Comparison of two autologous hematopoietic stem cell mobilization strategies in patients with multiple myeloma: CE plus G-CSF versus G-CSF only: A single-center retrospective analysis.

BACKGROUND: Despite recent advances in the treatment of multiple myeloma, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains an essential therapeutic keystone. As for the stem cell mobilization procedure, different regimens have been established, usually consisting of a cycle of chemotherapy followed by application of granulocyte-colony stimulating factor (G-CSF), although febrile neutropenia is a common complication. Following national guidelines, our institution decided to primarily use G-CSF only mobilization during the COVID-19 pandemic to minimize the patients' risk of infection and to reduce the burden on the health system. STUDY DESIGN AND METHODS: In this retrospective single-center analysis, the efficacy and safety of G-CSF only mobilization was evaluated and compared to a historic control cohort undergoing chemotherapy-based mobilization by cyclophosphamide and etoposide (CE) plus G-CSF. RESULTS: Although G-CSF only was associated with a higher need for plerixafor administration (p < .0001) and a higher number of apheresis sessions per patient (p = .0002), we were able to collect the target dose of hematopoietic stem cells in the majority of our patients. CE mobilization achieved higher hematopoietic stem cell yields (p = .0015) and shorter apheresis sessions (p < .0001) yet was accompanied by an increased risk of febrile neutropenia (p < .0001). There was no difference in engraftment after ASCT. DISCUSSION: G-CSF only mobilization is a useful option in selected patients with comorbidities and an increased risk of serious infections, especially in the wintertime or in future pandemics.

MEdical Database AnaLysIS of Japanese multiple myeloma patienTs with apheresis #2 (MEDALIST-2): the impact of plerixafor use on costs and healthcare resources during mobilization and stem cell transplantation.

Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.

Prolonged Lenalidomide Induction Does Not Significantly Impair Stem Cell Collection in Multiple Myeloma Patients Mobilized With Cyclophosphamide or Plerixafor: A Report From The Covid Era.

INTRODUCTION: Induction therapy for multiple myeloma is traditionally capped at 6 cycles of lenalidomide due to concerns that longer treatment compromises the ability to collect sufficient stem cells for autologous stem cell transplantation (ASCT). However, during the COVID-19 pandemic, many of our patients received prolonged lenalidomide induction due to concerns about proceeding to ASCT. We investigated whether prolonged induction with lenalidomide affects the efficacy of stem cell collection among patients mobilized with cyclophosphamide and/or plerixafor. PATIENTS AND METHODS: This single center, retrospective study included patients who were treated with lenalidomide induction regimens, received mobilization with cyclophosphamide or plerixafor, and underwent apheresis in preparation for ASCT. 94 patients were included, 40 of whom received prolonged induction with >6 cycles of lenalidomide containing regimen. RESULTS: Patients who received prolonged induction were more likely to require >1 day of apheresis (38% vs. 15%; OR 3.45; P = .0154), and there was a significant correlation between the duration of lenalidomide treatment and the apheresis time required to collect sufficient cells for transplant (R2 = 0.06423, P = .0148). However, there was no significant difference between patients who received prolonged induction and those who did not with respect to CD34+ stem cell yields at completion of apheresis (9.99 vs. 10.46 cells/Kg, P = .5513) or on the first day of collection (8.29 vs. 9.59 cells/Kg, P = .1788). CONCLUSION: Among patients treated with >6 cycles of lenalidomide, mobilization augmented with cyclophosphamide and/or plerixafor will likely facilitate sufficient stem cell harvest to permit ASCT.

Multiple Myeloma: Risk Adapted Use of Plerixafor for Stem Cell Mobilization Prior to Autologous Stem Cell Transplantation is Effective and Cost Efficient.

BACKGROUND: We used plerixafor in 'a risk adapted approach' for stem cell mobilization for multiple myeloma (MM) patients prior to autologous stem cell transplantation (ASCT). PATIENTS AND METHODS: Between January, 2017 and December, 2019 105 consecutive patients of MM were recruited (Study Cohort). Patients received inj G-CSF 10 µg/kg in 2 divided doses for 5 days. Day 4 peripheral blood (PB) CD34+ count was used as a guide; if count was < 20 cells/µl, patients received plerixafor. For those with ≥ 20 cells/µl apheresis was commenced on day 5. We compared their outcome with 156 MM patients transplanted between 2012 and 2016 with G-CSF mobilized PB stem cells (Control Cohort). Primary end point was to collect ≥2.0  ×  106 CD34+ cells/kg (minimal harvest). Secondary end points were: no of apheresis sessions, percentage of patients with optimal stem cell harvest (≥4.0  ×  106 CD34+ cells/kg) and cost analysis. An intent to treat analysis was done. RESULT: 96.2% of patients achieved ≥ 2.0  ×  106 CD34+ cells/kg in the study cohort vs. 87.2% in the control cohort, P < .01. Mean apheresis sessions were 1.5 vs. 1.7 respectively, P < .014 . Optimal stem cell harvest was 29.5% vs. 16%,P = .23. Days for neutrophil engraftment (P < 0.025) and for IV antibiotics (P < .0017) were favorable for the study cohort. Incremental cost effectiveness ratio was $ 15.80/- and $ 10.56/- per 1% increase to achieve a minimal and optimal harvest. CONCLUSION: Plerixafor in this risk adapted strategy resulted in successful mobilization, decreased time to engraftment and was cost effective.

Successful "on-demand" plerixafor for autologous peripheral blood stem-cells transplantation for relapsed/refractory germ cell tumors.

BACKGROUND: Germ cell tumors represent, among solid cancers, a potentially curable disease even if up to 20% to 30% of patients (pts) relapse after first-line treatment especially considering intermediate and poor prognosis groups. In this scenario, patients are candidates for high-dose chemotherapy and autologous stem-cells transplantation as second-line treatment even though stem-cells mobilization potential can be affected by several cycles and regimens of chemotherapy. To date, plerixafor is authorized in poor mobilizer adult pts diagnosed with lymphoma or multiple myeloma and in pediatric solid tumors or lymphoma. Therefore, the use of plerixafor in adult pts with relapsing/refractory GCT is still off label. MATERIALS AND METHODS: In our study, we describe mobilization and collection of peripheral blood stem cells for 10 pts with germ cell tumors. Six patients underwent plerixafor administration since classified as poor mobilizers based on WBC count (>5.000/µL) and CD34+ cell count (<15/µL) the day before apheresis procedure. RESULTS: On the first day of apheresis, plerixafor administration in poor mobilizers made possible a remarkable boost of CD34+ cells in such a way to overlap that of good mobilizers' (32/µL vs 35/µL, respectively, P > .05). CONCLUSION: Therefore, in our experience, plerixafor made a good fraction of poor mobilizer patients eligible for mobilization and collection and able to undergo the predicted autologous stem-cells transplantation; thus, the lack of access to the use of plerixafor in this setting of patients risks jeopardizing an effective treatment, especially in case of poor prognosis.

Subacute AMD3100 Treatment Is Not Efficient in Neonatal Hypoxic-Ischemic Rats.

BACKGROUND AND PURPOSE: Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE. METHODS: P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively. RESULTS: AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment. CONCLUSIONS: These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model.

Posttransplant blockade of CXCR4 improves leukemia complete remission rates and donor stem cell engraftment without aggravating GVHD.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematological malignancies, but relapse resulting predominantly from residual disease in the bone marrow (BM) remains the major cause of treatment failure. Using immunodeficient mice grafted with laboratory-generated human B-ALL, our previous study suggested that leukemia cells within the BM are resistant to graft-versus-leukemia (GVL) effects and that mobilization with CXCR4 antagonists may dislodge leukemia cells from the BM, enabling them to be destroyed by GVL effects. In this study, we extended this approach to patient-derived xenograft (PDX) and murine T-ALL and AML models to determine its clinical relevance and effects on GVHD and donor hematopoietic engraftment. We found that posttransplant treatment with the CXCR4 antagonist AMD3100 significantly improved the eradication of leukemia cells in the BM in PDX mice grafted with B-ALL cells from multiple patients. AMD3100 also significantly improved GVL effects in murine T-ALL and AML models and promoted donor hematopoietic engraftment in mice following nonmyeloablative allo-HCT. Furthermore, posttransplant treatment with AMD3100 had no detectable deleterious effect related to acute or chronic GVHD. These findings provide important preclinical data supporting the initiation of clinical trials exploring combination therapy with CXCR4 antagonists and allo-HCT.

Single-center results reporting improved hematopoietic stem cell mobilization success in pediatric and young adult patients with solid tumors and lymphoma.

BACKGROUND: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an established treatment for pediatric and young adult patients with solid tumors and lymphomas. Plerixafor is a CXC chemokine receptor type 4 (CXCR4) antagonist that can be used with granulocyte colony stimulating factor (G-CSF) to amplify the mobilization of hematopoietic stem cells (HSCs). METHODS: We performed a retrospective analysis of 167 pediatric solid tumor and lymphoma patients from January 2010 to July 2020 in whom HSCs were mobilized using G-CSF alone or with plerixafor. RESULTS: Thirteen heavily pretreated patients (33.3%) required twice-daily dosing of G-CSF compared to five patients (3.9%) in the not heavily pretreated group (p = .0005). Fourteen heavily pretreated patients (35.9%) required plerixafor compared to four patients (3.1%) in the comparison cohort (p = .0002). The number of mobilization days was similar between both cohorts, with 5 days (range 3-11 days) in the heavily pretreated group and 5 days (range 3-13 days) in the not heavily pretreated group (p = .55). The number of harvest days was 2 days (range 1-5 days) in the heavily pretreated group and 1 day (range 1-4 days) in the not heavily pretreated group (p = .0025). The final cluster of differentiation (CD)34+ /kilogram (kg) count was 9.52 × 106 /kg among heavily pretreated patients compared to 34.99 × 106 /kg CD34+ cells in the comparison group (p < .0001). Three heavily pretreated patients (7.7%) failed HSC mobilization. CONCLUSIONS: Patients at the highest risk for poor HSC mobilization can be successfully treated with more frequent G-CSF dosing or G-CSF with plerixafor in a large majority of cases.

Addition of plerixafor for mobilization of stem cells with bortezomib is feasible in dialysis-dependent multiple myeloma.

Plerixafor and bortezomib have recently been used in autologous stem cell collection to increase the amount of stem cells collected. However, no reports have described the combined use of plerixafor and bortezomib in cases of dialysis-dependent multiple myeloma. The dialysis-dependent multiple myeloma patient in the present study had a small amount of CD34-positive cells with plerixafor and filgrastim, and also with bortezomib and cyclophosphamide. However, by adding plerixafor to bortezomib and cyclophosphamide, collected CD34-positive cells were increased six-fold compared to the previous day. These findings suggest that the combination of plerixafor and bortezomib may be effective in those patients.

Radiotheranostics Using a Novel 225Ac-Labeled Radioligand with Improved Pharmacokinetics Targeting Prostate-Specific Membrane Antigen.

225Ac-based radiotheranostics targeting prostate-specific membrane antigen (PSMA) has induced impressive responses in patients with metastatic castration-resistant prostate cancer. To enhance the therapeutic effects of radioligands labeled with 225Ac (half-life: 10 days), a radioligand that shows longer tumor retention would be useful. Here, we designed and synthesized a straight-chain PSMA-targeting radioligand, PSMA-DA1, which includes an (iodophenyl)butyric acid derivative as an albumin binder (ALB). We performed preclinical evaluations of PSMA-DA1 as a tool for PSMA-targeting radiotheranostics using 111In, 90Y, and 225Ac. [111In]In-PSMA-DA1 demonstrated significantly greater tumor uptake and retention than a corresponding non-ALB-conjugated compound. In mice, single-photon emission computed tomography performed with [111In]In-PSMA-DA1 produced clear tumor images, and the administration of [90Y]Y-PSMA-DA1 or [225Ac]Ac-PSMA-DA1 inhibited tumor growth. [225Ac]Ac-PSMA-DA1 had antitumor effects in mice at a lower radioactivity level than [225Ac]Ac-PSMA-617, which has been reported to be clinically useful. These results indicate that PSMA-DA1 may be a useful PSMA-targeting radiotheranostic agent.

Latest update on chemokine receptors as therapeutic targets.

The chemokine system plays a fundamental role in a diverse range of physiological processes, such as homeostasis and immune responses. Dysregulation in the chemokine system has been linked to inflammatory diseases and cancer, which renders chemokine receptors to be considered as therapeutic targets. In the past two decades, around 45 drugs targeting chemokine receptors have been developed, yet only three are clinically approved. The challenging factors include the limited understanding of aberrant chemokine signalling in malignant diseases, high redundancy of the chemokine system, differences between cell types and non-specific binding of the chemokine receptor antagonists due to the broad ligand-binding pockets. In recent years, emerging studies attempt to characterise the chemokine ligand-receptor interactions and the downstream signalling protein-protein interactions, aiming to fine tuning to the promiscuous interplay of the chemokine system for the development of precision medicine. This review will outline the updates on the mechanistic insights in the chemokine system and propose some potential strategies in the future development of targeted therapy.

Role of CXCR4 in the progression and therapy of acute leukaemia.

CXCR4 is expressed on leukaemia cells and haematopoietic stem cells (HSCs), and its ligand stromal-derived factor 1 (SDF-1) is produced abundantly by stromal cells in the bone marrow (BM). The SDF-1/CXCR4 axis plays important roles in homing to and retention in the protective BM microenvironment of malignant leukaemia cells and normal HSCs. CXCR4 expression is regulated by multiple mechanisms and the level of CXCR4 expression on leukaemia cells has prognostic indications in patients with acute leukaemia. CXCR4 antagonists can mobilize leukaemia cells from BM to circulation, which render them effectively eradicated by chemotherapeutic agents, small molecular inhibitors or hypomethylating agents. Therefore, such combinational therapies have been tested in clinical trials. However, new evidence emerged that drug-resistant leukaemia cells were not affected by CXCR4 antagonists, and the migration of certain leukaemia cells to the leukaemia niche was independent of SDF-1/CXCR4 axis. In this review, we summarize the role of CXCR4 in progression and treatment of acute leukaemia, with a focus on the potential of CXCR4 as a therapeutic target for acute leukaemia. We also discuss the potential value of using CXCR4 antagonists as chemosensitizer for conditioning regimens and immunosensitizer for graft-vs-leukaemia effects of allogeneic haematopoietic stem cell transplantation.

Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective, multicenter study of a large series of patients.

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 106 CD34+ cells/kg) was 1 (range 1-4) and the median PLX administration time before apheresis was 11 h (range 1-18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1-5) and the mean number of CD34+ cells collected was 2.95 × 106/kg (range 0-30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/µL was 11 days (range 3-31) and the median time to platelet recovery >20 × 103/µL was 13 days (range 5-69). At 100 days after auto-HCT, the platelet count was 137 × 109/L (range 7-340), the ANC was 2.3 × 109/L (range 0.1-13.0), and the hemoglobin concentration was 123 g/L (range 79-165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34+ cell concentration on day +4 or low CD34+ cell yield on apheresis.

Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer.

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-ß induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.

Plerixafor combined with G-CSF for stem cell mobilization in children qualified for autologous transplantation- single center experience.

Failure of autologous peripheral blood CD34+ stem cells collection can adversely affect the treatment modality for patients with hematological and nonhematological malignant diseases where high dose chemotherapy followed by hematopoietic stem cell transplantation has become part of their treatment. Plerixafor in conjunction with G-CSF is approved for clinical use as a mobilization agent. The clinical efficacy of Plerixafor in CD34+ cells collection was analyzed in our institution. A total of 13 patients aged 1-15,5 years received Plerixafor in combination with G-CSF: 7 with neuroblastoma, 2 with Ewing's sarcoma and single patients with Hodgkin's lymphoma, germ cell tumor, retinoblastoma and Wilms tumor. Twelve patients (923%) achieved CD34+ cell counts of ≥ 20 × 106/L after 1-7 doses of Plerixafor. The average 9,9 - fold increase in number of CD34+ cells were achieved following the first dose and 429 - fold after second dose of plerixafor. Among the 13 patients, 12 yielded the minimum required cell collection of 2 × 106/kg within an average of 2 doses of Plerixafor. The mean number of apheresis days was 1.75. The median total number of collected CD34+ cells was 982 × 106/kg. Plerixafor enables rapid and effective mobilization, and collection of sufficient number of CD34+ cells.

First experience of the use of a generic of plerixafor in peripheral blood stem cell mobilization in multiple myeloma and lymphoma patients.

Mobilization failure in patients is a major therapeutic concern which makes subsequent ASCT impossible. A new growth factor called Plerixafor (Mozobil®) developed by the pharmaceutical industry (Sanofi-aventis, France), is a chemoreceptor antagonist, CXCR4 type, which disrupts the interaction of SDFI and CXCR4, thereby enhancing the effect of G-CSF mobilization and is especially indicated for mobilization failure. Currently, there is a generic of plerixafor developed by the pharmaceutical industry (Hetero Drugs Ltd, India). The brand name of this medicine is Mozifor®. The objective of this study was to evaluate if generic plerixafor has the same efficacy and safety as originator plerixafor when used with G-CSF in the mobilization of PBSCs for autologous ASCT in multiple myeloma (MM) and lymphoma failure patients. The 32 patients received plerixafor were divided in two groups. The first group concerns the 11 consecutive patients prospectively received generic plerixafor (Mozifor®) in the period between January to July 2020. These were compared with a retrospective control cohort (second group n = 21) who had been treated between 2009 and 2019 with originator plerixafor (Mozobil®). For the Mozifor® group, the mean CD34+ was 4.54x106/kg(1.56-6.79), the median time to achieve an absolute neutrophil count >0.5 G/L was 13 days (range: 8-21). The median time to self-sustained platelet count >20 G/L was 15 days (range: 8-24). For the Mozobil® group, the mean CD34+ was 3.1x106/kg (0.56-8.91) (p=0.86), the median time to achieve an absolute neutrophil count >0.5 G/L was 10 days (range 7-23). The median time to self-sustained platelet count >20 G/L was 13 days (range: 7-29). Our study showed that the generic of plerixafor was practically identical to that of the originator (Mozobil®) with no significant difference (p = 0.52). This study demonstrates the safety and feasibility of mobilization PBSC with generic plerixafor in ASCT in MM and lymphoma. Although these outcomes are encouraging, prospective comparison with other traditional auto-HCT regimens used for patients with MM and lymphoma is warranted.

Optimization of repeat plerixafor dosing for autologous peripheral blood stem-cell collection.

INTRODUCTION: Peripheral CD34+ cells may be mobilized using filgrastim alone or in combination with chemotherapy. The addition of plerixafor can be efficacious, though guidelines for repeat dosing are lacking. MATERIAL AND METHODS: This quality improvement project was initiated to generate guidelines for repeat plerixafor dosing after retrospective evaluation of data in adult patients undergoing autologous peripheral blood stem cell mobilization and collection. RESULTS: Analysis included 195 patients: 119 (61 %) with multiple myeloma and 76 (39 %) with lymphoma. Patients given at least one dose of plerixafor (n = 109) were further divided: Group 1) (A) goal of 3 × 10E6/kg and day 1 peripheral blood CD34+ count < 30 × 10E6/L, vs (B) ≥ 30 × 10 E6/L; Group 2) (A) goal of 6 × 10E6/kg and day 1 peripheral blood CD34+ count < 50 × 10E6/L or < 50 % of collection goal after day 1, vs (B) ≥ 50 % of collection goal after day 1. Ninety five percent of cases in Group 1B and 88 % of cases in Group 2B did not receive additional plerixafor doses and all of them achieved their collection goals. In contrast, those in Groups 1A and 2A required additional plerixafor dosing and some mobilizations/collections were futile. CONCLUSION: Based on these data, with consideration of collection goal, peripheral blood CD34+ count, and CD34+ cell bag count on collection day 1, we have generated institutional guidelines for collection initiation and repeat plerixafor dosing. Long term, we predict these guidelines will optimize pharmacy, apheresis, and stem cell processing resources while improving the patient experience.

A multicenter report on the safety and efficacy of plerixafor based stem cell mobilization in children with malignant disorders.

BACKGROUND: Pleraxifor for peripheral blood stem cell (PBSC) mobilization in children with malignancies is often given following failure of standard mobilization (SM) rather than as a primary mobilizing agent. STUDY DESIGN AND METHODS: In this retrospective multicenter study, we report the safety of plerixafor-based PBSC mobilization in children with malignancies and compare outcomes between patients who received plerixafor upfront with SM (Group A) with those who received plerixafor following failure of SM (Group B). In the latter pleraxifor was given either following a low peripheral blood (PB) CD34 (<20 cells/cu.mm) (Group B1) or as a second collection process due to an unsuccessful yield (CD34 + < 2 × 106 /kg) (Group B2) following failed SM and first apheresis attempts. RESULTS: The study cohort (n = 47) with a median age of 8 (range 0.6-21) year, comprised 19 (40%) Group A and 28 (60%) Group B patients (B1 = 12 and B2 = 16). Pleraxifor mobilization was successful in 87.2% of patients, similar between Groups A and B (84.2% vs 89.2%) and resulted in a median 4-fold increase in PB CD34. Median number of apheresis attempts was 2 in Groups A and B1 but 4 in Group B2. In Group B2, median total CD34+ yield post-plerixafor was 9-fold higher than after SM (P = .0013). Mild to moderate transient adverse events affected 8.5% of patients. Among patients who proceeded to autologous transplant (n = 39), all but one engrafted. CONCLUSION: Plerixafor-based PBSC collection was safe and effective in our cohort and supports consideration as a primary mobilizing agent in children with malignancies.

Addition of plerixafor to G-CSF in poor mobilizing healthy related donors overcame mobilization failure: An observational case series on behalf of the Grupo Español de Trasplante Hematopoyético (GETH).

Plerixafor (Mozobil, Sanofi) is approved for using in patients with lymphoma and multiple myeloma when steady-state mobilization strategies fail. Although off-label use of plerixafor in healthy related donors (HRD) is known, limited data are available and no recommendations exist to guide its use in this setting. With the aim of collecting data from HRDs who received plerixafor in our country, we designed an observational case series study within the Spanish Group of Hematopoietic Transplant and Cell Therapy (GETH). Plerixafor was administered subcutaneously to 30 HRDs at a median dose of 0.24 mg/Kg (interquartile range (IQR): 0.23-0.25) because mobilization failure after using mobilization with G-CSF (mobilization failure was defined as collection of <4.0 × 106 CD34+ cells/Kg recipient). All HRDs received G-CSF at a median dose of 11 µg/Kg/day (IQR: 10-12) for 4-5 days. Leukocytapheresis after G-CSF mobilization was performed in 23 (77 %) HRDs collecting a median of 1.6 × 106 CD34+ cells/Kg recipient weight (IQR: 0.9-2.5). Addition of plerixafor allowed the collection of a higher median number of CD34 cells (4.98 × 106 CD34+ cells/Kg recipient weight (IQR: 3.5-5.8)) when compared with the collection of CD34+ cells with G-CSF alone (p < 0.01). The final median total number of CD34+ cells collected was 6.1 × 106/Kg recipient weight (IQR: 4.8-7.3). Mild adverse events related with plerixafor administration were reported in 8 (27 %) donors. In conclusion, addition of plerixafor after G-CSF mobilization failure in HRDs allowed collecting higher number of CD34+ cells in comparison with steady-state mobilization.

Getting blood out of a stone: Identification and management of patients with poor hematopoietic cell mobilization.

Hematopoietic cell transplantation (HCT) has become a primary treatment for many cancers. Nowadays, the primary source of hematopoietic cells is by leukapheresis collection of these cells from peripheral blood, after a forced egress of hematopoietic cells from marrow into blood circulation, a process known as "mobilization". In this process, mobilizing agents disrupt binding interactions between hematopoietic cells and marrow microenvironment to facilitate collection. As the first essential step of HCT, poor mobilization, i.e. failure to obtain a desired or required number of hematopoietic cell, is one of the major factors affecting engraftment or even precluding transplantation. This review summarizes the available mobilization regimens using granulocyte-colony stimulating factor (G-CSF) and plerixafor, as well as the current understanding of the factors that are associated with poor mobilization. Strategies to mobilize patients or healthy donors who failed previous mobilization are discussed. Multiple novel agents are under investigation and some of them have shown the potential to enhance the mobilization response to G-CSF and/or plerixafor. Further investigation of the risk factors including genetic factors will offer an opportunity to better understand the molecular mechanism of mobilization and help develop new therapeutic strategies for successful mobilizations.