Stiff Patrick, Micallef Ivana, McCarthy Philip, Magalhaes-Silverman Margarida, Weisdorf Daniel, Territo Mary, Badel Karin, Calandra Gary
BMT Program, Loyola University Stritch School of Medicine, Maywood, Illinois, USA.
Biol Blood Marrow Transplant. 2009 Feb;15(2):249-56. doi: 10.1016/j.bbmt.2008.11.028.
We investigated the efficacy and toxicity of combining granulocyte-colony stimulating factor (G-CSF) at standard doses with plerixafor, a CXCR4 inhibitor, to mobilize stem cells in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Patients with NHL and MM underwent mobilization with G-CSF (10 microg/kg/day) for up to 9 days and plerixafor (240 microg/kg/day), which started on the evening of day 4. Apheresis began on day 5 and continued daily until either >or= 5 x 10(6) CD34/kg were collected or to a maximum of 5 aphereses. Toxicities, increase in circulating CD34 cells/microL before and after the first dose of plerixafor, percentage of patients collecting >or= 5 x 10(6) CD34/kg, total CD34 cells/kg collected, engraftment, and exploratory efficacy analyses in heavily pretreated patients were examined. Six sites enrolled 49 patients (NHL, 23; MM, 26). All completed mobilization and 47 of 49 (96%) underwent transplant. Circulating CD34 cells/microL increased by 2.5-fold (1.3-6.0-fold) after the first plerixafor dose. The median CD34 cells/kg collected was 5.9 x 10(6) (1.5-22.5) in 2 (1-5) days of aphereses. Median days to neutrophil and platelet engraftment were 11 (8-16) and 14.5 (7-39) days, respectively. Adverse events primarily were mild nausea and diarrhea (n=24). Twenty-eight (57%) were identified as heavily pretreated patients. Their median fold increase in circulating CD34 cells/microL was 2.5 (1.4-5.0) after plerixafor, similar to minimally pretreated patients. Plerixafor and G-CSF increased circulating CD34 cells/microL and led to the adequate collection of stem cells for autotransplant in 96% of the patients. This combination may have particular value in heavily pretreated patients.
我们研究了标准剂量的粒细胞集落刺激因子（G-CSF）与CXCR4抑制剂普乐沙福联合使用，动员非霍奇金淋巴瘤（NHL）和多发性骨髓瘤（MM）患者干细胞的疗效和毒性。NHL和MM患者接受G-CSF（10微克/千克/天）动员，持续时间长达9天，普乐沙福（240微克/千克/天）于第4天晚上开始使用。第5天开始进行单采，每天持续进行，直至采集到≥5×10⁶个CD34⁺细胞/千克，或最多进行5次单采。研究了毒性、首次使用普乐沙福前后循环CD34⁺细胞/微升的增加情况、采集到≥5×10⁶个CD34⁺细胞/千克的患者百分比、采集到的总CD34⁺细胞/千克、植入情况以及对预处理严重患者的探索性疗效分析。6个研究点招募了49例患者（NHL 23例；MM 26例）。所有患者均完成动员，49例中有47例（96%）接受了移植。首次使用普乐沙福后，循环CD34⁺细胞/微升增加了2.5倍（1.3 - 6.0倍）。在2（1 - 5）天的单采过程中，采集到的CD34⁺细胞/千克中位数为5.9×10⁶（1.5 - 22.5）。中性粒细胞和血小板植入的中位天数分别为11（8 - 16）天和14.5（7 - 39）天。不良事件主要为轻度恶心和腹泻（n = 24）。28例（57%）被确定为预处理严重的患者。普乐沙福治疗后，他们循环CD34⁺细胞/微升的中位增加倍数为2.5（1.4 - 5.0），与预处理轻微的患者相似。普乐沙福和G-CSF增加了循环CD34⁺细胞/微升，并使96%的患者能够充分采集到用于自体移植的干细胞。这种联合用药在预处理严重的患者中可能具有特殊价值。
