Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)—Polish compassionate use experience

Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (N = 23), non-Hodgkin’s lymphoma (N = 20), or Hodgkin’s lymphoma (N = 18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/μL (range of 0–121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0–4) aphereses were performed. A minimum of 2.0 × 106 CD34+ cells per kilogram of the patient’s body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67 × 106 CD34+ cells/kg b.w. (0–8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkin’s lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers

European data on stem cell mobilization with plerixafor in patients with nonhematologic diseases: an analysis of the European consortium of stem cell mobilization

BACKGROUND: Plerixafor with granulocyte–colonystimulating factor (G-CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty-three patients with germ cell tumor (n = 11), Ewing sarcoma (n = 6), Wiscott-Aldrich disease (n = 5), neuroblastoma (n = 4), and other nonhematologic diseases (n = 7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G-CSF (n = 21) or after chemotherapy and G-CSF (n = 12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2 ¥ 106/kg body weight (b.w.) CD34+cells (median, 5.0 ¥ 106/kg b.w. CD34+ cells; range, 2.0 ¥ 106-29.5 ¥ 106/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5 ¥ 106/kg b.w. CD34+ cells (range, 0.9 ¥ 106-1.8 ¥ 106/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3 ¥ 106/kg b.w. (range, 2.3 ¥ 106-6.7 ¥ 106/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9-12) and 15 (range, 10-25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G-CSF or chemotherapy and G-CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients

European data on stem cell mobilization with plerixafor in patients with nonhematologic diseases: an analysis of the European consortium of stem cell mobilization.

BACKGROUND: Plerixafor with granulocyte-colony-stimulating factor (G-CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty-three patients with germ cell tumor (n=11), Ewing sarcoma (n=6), Wiscott-Aldrich disease (n=5), neuroblastoma (n=4), and other nonhematologic diseases (n=7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G-CSF (n=21) or after chemotherapy and G-CSF (n=12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2 710(6)/kg body weight (b.w.) CD34+ cells (median, 5.0 710(6)/kg b.w. CD34+ cells; range, 2.0 710(6)-29.5 710(6)/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5 710(6)/kg b.w. CD34+ cells (range, 0.9 710(6)-1.8 710(6)/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3 710(6)/kg b.w. (range, 2.3 710(6)-6.7 710(6)/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9-12) and 15 (range, 10-25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G-CSF or chemotherapy and G-CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients

Higher BMI is not a barrier to stem cell mobilization with standard doses of plerixafor and G-CSF.

Letter to the Edito

European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization.

The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 7 10(6) CD34+ cells/kg: 81.6%; >5.0 7 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 7 10(6) CD34+ cells/kg: 64.8%; >5.0 7 10(6) CD34+ cells/kg: 12.6%; P2.0 7 10(6) CD34+ cells/kg: 81.5%; >5.0 7 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required

Higher BMI is not a barrier to stem cell mobilization with standard doses of plerixafor and G-CSF

Overweight and obesity are growing epidemiologic problems worldwide. Body mass index (BMI) defined as a person’s weight in kilograms divided by the square of his height in meters (kg/m2) is a simple measure in common use. According to the WHO definition, people with a BMI X25 kg/m2 are overweight and those with a BMI X30 kg/m2 are obese. A raised BMI is recognized as a major risk factor for cardiovascular diseases, diabetes and musculoskeletal disorders, and also for a number of cancers, including non-Hodgkin’s lymphoma and multiple myeloma.This, taken together with higher doses of plerixafor in overweight and obese patients, may contribute to the increased cost of the mobilization procedure. However, as it is not known how the excess of fatty tissue affects the distribution of the drug, as well as homing and engraftment of mobilized progenitor cells, this problem could be potentially overcome by calculating the dose of plerixafor and/or required dose of hematopoietic stem cells per kg of ideal body weight and not per kg of actual body weight in overweight and obese individual