression model to predict poor mobilization results.…”

Peripheral Blood Stem Cell Mobilization: a Look Ahead

“…Based on the potential benefit of a single day mobilization and apheresis procedure, administration of plerixafor as a standalone agent has been explored clinically, however the level of mobilization was not clinically effective, being significantly lower than G-CSF [15–17]. Moreover, a significant number of donors fail to mobilize sufficient cells even after multiple apheresis sessions or dose escalation and infusion [17]. Thus, the development of novel alternative strategies, particularly those that offer rapid mobilization and reduced costs remains an area of interest.…”