1.
Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield
Farhadfar, N., Hsu, J. W., Logan, B. R., Sees, J. A., Chitphakdithai, P., Sugrue, M. W., Abdel-Azim, H., Anderlini, P. N., Bredeson, C., Chhabra, S., et al
Blood advances. 2020;4(4):706-716
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Abstract
There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI. Using the Center for International Blood and Marrow Transplant Research database, we evaluated the impact of donor BMI on G-CSF-mobilized PBSC yield in healthy unrelated donors. We examined 20 884 PBSC donations collected at National Marrow Donor Program centers between 2006 and 2016. We found significantly higher collection yields in obese and severely obese donors compared with normal and overweight donors. An increase in average daily G-CSF dose was associated with an increase in stem cell yield in donors with normal or overweight BMI. In contrast, an increase in average daily G-CSF dose beyond 780 mug per day in obese and 900 mug per day in severely obese donors did not increase cell yield. Pain and toxicities were assessed at baseline, during G-CSF administration, and postcollection. Obesity was associated with higher levels of self-reported donation-related pain and toxicities in the pericollection and early postdonation recovery periods. This study suggests a maximum effective G-CSF dose for PBSC mobilization in obese and severely obese donors, beyond which higher doses of G-CSF add no increased yield.
2.
Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario
Kouroukis, C. T., Varela, N. P., Bredeson, C., Kuruvilla, J., Xenocostas, A.
Current Oncology. 2016;23(4):e409-30
Abstract
BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10-18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. METHODS The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. RECOMMENDATIONS These recommendations apply to adult patients considered for asct: Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available. For patients with a low peripheral blood CD34+ cell count (for example, <10/muL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization. It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.
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Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies
Sheppard, D., Bredeson, C., Allan, D., Tay, J.
Biology of Blood & Marrow Transplantation. 2012;18(8):1191-203
Abstract
Collection of adequate hematopoietic stem cells (HSCs) is necessary for successful autologous transplantation; however, a proportion of patients fail to collect the minimum number of cells required. We summarized the efficacy and safety of HSC mobilization strategies. We performed a systematic review of randomized controlled trials comparing HSC mobilization strategies before autologous transplantation for hematologic malignancies. The primary outcome was CD34+ cell yield. Secondary outcomes included number of aphereses, proportion of failures, rate of count recovery, and adverse events. We identified 28 articles within 3 broad strategies. Using a cyclophosphamide with growth factor strategy (10 articles), CD34+ cell yield is improved by addition of molgramostim to cyclophosphamide (1.4 vs 0.5 x 10(6)/kg; P = .0165), addition of cyclophosphamide to filgrastim (7.2 vs 2.5 x 10(6)/kg; P = .004), and addition of ancestim to cyclophosphamide and filgrastim (12.4 vs 8.3 x 10(6)/kg; P = .007). Within a growth factor-based strategy (6 articles), addition of plerixafor improves CD34+ cell yield over filgrastim alone in multiple myeloma (MM; 11.0 vs 6.2 x 10(6)/kg; P < .001) and non-Hodgkin lymphoma (5.69 vs 1.98 x 10(6)/kg; P < .01). With combination or noncyclophosphamide-based chemotherapy (12 articles), higher-dose filgrastim (8.2 vs 4.7 x 10(6)/kg for 16 vs 8/mcg/kg daily of filgrastim, respectively; P < .0001) and addition of rituximab to etoposide and filgrastim (9.9 vs 5.6 x 10(6)/kg; P = .021) improve CD34+ cell yield. Growth factor alone after chemotherapy, ancestim, or plerixafor provide adequate autologous HSC grafts for the majority of patients. Although some strategies result in higher CD34+ cell yield, this potentially comes at the expense of increased toxicity. As all strategies are reasonable, programmatic, and patient-specific considerations must inform the approach to autologous graft mobilization. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.