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Adequate stem cell harvesting is required for autologous hematopoietic transplantation. In deficient mobilizer patients, the collection of stem cells can be challenging because of the impossibility of achieving satisfactory CD34 cell counts with GCSF + - chemotherapy. Plerixafor is a potent and expensive drug that promotes the release of stem cells from the medullary niche to the peripheral blood and allows satisfactory harvests. We performed a retrospective analysis of 370 patients with myeloma and lymphoma harvested at our institution. 99 % of patients achieved satisfactory apheresis using Plerixafor in 45 %. Satisfactory harvests were obtained in patients mobilized with GCSF or plerixafor. In patients who used plerixafor, it was necessary to perform fewer apheresis procedures (P = 0.05). In multivariate analysis, the only factor that predicted the need for plerixafor was the presence of less than 30,000 CD34 / ul on the day of apheresis (OR 0.3. p < 0.001). Since we adopted the plerixafor protocol guided by CD34 counts, the number of patients with harvest failure has decreased. In conclusion, the rational and standardized use of plerixafor favors satisfactory harvest in patients who require autologous transplantation in South-American patients.

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High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improved 5-year overall survival rates in relapsed/refractory germ cell tumors (GCTs) from 10% to 52%. Nearly 30% of GCT patients are deemed poor mobilizers after receiving several lines of prior therapy. There is limited data available regarding upfront plerixafor use in GCT patients. We predicted upfront plerixafor use would increase the amount of stem cells collected preventing subsequent mobilizations and improve time to curative therapy. A retrospective, single center, chart review of adult GCT patients who received plerixafor upfront for mobilization at a single center between January 1, 2013 and August 31, 2021 was performed. The primary objective was to evaluate the rate of successful peripheral blood CD34+ cell collections. Secondary objectives consisted of describing the impact of plerixafor use on mobilization and assessing auto-HSCT related outcomes. Sixteen patients received plerixafor upfront after an average of three prior lines of therapy (range: 2-5 lines). Successful collection (≥4 × 106 CD34+ cells/Kg collected within four days) was achieved in 15 (94%) patients in a median of one apheresis day (interquartile range: 1-2 days). All patients proceeded to an initial auto-HSCT and 12 patients (75%) completed both transplants as planned. Survival at 12 months was 50%. The significantly higher amount of CD34+ cells collected over less apheresis days demonstrated the clinical utility of upfront plerixafor and its potential to facilitate more efficient stem cell mobilization. There is a need for larger randomized studies with upfront plerixafor use in this unique patient population.

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INTRODUCTION: Although plerixafor in association with granulocyte colony-stimulating factor (G-CSF) can improve mobilization and collection of hematopoietic stem cells (HSC) by leukapheresis, cost may limit its clinical application. The present study systematically reviews economic evaluations of plerixafor plus G-CSF usage compared to G-CSF alone and compares different strategies of plerixafor utilization in multiple myeloma and lymphoma patients eligible for autologous HSC transplantation. AREAS COVERED: Relevant economic evaluations, partial or complete, were searched on PubMed, Embase, LILACS, and Cochrane Central Register of Controlled Trials for a period ending 30 June 2021. This systematic review was reported following the PRISMA Statement. Six economic evaluations were included, considering the use of upfront or just-in-time plerixafor compared to G-CSF alone or other plerixafor strategies. Most comparisons showed both increased cost and health benefits with the addition of plerixafor. Most analyses favored just-in-time plerixafor compared to upfront plerixafor, with a probable preference for broader cutoffs for just-in-time plerixafor initiation. EXPERT OPINION: Plerixafor is a potentially cost-effective technology in the mobilization of HSC in patients with multiple myeloma and lymphomas eligible for autologous HSC transplantation. There is a decreased number of leukapheresis sessions and remobilizations and a higher yield of CD34+ cells.

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BACKGROUND: Endothelial progenitor cells (EPCs) are immature cells able to proliferate and contribute to endothelial repair, vascular homeostasis, neovascularization, and angiogenesis. It therefore seems likely that circulating EPCs have therapeutic potential in ischemic and vascular diseases. In this study we evaluated the efficiency of EPC mobilization and collection by large volume leukapheresis in subjects with hematological diseases, treated with plerixafor in association with G-CSF. METHODS: Twenty-two patients with lymphoid malignancies underwent rHuG-CSF and plerixafor treatment followed by leukapheresis. Blood samples before and after treatment and apheresis liquid sample were taken and analyzed by flow cytometry in order to quantified EPC. RESULTS: The percentage of CD34+ cells and EPCs among circulating total nuclear cells (TNCs) increased significantly by approximately 2-fold and 3-fold, respectively, after plerixafor treatment. Consequently, the absolute number of CD34+ cells and EPCs were increased 4-fold after plerixafor treatment. The median PB concentration of EPCs before and after treatment were 0.77/µL (0.31-2.15) and 3.41/µL (1.78-4.54), respectively, P < .0001. The total EPCs collected per patient were 3.3×107 (0.8×107 -6.8×107 ). CONCLUSION: We have shown that plerixafor in combination with G-CSF allows the mobilization and collection of large amounts of EPCs along with CD34+ cells in lymphoid neoplasm patients. The possibility to collect and to store these cells could represent a promising therapeutic tool for the treatment of ischemic complications without the need of in vitro expansion.

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ABSTRACT Introduction: To study the efficacy and safety of single large volume leukapheresis by using generic G-CSF or G-CSF plus Plerixafor in achieving adequate stem cell yield and various factors influencing thereof in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant . Method: This prospective study was undertaken among 55 newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant and aged between 18 and 75 years. Mobilization and harvesting of stem cells were performed by using GCSF or GCSF plus Plerixafor and large volume leukapheresis, respectively. A stem cell yield of ≥2 × 106 kg-1 and the number of apheresis procedures were primary efficacy endpoints, while the ideal stem cells yield >5 × 106 kg-1, the engraftment day and D100 response/graft sustainability were secondary endpoints. Result: The primary endpoint was achieved in all cases in both the groups by using a single LVL leukapheresis procedure. Fulfillment of all the secondary endpoints was satisfactory and comparable in both the groups. Age, pre-apheresis CD34+ count and number of interruptions during the LVL were significant factors influencing the stem cell yield (p < 0.05). Adverse drug reactions during the apheresis and post-ASCT period were manageable. Conclusion: The LVL is safe and cost-effective in attaining a minimum of CD34+ cells in a single procedure with manageable adverse reactions. Judicious intervention during the procedure may be helpful in ensuring the adequate yield.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that leads to coronavirus disease (COVID-19) has put public health at risk in 2020. The spike protein (SP) in SARS-CoV-2 is primarily responsible for the attachment and entry of the virus into the cell, which binds to the angiotensin-converting enzyme 2 (ACE2). Owing to the lack of an effective therapy, drug repositioning is an opportunity to search for molecules with pharmacological potential for the treatment of COVID-19. In this study, three candidates with the potential to destabilize the SP-ACE2 complex are reported. Through molecular docking, 147 drugs were evaluated and their possible binding sites in the interface region of the SP-ACE2 complex and the SP of SARS-CoV-2 were identified. The five best candidate molecules were selected for molecular dynamics studies to observe changes in interactions between SP-ACE2 and ligands with the SP-ACE2 complex. Using umbrella sampling molecular dynamics simulations, the binding energy of SP with ACE2 (-29.58 kcal/mol) without ligands, and in complex with amprenavir (-20.13 kcal/mol), enalaprilat (-23.84 kcal/mol), and plerixafor (-19.72 kcal/mol) were calculated. These drugs are potential candidates for the treatment of COVID-19 as they destabilize the SP-ACE2 complex; the binding energy of SP is decreased in the presence of these drugs and may prevent the virus from entering the cell. Plerixafor is the drug with the greatest potential to destabilize the SP-ACE2 complex, followed by amprenavir and enalaprilat; thus, these three drugs are proposed for future in vitro and in vivo evaluations.

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INTRODUCTION: To study the efficacy and safety of single large volume leukapheresis by using generic G-CSF or G-CSF plus Plerixafor in achieving adequate stem cell yield and various factors influencing thereof in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant . METHOD: This prospective study was undertaken among 55 newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant and aged between 18 and 75 years. Mobilization and harvesting of stem cells were performed by using GCSF or GCSF plus Plerixafor and large volume leukapheresis, respectively. A stem cell yield of ≥2×106kg-1 and the number of apheresis procedures were primary efficacy endpoints, while the ideal stem cells yield >5×106kg-1, the engraftment day and D100 response/graft sustainability were secondary endpoints. RESULT: The primary endpoint was achieved in all cases in both the groups by using a single LVL leukapheresis procedure. Fulfillment of all the secondary endpoints was satisfactory and comparable in both the groups. Age, pre-apheresis CD34+ count and number of interruptions during the LVL were significant factors influencing the stem cell yield (p<0.05). Adverse drug reactions during the apheresis and post-ASCT period were manageable. CONCLUSION: The LVL is safe and cost-effective in attaining a minimum of CD34+ cells in a single procedure with manageable adverse reactions. Judicious intervention during the procedure may be helpful in ensuring the adequate yield.

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SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.

RESUMO Pacientes selecionados com certas neoplasias hematológicas e tumores sólidos têm o potencial de alcançar sobrevida de longo prazo com o transplante autólogo de células progenitoras hematopoéticas. A coleta dessas células no sangue periférico evita múltiplas aspirações de medula óssea, resulta em enxertia mais rápida, e permite o tratamento de pacientes com infiltração, fibrose ou hipocelularidade medular. Contudo, para o sucesso desse procedimento, é essencial mobilizar um número suficiente de células progenitoras da medula óssea para a circulação sanguínea. Por isso, um painel de especialistas brasileiros se reuniu com o objetivo de desenvolver recomendações para estratégias de mobilização adaptadas à realidade do sistema de saúde nacional, que pudessem contribuir para minimizar os riscos de falha, reduzir a toxicidade e melhorar a alocação de recursos financeiros.

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The use of high-dose chemotherapy with autologous support of hematopoietic progenitor cells is an effective strategy to treat various hematologic neoplasms, such as non-Hodgkin lymphomas and multiple myeloma. Mobilized peripheral blood progenitor cells are the main source of support for autologous transplants, and collection of an adequate number of hematopoietic progenitor cells is a critical step in the autologous transplant procedure. Traditional strategies, based on the use of growth factors with or without chemotherapy, have limitations even when remobilizations are performed. Granulocyte colony-stimulating factor is the most widely used agent for progenitor cell mobilization. The association of plerixafor, a C-X-C Chemokine receptor type 4 (CXCR4) inhibitor, to granulocyte colony stimulating factor generates rapid mobilization of hematopoietic progenitor cells. A literature review was performed of randomized studies comparing different mobilization schemes in the treatment of multiple myeloma and lymphomas to analyze their limitations and effectiveness in hematopoietic progenitor cell mobilization for autologous transplant. This analysis showed that the addition of plerixafor to granulocyte colony stimulating factor is well tolerated and results in a greater proportion of patients with non-Hodgkin lymphomas or multiple myeloma reaching optimal CD34(+) cell collections with a smaller number of apheresis compared the use of granulocyte colony stimulating factor alone.

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ABSTRACT The use of high-dose chemotherapy with autologous support of hematopoietic progenitor cells is an effective strategy to treat various hematologic neoplasms, such as non-Hodgkin lymphomas and multiple myeloma. Mobilized peripheral blood progenitor cells are the main source of support for autologous transplants, and collection of an adequate number of hematopoietic progenitor cells is a critical step in the autologous transplant procedure. Traditional strategies, based on the use of growth factors with or without chemotherapy, have limitations even when remobilizations are performed. Granulocyte colony-stimulating factor is the most widely used agent for progenitor cell mobilization. The association of plerixafor, a C-X-C Chemokine receptor type 4 (CXCR4) inhibitor, to granulocyte colony stimulating factor generates rapid mobilization of hematopoietic progenitor cells. A literature review was performed of randomized studies comparing different mobilization schemes in the treatment of multiple myeloma and lymphomas to analyze their limitations and effectiveness in hematopoietic progenitor cell mobilization for autologous transplant. This analysis showed that the addition of plerixafor to granulocyte colony stimulating factor is well tolerated and results in a greater proportion of patients with non-Hodgkin lymphomas or multiple myeloma reaching optimal CD34+ cell collections with a smaller number of apheresis compared the use of granulocyte colony stimulating factor alone.

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