Risk Of Mobilization Failure Research Articles

Is an earlier strategy for harvesting peripheral blood stem cells in healthy allogeneic donors feasible?

IntroductionPeripheral blood stem cells (PBSC) mobilization with granulocyte colony stimulating factor (G-CSF) for healthy donors is generally performed at 5th day. However, earlier collection is sometimes feasible, raising the question of whether to initiate apheresis early to limit further G-CSF exposure, while considering the risk of mobilization failure. In the current study, we examined the factors predicting successful 4th day collection and developed a model that can be used practically. Patients and methodsThe study was carried out by obtaining the data of PBSC mobilizations performed between January 2009 and September 2022 in our transplantation center. ResultsA total of 141 healthy donors with a median donor age of 32 (18–64) were included. Adequate mobilization was achieved in 115 (81.6 %) patients. Median peripheral CD34 + cell count was 69.4/μL in the adequate mobilization group and 46/μL in the mobilization failure group (p < 0001). Multivariate analysis revealed that donor/recipient weight ratio and the 4th day peripheral CD34 + cell count≥ 50/μL were independent markers for 4th day collection success. A predictive model of our center including these parameters was available with 0.765 sensitivity and 0.968 specificity [(AUC):0.948 (95 % CI, 0.90–0.99), p < 0.001]. ConclusionThe result of the current study shows that peripheral 4th day collection can be performed in selected donors, taking into account peripheral CD34+ cell count and donor/recipient weight ratio. In addition, using these indicators, new predictive models can be created that may assist clinicians in daily practice.

Prior ESHAP treatment and risk for mobilization failure

Prior ESHAP treatment and risk for mobilization failure

Incorporating Reduced-Dose Plerixafor to a Preemptive Mobilization Algorithm Increases Access to Autologous Transplantation in a Limited-Resource Setting

Background Patients with lymphoma and myeloma undergoing autologous transplantation (ASCT) are at risk for mobilization failure. This limitation can be surpassed by combining multiple apheresis, cryopreservation and adding plerixafor to filgrastim. However, these strategies increase costs and are unaffordable for patients in low and middle-income countries (LMIC). We developed a mobilization strategy using peripheral CD34+ cell analysis and reduced-dose plerixafor (RD-plerixafor) to be used in a setting with limited resources. Objective To evaluate the efficacy of a mobilization algorithm defined by our ability to harvest ≥2 × 106Kg CD34+ cells in one apheresis session. Methods We performed a single-arm prospective study including adults with lymphoma or myeloma undergoing ASCT. Patients received filgrastim 5 μg/kg BID for 4 days followed by peripheral blood CD34+ cell analysis. We designed a mobilization algorithm hypothesizing that if the day 4 CD34+ pre-count was 5-10 cells/μL, a single RD-plerixafor dose at 0.12 mg/kg (11 hours prior to apheresis) would be sufficient to achieve a successful harvest (≥2 × 106/kg CD34+) in one large-volume session based on a prior study. Patients with Results Twenty-nine adults were included with a median day 4 CD34+cell pre-count of 15 cells/μL (1.4-88.7). N=19 received filgrastim (65.5%), N=6 received RD-plerixafor (20.7%) and N=4 full-dose plerixafor (13.8%). Median day 5 peripheral blood CD34+ increased to 34.3 cells/μL (10.8-107) (p Conclusion Incorporating RD-plerixafor into a mobilization algorithm is a safe and effective strategy that increases access to transplantation in patients with lymphoma and myeloma.

Incorporating Reduced-Dose Plerixafor to a Preemptive Mobilization Algorithm Increases Access to Autologous Transplantation in a Limited-Resource Setting

Background: Patients with lymphoma and myeloma undergoing autologous hematopoietic stem cell transplantation (ASCT) are at risk for mobilization failure, defined as the inability to harvest the minimum recommended 2x106/kg CD34+ cells prior to conditioning. This limitation can be surpassed by combining multiple apheresis sessions, cryopreservation and adding plerixafor to filgrastim. However, these strategies substantially increase transplant costs and are unaffordable for many patients in low and middle-income countries (LMIC). Furthermore, standard doses of plerixafor can lead to unnecessarily high CD34+ cell yields, leading to resource waste. We have previously shown that a reduced dose of plerixafor at 0.12 μg/kg is effective in a pilot trial. Consequently, we have incorporated RD-plerixafor to a mobilization algorithm using peripheral CD34+ cell analysis to be used in a setting with limited resources. Objective: To evaluate the efficacy of a decision-making mobilization algorithm in patients with lymphoma or myeloma defined by our ability to harvest at least 2x106Kg CD34+ cells in a single apheresis session. Methods: We performed a single-arm prospective study including consecutive adults diagnosed with lymphoma or myeloma undergoing ASCT in our institution. Patients received a mobilization regimen consisting of filgrastim 5 μg/kg BID for 4 days. On day 4 peripheral blood CD34+ cell flow cytometry analysis was performed. We designed a mobilization algorithm hypothesizing that if the day 4 CD34+ pre-count was 5-10 cells/μL, a single RD-plerixafor dose at 0.12 mg/kg (11 hours prior to apheresis) would be sufficient to achieve a successful harvest (≥2x106/kg CD34+) in one large-volume apheresis session based on a prior local study (Panel B). Patients with &lt;5 cells/μL received filgrastim plus a single dose of plerixafor 0.24 mg/kg and those with ≥10 cells/μL received filgrastim alone. Plerixafor vials were shared between 2 patients when possible. Day 5 peripheral CD34+ cell analysis was also performed. Cells were not frozen but were stored at 4ºC. Adverse effects, final CD34+ yield and probability of engraftment using 1-survival Kaplan Meier analysis were determined. This study was performed in accordance to the Declaration of Helsinki. Results: Twenty-nine patients were included. Baseline characteristics and outcomes are shown in Table 1. Median day 4 CD34+ cell pre-count was 15 cells/μL (range, 1.4-88.7). Following our algorithm n=19 patients received filgrastim (65.5%), n=6 received RD-plerixafor (20.7%) and n=4 full-dose plerixafor (13.8%). Median day 5 peripheral blood CD34+ increased to 34.3 cells/μL (range, 10.8-107) (Wilcoxon signed ranked p&lt;0.001), with a median increase of +28 cells/μL (+16.77-55.8) in the RD-plerixafor group. No severe adverse events were observed. We were able to successfully harvest 89.7% of patients using our algorithm with median final yield of 3.9x106 (1.7-12.3) CD34+cells/kg. Mobilization success rates were 94.7% for patients who recieved filgrastim alone, 83.3% for RD-plerixafor and 75% for full-dose plerixafor-treated patients. Optimal yields (≥5x106/kg) were achieved by 31% of patients using our strategy. Only three required a second apheresis session, and all underwent successful outpatient transplantation. One patient died due to hemorrhagic stroke on day +7. All remaining patients engrafted. Median probability of engraftment was estimated at 12 days for both neutrophils (95% CI 11.4-12.6) and platelets (95% CI 11.1-12.9) (Panel C). Female sex and prior treatment lines (continuous) were significantly associated to plerixafor requirement in a univariate regression analysis. Our strategy led to savings of $22,000 USD by lowering the plerixafor dose alone. Conclusion: Incorporating RD-plerixafor into a mobilization algorithm is a safe and effective strategy that increases access to transplantation in patients with lymphoma and myeloma at risk of harvesting failure. External validation of our decision-making algorithm is warranted. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.

Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 106 CD34+ cells/kg for a single or ≥5 × 106 CD34+ cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34+ cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34+ cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 106 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19+ and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

Advances in stem cell mobilization

Use of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic progenitor cells (HPCs) has largely replaced bone marrow (BM) as a source of stem cells for both autologous and allogeneic cell transplantation. With G-CSF alone, up to 35% of patients are unable to mobilize sufficient numbers of CD34 cells/kg to ensure successful and consistent multi-lineage engraftment and sustained hematopoietic recovery. To this end, research is ongoing to identify new agents or combinations which will lead to the most effective and efficient stem cell mobilization strategies, especially in those patients who are at risk for mobilization failure. We describe both established agents and novel strategies at various stages of development. The latter include but are not limited to drugs that target the SDF-1/CXCR4 axis, S1P agonists, VCAM/VLA-4 inhibitors, parathyroid hormone, proteosome inhibitors, Groβ, and agents that stabilize HIF. While none of the novel agents have yet gained an established role in HPC mobilization in clinical practice, many early studies exploring these new pathways show promising results and warrant further investigation.

Peripheral Blood Stem Cell Mobilization Tactics

To evaluate the methods and collection techniques currently used in stem cell mobilization for patients undergoing autologous transplantation. Literature search was performed through PubMed (1948-August 2009) and MEDLINE (1977-August 2009). Reference citations from publications identified were also reviewed. All literature identified was reviewed for inclusion. Original research and retrospective cohorts, along with previously published systematic reviews of stem cell mobilization and growth factors, were evaluated. Abstract data on plerixafor were also reviewed. Successful mobilization of an adequate number of progenitor cells can help ensure and improve time to neutrophil and platelet engraftment. A variety of methods have been studied to find the safest and most predictable mobilization of CD34+ progenitor cells, including use of single agents or the combinations of hematopoietic growth factors, chemotherapy, and a novel chemokine receptor 4 antagonist. Currently, granulocyte colony-stimulating factor (G-CSF) 10 microg/kg daily started 4 days prior to apheresis remains the standard of care for initial mobilization therapy. In patients who fail to mobilize or who are at high risk for mobilization failure, cyclophosphamide in conjunction with G-CSF may be used. Plerixafor, a novel chemokine receptor antagonist, in combination with G-CSF has demonstrated superiority for achieving collection goals compared to G-CSF alone in 2 Phase 3 trials. The optimal mobilization strategy is still unknown; however, colony-stimulating factors remain the most commonly used mobilization agents. Currently, chemotherapy or plerixafor in combination with G-CSF is a reasonable option in heavily pretreated and hard-to-mobilize patients with non-Hodgkin's lymphoma and multiple myeloma.

Pre-mobilization therapy blood CD34+ cell count predicts the likelihood of successful hematopoietic stem cell mobilization

We examined pre-mobilization blood CD34+ cell count to predict ability to mobilize adequate peripheral blood progenitor cells (PBPC) in 106 cancer patients and 36 allogeneic donors. Mean pre-mobilization therapy blood CD34+ cell count was 3.1 cells x 10(6)/l (s.d. = 3.9, r = 0.3-37) and mean CD34+ cells collected were 5.3 x 10(6) cells/kg/leukapheresis procedure (s.d. = 7.0, r = 0.03-53). Yields correlated with pre-mobilization CD34+ cells x 10(6)/l (r = 0.37, P-value < 0.0001); correlation was stronger in allogeneic donors (r = 0.56, P-value = 0.0004) and males (r = 0.46, P-value < 0.0001). Based on classification and regression tree multivariate analysis, the predictive value of pre-mobilization blood CD34+ cell count was confounded by other variables, including age, gender, mobilization regimen and malignancy type. We generated an algorithm to predict a minimum PBPC yield of 1 x 10(6) CD34+ cells/kg/leukapheresis procedure after mobilization. A threshold pre-mobilization blood CD34+ cell count of 2.65 cells x 10(6)/l was the most important decision point in predicting successful mobilization. Only 2% of subjects with pre-mobilization blood CD34+ cell counts > 2.65 cells x 10(6)/l did not achieve the minimum per apheresis, whereas 24% with pre-mobilization values below threshold had inadequate mobilization. Prospectively identifying individuals at risk for mobilization failure would allow for improved treatment planning, resource utilization and time saving.