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Evidence describing the use of plerixafor in the off‐label population of relapsed/refractory germ cell tumors (GCT) is limited. We aim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as "rescue" (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as "preemptive" on Day 4 of granulocyte‐colony stimulating factor (G‐CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/μL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G‐CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing. [ABSTRACT FROM AUTHOR]

Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34+ cells/μL required to initiate apheresis. A median of 21.8 CD34+ cells/μL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34+ cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34+ cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34+ cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34+ cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols.

Patients with multiple myeloma (MM) scheduled for autologous stem cell transplantation must undergo autologous stem cell mobilization; unfortunately, however, many do not obtain an adequate collection yield. Despite the availability of plerixafor, its widespread and uniform use is limited by its cost, and consequently, many institutions have adopted various risk-adapted algorithms. We report our mobilization experience as we have modified our plerixafor algorithm to a more liberal one, with the expectation of greater collection efficiency and mobilization success with higher plerixafor use. A total of 344 mobilization attempts were analyzed over 3 time periods and using 3 different peripheral blood CD34+ cell counts to guide plerixafor use: <15/µL (n = 66), <20/µL (n = 130), and <40/µL (n = 148). The primary endpoints were evaluation of changes in mean plerixafor utilization and apheresis days and assessment of the impact on overall mobilization costs. Secondary endpoints were a description of the impact of lenalidomide use on mobilization and evaluation of the rate of mobilization failure. We found that mean plerixafor use increased from 1.32 to 1.65 to 1.74 doses per mobilization (P =.026) and the mean days of apheresis decreased from 2.15 to 2.17 to 1.89 days per mobilization for the <15/µL, <20/µL, and <40/µL cohorts, respectively (P =.011). The combined cost of plerixafor and apheresis procedures at a threshold of 40/µL is close to that at a threshold of 15/µL, while saving 26 apheresis days per 100 patients. In general, there were low rates of mobilization failure across all thresholds. Patients who received more than 6 cycles of lenalidomide demonstrated impaired mobilization and required more apheresis sessions (P <.013) and greater plerixafor use (P <.001) to achieve target stem cell yields. Overall, using plerixafor in patients with MM, with a day 4 pCD34 count of <40/µL is a reasonable and cost-effective strategy to optimize apheresis utilization. [ABSTRACT FROM AUTHOR]

The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration–approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed. The primary outcome was CD34 + cell mobilization success rates when plerixafor was administered 11 ± 2 hours (standard administration group) compared with 16 ± 2 hours before cell apheresis (early administration group), as defined as collection of  ≥2 × 10 6 CD34 + cells/kg. Secondary outcomes included the number of plerixafor therapy days required to collect a total of ≥2 × 10 6 CD34 + cells/kg, the number of apheresis cycles required to achieve ≥2 × 10 6 CD34 + cells/kg, the median CD34 + cells/kg collected in each apheresis session, and the rates of reported adverse events that occurred in the standard administration time group compared with the early administration time group. Of the 197 patients included, 114 patients received plerixafor 11 ± 2 hours before apheresis and 83 patients received plerixafor 16 hours ± 2 hours before apheresis. Ninety-four percent of patients in the early administration group achieved successful stem cell mobilization compared with 81.6% in the standard administration group ( P  = .0111). The median number of plerixafor days to reach the collection goal of  ≥2 × 10 6 CD34 + cells/kg was 1 day for each group ( P  = .323), and the median number of apheresis days to reach the collection goal was 2 days for the standard administration group compared with 1 day for the early administration group ( P  = .0156). Most adverse events were similar between the 2 groups except for fever, which occurred in 4.8% of the patients in the early administration group and none of the patients in the standard administration group. This study demonstrates plerixafor effectively mobilizes peripheral blood stem cells when given at an early administration time of 16 hours before apheresis compared with standard administration of 11 hours before apheresis. However, further prospective studies could strengthen these results. [ABSTRACT FROM AUTHOR]

Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34+ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34+ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34+ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34+ target in one collection ( P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort ( P = 0.001) as was the number of patients requiring more than one collection to reach their target ( P = 0.023). However, the average cost per patient was also significantly higher in the study cohort ( P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies. J. Clin. Apheresis 28:293-300, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell transplantation (HSCT) is an established treatment for relapsed chemotherapy sensitive non-Hodgkin's lymphoma (NHL) and an important component of anti-myeloma therapy. Recovery of bone marrow function after autologous HSCT is dependant on the dose of infused hematopoietic stem cells (HSCs) after bone marrow ablation. Despite the use of chemotherapy and granulocyte colony-stimulating factor (G-CSF) based mobilization regimens, some patients are unable to mobilize adequate numbers of CD34+ HSCs and cannot undergo potentially lifesaving autologous HSCT. Plerixafor (AMD3100 or Mozobil) is a newly licensed drug which is used with G-CSF to mobilize CD34+ HSCs for autologous HSCT, reducing apheresis requirements, and the rate of primary mobilization failure. Plerixafor and G-CSF "rescue" protocols allow the successful mobilization of HSCs in patients that have failed standard G-CSF based mobilization protocols. Hematopoietic stem cell biology and the use of Plerixafor in the management of NHL are reviewed. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell (HSC) transplantation is a treatment strategy for restoring normal hematopoietic function in patients with select hematologic malignancies. The number of CD34+ cells available for transplantation has been reported to be the strongest predictor of transplantation success, as measured by rapid and durable hematopoietic recovery. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used methods for stem cell mobilization. Unfortunately, 5-30% of patients do not respond to these agents. Plerixafor is a new HSC mobilizing drug that antagonizes the binding of chemokine stromal-cell-derived factor-1α (SDF-1α) to CXC chemokine receptor 4 (CXCR4). It is indicated in combination with G-CSF to mobilize HSC to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Results of clinical trials have shown that plerixafor plus G-CSF allow for the collection of a high yield of HSC with fewer apheresis sessions in patients with NHL and MM. Plerixafor has also shown promising results in small studies enrolling patients with Hodgkin's lymphoma. Moreover, for patients who fail G-CSF mobilization alone, plerixafor with G-CSF may be useful as a salvage mobilization strategy. Overall, plerixafor has been generally well tolerated with adverse effects classified as mild to moderate. The most common adverse effects reported in randomized clinical trials were injection site reactions and diarrhea, with approximately 33% of patients experiencing these effects. To our knowledge, clinical trials comparing G-CSF plus plerixafor with G-CSF plus chemotherapy and cost-effectiveness analyses have not been published; therefore, questions remain regarding the optimal role of plerixafor in the clinical practice setting. [ABSTRACT FROM AUTHOR]

Abstract: AMD3100 was found to inhibit HIV-1 and HIV-2 within the 1–10nM concentration range while not being toxic to the host cells at concentrations up to 500μM, thus achieving a selectivity index of approximately 100,000. The target of action was initially thought to be the viral envelope glycoprotein gp120. It appeared only to be the indirect target. The direct target of action turned out to be the co-receptor CXCR4 used by T-lymphotropic HIV strains (now referred to as X4 strains) to enter the cells. Initial (phase I) clinical trials undertaken with AMD3100, as a prelude to its development as a candidate anti-HIV drug for the treatment of AIDS, showed an unexpected side effect: an increase in the white blood cell counts. Apparently, AMD3100 specifically increased CD34+ hematopoietic stem cell counts in the peripheral blood. Stromal derived factor 1 (SDF-1), through its interaction with CXCR4, retains the stem cells in the bone marrow (a process referred to as “homing”), and AMD3100 specifically antagonizes this interaction. AMD3100 in combination with granulocyte colony-stimulating factor (G-CSF) resulted in the collection of more progenitor cells than G-CSF alone. At present, the major indication for clinical use of AMD3100 (Mozobil™) is the mobilization of hematopoietic stem cells from the bone marrow into the circulating blood for transplantation in patients with hematological malignancies such as non-Hodgkin''s lymphoma or multiple myeloma. [Copyright &y& Elsevier]

CCR5 and CXCR4 are structurally related chemokine receptors that belong to the superfamily of G-protein coupled receptors through which the HIV virus enters and infects cells. Both receptors are also related to HIV-associated neurocognitive disorders that include difficulties in concentration and memory, impaired executive functions, psychomotor slowing, depression and irritability, which are also hallmarks of the long-term sequelae of TBI. Moreover, A growing body of evidence attributes negative influences to CCR5 activation on cognition, particularly after stroke and traumatic brain injury (TBI). Here we investigated the effect of their blockage on motor and cognitive functions, on brain tissue loss and preservation and on some of the biochemical pathways involved. We examined the effect of maraviroc, a CCR5 antagonist used in HIV patients as a viral entry inhibitor, and of plerixafor (AMD3100), a CXCR4 antagonist used in cancer patients as an immune-modulator, on mice subjected to closed head injury (CHI). Mice were treated with maraviroc or plerixafor after CHI for the following 4 or 5 days, respectively. Neurobehavior was assessed according to the Neurological Severity Score; cognitive tests were performed by using the Y-maze, Barnes maze and the novel object recognition test; anxiety was evaluated with the open field test. The mice were sacrificed and brain tissues were collected for Western blot, pathological and immunohistochemical analyses. Both drugs enhanced tissue preservation in the cortex, hippocampus, periventricular areas, corpus callosum and striatum, and reduced astrogliosis)GFAP expression). They also increased the levels of synaptic cognition-related signaling molecules such as phosphorylated NR1 and CREB, and the synaptic plasticity protein PSD95. Both treatments also enhanced the expression of CCR5 and CXCR4 on different brain cell types. In summary, the beneficial effects of blocking CCR5 and CXCR4 after CHI suggest that the drugs used in this study, both FDA approved and in clinical use, should be considered for translational research in TBI patients. Unlabelled Image • Maraviroc and plerixafor, blockers of CCR5 and CXCR4, are FDA-approved drugs. • Maraviroc and plerixafor improve functional outcome after TBI in mice. • Maraviroc and plerixafor enhance tissue preservation and reduce inflammation. • Maraviroc and plerixafor upregulate synaptic cognition-related signaling molecules. • Maraviroc and plerixafor should be considered for translation in TBI patients. [ABSTRACT FROM AUTHOR]

Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34 + cells/μL required to initiate apheresis. A median of 21.8 CD34 + cells/μL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34 + cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34 + cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34 + cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34 + cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols., Competing Interests: J. Sevilla is a consultant and advisor and has received honorarium (Amgen, Novartis, Miltenyi, Sobi, Rocket Pharmaceuticals Inc.) and has licensed medicinal products from Rocket Pharmaceuticals Inc. S.N. and P.R. have licensed medicinal products and receive research funding and equity from Rocket Pharmaceuticals Inc. J.C.S.: Rocket Pharmaceuticals Inc.: consultant/incomes from licensed medicinal products/research funding/equity. J. Schwartz is Medical Director of Rocket Pharmaceuticals Inc. J. Surralles: service agreements (Rocket Pharmaceuticals Inc.). J.A.B.: Rocket Pharmaceuticals Inc.: consultant/incomes from licensed medicinal products/research funding/equity; Roche: honorarium; Pfizer: honorarium., (© 2021 The Author(s).)

Some malignant tumors in childhood require high-dose chemotherapy with stem cell support to achieve a cure. In patients heavily pretreated with myelosuppressive chemotherapy or irradiation, granulocyte colony-stimulating factor (G-CSF) may fail to mobilize stem cells from the bone marrow. Based on the experience with lymphoma and myeloma patients in whom peripheral blood-derived stem cell (PBSC) collection following mobilization with G-CSF failed, we successfully employed plerixafor in a 14-year-old female diagnosed with Ewing's sarcoma in early relapse treated with three lines of chemotherapy in whom PBSC could not be mobilized using either G-CSF alone or G-CSF following chemotherapy. No side effects were observed. Plerixafor may be an effective and safe agent for stem cell collection in pediatric patients with solid tumors, although new studies addressed to evaluate its effectiveness and safety are needed. J. Clin. Apheresis 27:260-262, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]