Successful peripheral blood stem cell mobilization with a cost-efficient single fixed-dose plerixafor schedule in poor mobilizers

Abstract

Plerixafor, although costly, is added to mobilizing chemotherapy and G-CSF to overcome poor stem cell mobilization. We demonstrate that it can be safely administered mostly once as a single dose in preemptive and rescue settings, leading to apheresis yields of >2 and >4×10 CD34 + cells/kg body weight (bw) in 83% and 48%, respectively. Of note, 35/46 (76%) patients showed a substantial benefit with increased peripheral blood (PB) CD34 + cells prior to apheresis (8.84 vs. 1.72/μl, p < .001), and 5-fold increased CD34 + cells collected per single apheresis (2.25 vs. 0.43 × 10 CD34+/kg bw, respectively, p < .001). Patients profiting most (76%) vs. less (24%) had >5 vs. <5/μl PB CD34 + cells before plerixafor application, respectively, thus careful patient selection in the latter group is advised. To the best of our knowledge, this is the first report demonstrating that favorable apheresis results can be obtained using this cost-efficient, single fixed-dose plerixafor schedule.

CXCL12 and CXCR7 are relevant targets to reverse cell adhesion‐mediated drug resistance in multiple myeloma

“…The binding of CXCL12 to CXCR4 directly promotes PC survival and facilitates CAM-DR (Alsayed et al, 2007;Roccaro et al, 2014Roccaro et al, , 2015. Current BMM-targeting agents, such as the stem cell mobilizing CXCR4 antagonist plerixafor, a small molecule bicyclam derivative which binds to CXCR4, or the anti-CXCL12 L -ribonucleotide NOX-A12 (olaptesed pegol), are being assessed in in vitro and in vivo analyses, including phase I/II clinical trials (Hoellenriegel et al, 2014;Ludwig et al, 2014Ludwig et al, , 2017Roccaro et al, 2015;Greil et al, 2017). Current BMM-targeting agents, such as the stem cell mobilizing CXCR4 antagonist plerixafor, a small molecule bicyclam derivative which binds to CXCR4, or the anti-CXCL12 L -ribonucleotide NOX-A12 (olaptesed pegol), are being assessed in in vitro and in vivo analyses, including phase I/II clinical trials (Hoellenriegel et al, 2014;Ludwig et al, 2014Ludwig et al, , 2017Roccaro et al, 2015;Greil et al, 2017).…”

“…Dissecting CXCL12-dependent cell trafficking and targeting the CXCL12/CXCR4-axis represents a promising therapeutic approach, particularly in RRMM with advanced BM microenvironment (BMM) involvement (Stessman et al, 2013). Current BMM-targeting agents, such as the stem cell mobilizing CXCR4 antagonist plerixafor, a small molecule bicyclam derivative which binds to CXCR4, or the anti-CXCL12 L -ribonucleotide NOX-A12 (olaptesed pegol), are being assessed in in vitro and in vivo analyses, including phase I/II clinical trials (Hoellenriegel et al, 2014;Ludwig et al, 2014Ludwig et al, , 2017Roccaro et al, 2015;Greil et al, 2017).…”

Comparison and cost analysis of three protocols for mobilization and apheresis of haematopoietic progenitor cells

“…Protocol 3 allowed us to obtain a significantly greater number of CD34+ cells than the other protocols: 7.93 × 10 6 CD34+ cells/kg vs 5.3 × 10 6 CD34+ cells/kg (protocol 1) and 4.28 × 10 6 CD34+ cells/kg (protocol 2). In other studies, this fact has also been suggested, either with the introduction of plerixafor [22][23][24][25][26] or with LVL. 2 In our country (Spain), there are no cost-benefit studies of mobilization protocols.…”

Reduced‐dose plerixafor as a mobilization strategy in autologous hematopoietic cell transplantation: a proof of concept study

“…However, most of these patients have been previously exposed to chemotherapy, radiation, or medications that affect bone marrow function; therefore, obtaining the necessary number of HSCs is a challenge in these patients. Although the optimal amount of CD34+ cells for autologous transplant is 5 × 10 6 /kg, a dose of at least 2 × 10 6 /kg CD34+ cells is required to ensure engraftment, lower doses may delay recovery of blood cells . Many risk factors have been associated with poor stem cell mobilization, including age, obesity, the underlying diagnosis (myeloma and lymphoma), previous radiotherapy or chemotherapy, disease status, among others .…”

“…Although the minimum number of cells required to guarantee engraftment is unknown, most authors agree that 2 × 10 6 /kg is sufficient, as lower doses may delay platelet and neutrophil engraftment . Lymphoma and myeloma are the most frequent contemporary indications of ASCT, with peripheral blood as the preferred source of HSCs for its faster hematopoietic and immune reconstitution, lower cost and greater donor comfort . However these diagnoses are associated with poor cell mobilization and unsuccessful peripheral blood stem cell (PBSC) collection, which can occur in 23%‐40% of cases .…”