Infusion reactions are common after high-dose carmustine in BEAM chemotherapy and are not reduced by lengthening the time of administration.

PURPOSE: Carmustine (BCNU) is used in the conditioning regimens BEAM and CBV for autologous stem cell transplantation. Carmustine-related infusion reactions, while not described in the BEAM literature, occurred in 95 % of patients who received CBV. The most common symptoms include flushing, facial pain, headache, and hypotension. These reactions have been attributed to the absolute ethanol that is used in the reconstitution process or alternatively by a direct effect of carmustine. It is currently recommended that carmustine 300 mg/m2 be infused over at least 100 min (3-5 mg/m2/min). Prior to October 2014, carmustine infusions were given over 90 min but were changed to 120 min based on the above recommendation. We compared the two infusion rates in patients receiving BEAM to see if lengthening the infusion decreased the frequency of reactions. METHODS: Overall, 100 patients received BCNU as part of BEAM or Zevalin BEAM and were equally divided between 90 and 120 min infusion times. The primary outcome was the incidence of infusion-related reactions which were graded based on CTCAE 4.03 descriptions of flushing and infusion-related reactions. We also evaluated the impact of premedication as well as the efficacy of medications used to treat infusion reactions. RESULTS: Between the years 2013-2016, there were 50 patients who received BCNU over 90 min and 50 patients over 120 min. There were no significant differences observed for diagnosis, age and gender between the two groups. Twenty-eight (56 %) in the 90-min and 26 (52 %) in the 120-min infusion intervals developed a reaction (p = 0.6882). Of the patients that developed a reaction, 19 patients (67 %) in the 90-min and all 26 patients (100 %) in the 120-min infusion were given premedications predominately acetaminophen, in addition to dexamethasone. Among reacting patients, 57 % of the 90-min and 65 % of the 120-min groups received additional intervention (p = 0.53). CONCLUSION: Infusion reactions during high-dose BCNU are common and are not clearly reduced by modestly extending the duration of infusion or giving premedications.

Autologous Stem Cell Mobilization in the Age of Plerixafor.

BACKGROUND: Autologous stem cell transplantation remains important in the treatment of myeloma and relapsed lymphoma. Plerixafor has been shown to significantly enhance stem cell mobilization but is very expensive. PATIENTS AND METHODS: We evaluated plerixafor use in the 3-year period after its approval in December 2008. RESULTS: A total of 277 patients with myeloma and lymphoma had stem cell mobilization; 97.5% were successfully mobilized, including 41.5% who received plerixafor. Plerixafor was generally used for rescue after suboptimal granulocyte-colony stimulating factor (G-CSF) mobilization ("just in time") or for remobilization after an unsuccessful attempt with chemotherapy plus G-CSF. In addition, 10% of patients received planned G-CSF plus plerixafor because of high risk factors for inadequate collection. Rescue plerixafor was more effective in patients with myeloma than lymphoma as after 1 dose of plerixafor; 85% versus 55% collected a minimum number of stem cells (2 × 10E6 CD34 cells/kg) for 1 transplant and 51% versus 15% collected > 5 × 10E6 CD34 cells/kg. After transplantation, there were no significant differences in engraftment as a consequence of plerixafor use. Among all patients, there were less platelet transfusions in patients provided ≥ 3.5 × 10E6 CD34(+) cells/kg. CONCLUSION: With the judicious use of plerixafor, nearly all patients can collect enough stem cells to proceed to transplantation. Further studies, including hematologic tolerance to posttransplantation therapy, are required to determine the cost-effectiveness of using plerixafor to convert adequate to more optimal mobilizers.

Late afternoon dosing of plerixafor for stem cell mobilization: a practical solution.

BACKGROUND: Plerixafor was recently approved for stem cell mobilization in patients who have non-Hodgkin lymphoma or multiple myeloma. However, the use of late evening (10 PM) injections is inconvenient for patients and requires an after-hours infrastructure that may not be readily available. PATIENTS AND METHODS: Based on an earlier study showing prolonged mobilization of stem cells in patients given plerixafor plus granulocyte colony-stimulating factor (G-CSF), we administered plerixafor at 5 PM and performed apheresis approximately 15 hours later. Plerixafor was administered primarily to patients who either had failed previous mobilization or were at risk for poor mobilization because of previous therapy, especially lenalidomide in patients who had multiple myeloma. RESULTS: Of 48 patients, including 24 with myeloma and 24 with lymphoma, 47 had enough stem cells collected (> 2 × 10E6 CD34+ cells/kg) to proceed to transplant, including all 13 patients who had failed previous chemotherapy plus G-CSF mobilization and 18 patients treated with four cycles or more of lenalidomide. The day +1 post-plerixafor increment in circulating CD34+ cells was greatest in patients who had the highest preplerixafor CD34 count; however, in patients with preplerixafor CD34+ cell counts < 10/µL (and who typically mobilize poorly), 83% of patients had enough stem cells collected to proceed to transplant. CONCLUSION: This study suggests that plerixafor is effective when given 15 hours before apheresis, even in a population at high risk for mobilization failure. A proposed cost-effective use of plerixafor is to administer it to patients who are inadequately mobilized with G-CSF alone or for salvage in patients who fail previous mobilization with chemotherapy plus G-CSF.