There were no drop outs

There were no drop outs. 7 AM and immediately pre-apheresis on day 5, for a total interval time of 17C18 hours post-plerixafor. Data was analyzed useing mixed model analysis of repeated measures and paired t-testing. Results Ten of the 11 subjects achieved a CD34+ product count of 2 106/kg with a single leukapheresis. All 10 had a pre-plerixafor PB CD34+ concentration of at least 10/uL. PB CD34+ concentrations were not different between 10C18 hours post-plerixafor (p0.8). In contrast, PB CD34+CD38? concentrations significantly increased from 10 to 18 hours post-plerixafor (p=0.03). Conclusions In MM and NHL patients with adequate pre-plerixafor CD34+ concentrations, leukapheresis initiated 14C18 hours after plerixafor/G-CSF mobilization may not impair adequate CD34+ collection and may increase more primitive CD34+CD38? collection. In this subset of patients, late afternoon dosing of plerixafor at 5 pm with initiation of next-day apheresis as late as 11 am appears feasible without loss of efficacy. strong class=”kwd-title” Keywords: plerixafor, hematopoietic stem cell mobilization, pharmacodynamics, Antigens, CD34, Antigens, CD38, Granulocyte-colony stimulating factor Introduction Plerixafor (Mozobil, Genzyme, Cambridge, MA) is approved for hematopoietic progenitor cell (HPC) mobilization into peripheral blood (PB) in combination with granulocyte colony stimulating factor (G-CSF) in patients with multiple myeloma (MM) and non-Hodgkins lymphoma (NHL) (1, 2). Plerixafor reversibly inhibits binding of stromal cell-derived factor-1 (SDF-1) to its cognate chemokine receptor CXCR4. Dosing is approved at approximately 11 hours (hr) prior to apheresis initiation, preferably in a health care setting due to the risk of an adverse hypotensive reaction. Since apheresis facilities typically open at 8C9 AM, the approved 11 hr interval requires plerixafor dosing between 9C10 pm, impractical unless the patient self-administers the drug. Prior studies suggest that PB CD34+ concentration ([CD34+]) may be maintained. Pharmacodynamic studies in normal volunteers given plerixafor alone (3), and MM and NHL patients given G-CSF and plerixafor (4, 5), generally show increasing PB [CD34+] out to 10C11 hr after plerixafor. A retrospective study of 48 primarily MM and NHL patients, collected 15 Tiplaxtinin (PAI-039) hr after 5pm plerixafor, found that 47 patients reached 2 106 CD34+ cells/kg with a median 2 days of apheresis (6). Recently, 22 of 31 MM patients prospectively collected ~17 Tiplaxtinin (PAI-039) hr after plerixafor reached 10 106 CD34+ cells/kg with 1 large volume leukapheresis (7). In 3 normal volunteers given G-CSF and plerixafor, the peak PB [CD34+] was at 14 hr but was sustained until Rabbit polyclonal to NFKB3 18 hours after dosing (8). The 18 hr peak was 3 times that seen with G-CSF alone, comparable to a 2.9 fold peak over G-CSF alone at 6 hr post-plerixafor (9) and a 2.5 fold peak over G-CSF alone at 10 hr post-plerixafor (10). A prospective study of 13 known poor mobilizers, however, found that, in 4 patients who had PB [CD34+] followed out to 14C15 hr, the [CD34+] at that time was significantly decreased from the earlier peak [CD34+] (11). Studying, in the target population of MM and NHL patients, a total interval time of 17C18 hr post-plerixafor is important because, in practical terms, the actual leukapheresis may not be initiated until 10C11 AM. Furthermore, even if initiated earlier between 8C9 AM, a standard leukapheresis of 3 total blood volumes typically lasts 3 hr. Therefore, it is important to rule out a significant decrease in PB [CD34+] extending through this interval. Materials and Methods This was a single-center, prospective cohort IRB-approved study in 11 patients with NHL and MM who underwent HPC mobilization as part of standard care at Mount Sinai Medical Center from March 2010 to October 2011. Written and informed consent was obtained on all subjects. Patients were required to meet the same entry criteria specified in the initial studies that led to FDA approval, which notably excluded patients who had failed previous HPC collections or collection attempts (1, 2). Baseline PB [CD34+] before you start G-CSF was evaluated with two individually collected examples (Amount 1). Donors after that received once daily morning hours subcutaneous G-CSF (Neupogen, Amgen, Thousands of Oaks, CA) at 10 ug/kg for 5 times. Over the 4th time of G-CSF, subcutaneous plerixafor at 240 ug/kg was implemented at 5pm and sufferers were admitted right away towards the Clinical Analysis Center at Support Sinai. Instantly pre-plerixafor (5 pm on time 4), every following 2 hours until 7 AM of time 5, and between 10C11 AM (the initiation of apheresis), 4 ml of PB was attracted through a 20-measure angiocath mounted on a medlock for Compact disc34+ and Compact disc34+Compact disc38? enumeration. Examples were attracted after discard of 2 mL of PB, and work Tiplaxtinin (PAI-039) using regular technique (Stem-Kit, Compact disc38 Ab, Beckman Coulter, Brea, CA) in the scientific flow cytometry lab. Leukapheresis was performed if the 7 am peripheral bloodstream Compact disc34+ focus was at least 10/uL. Around 3 total bloodstream amounts using the producers Mononuclear Cell method from the COBE.