Mirgh Sumeet, Bagal Bhausaheb, Punatar Sachin, Gokarn Anant, Jindal Nishant, Chichra Akanksha, Nayak Lingaraj, Hiregoudar Sumathi, Poojary Minal, Saha Suryatapa, Parab Sarika, Ojha Shashank, Tembhare Prashant, Patkar Nikhil, Rajpal Sweta, Chatterjee Gaurav, Mathew Libin, Subramanian Papagudi, Khattry Navin
BMT Unit, Department of Medical Oncology, Tata Memorial Centre, ACTREC, Navi Mumbai, India.
Homi Bhabha National Institute (HBNI), Mumbai, India.
Cancer Med. 2025 Jul;14(14):e71068. doi: 10.1002/cam4.71068.
Stem-cell mobilization in multiple myeloma is usually done with G-CSF with or without Cyclophosphamide (Cy) based chemotherapy/Plerixafor. Pre-clinical data suggest the role of proteasome inhibitors in mobilization. We previously reported that Bortezomib (Bort) when added to a Cy-based regimen had a better stem-cell yield. Consequent to favorable results with Bort + Cy-G-CSF, we used Bortezomib with G-CSF too. Hence, four different mobilization regimens were used-Bort + G-CSF (Group-1); G-CSF + Plerixafor (Group-2); Bort - Cy-G-CSF (Group-3); Cy + G-CSF (Group-4). We report here our 15-year retrospective analysis of these 4 mobilization regimens.
Primary objective was to determine proportion of patients with CD34 dose ≥ 5 × 10/kg in first apheresis in various groups. Secondary objectives were to determine median CD34 dose (×10/kg) in first apheresis, total median CD34 dose (×10/kg) of all harvests and frequency of mobilization failure. Mobilization failure was defined as total CD34 dose of < 2 × 10/kg or abandoned harvest attempt at physician's discretion after anticipating a poor collection.
All consecutive patients with MM aged 18-65 years who underwent stem-cell mobilization from September 2007-December 2022 were included. In an intention-to-treat analysis, a total 200 patients with 205 mobilization attempts were analysed. The median age of the cohort was 48 years. The percentage of patients who collected ≥ 5 × 10 CD34 cells/kg in the first apheresis was 26%, 53%, 69%, and 63% in Groups 1-4, respectively (p = 0.0001). The median CD34 yield in the first harvest (×10/kg) was 3.62, 5.20, 6.04, and 6.05 in Groups 1-4, respectively (p = 0.00004). The median total stem-cell dose collected (×10/kg) was 5.73, 6.17, 9.14, and 8.23 in Groups 1-4, respectively (p < 0.00001). Mobilization failure rates were 7%, 3%, 0%, and 2%, respectively (p = NS).
Cyclophosphamide-based chemo-mobilization regimens with or without Bortezomib have the advantage of higher total stem-cell yield, while they are equivalent to G-CSF + Plerixafor for harvest in a single apheresis. The addition of Bortezomib to Cyclophosphamide may help to increase stem cell yield.
多发性骨髓瘤中的干细胞动员通常使用粒细胞集落刺激因子(G-CSF),联合或不联合基于环磷酰胺(Cy)的化疗/普乐沙福。临床前数据表明蛋白酶体抑制剂在动员中的作用。我们之前报道过,硼替佐米(Bort)添加到基于Cy的方案中时,干细胞产量更高。鉴于硼替佐米+Cy-G-CSF取得了良好结果,我们也将硼替佐米与G-CSF联合使用。因此,使用了四种不同的动员方案——硼替佐米+G-CSF(第1组);G-CSF+普乐沙福(第2组);硼替佐米-Cy-G-CSF(第3组);Cy+G-CSF(第4组)。我们在此报告对这四种动员方案的15年回顾性分析。
主要目的是确定各小组首次单采中CD34剂量≥5×10⁶/kg的患者比例。次要目的是确定首次单采中的CD34剂量中位数(×10⁶/kg)、所有采集的CD34剂量总中位数(×10⁶/kg)以及动员失败的频率。动员失败定义为总CD34剂量<2×10⁶/kg,或在预计采集效果不佳后,医生酌情决定放弃采集尝试。
纳入了2007年9月至2022年12月期间接受干细胞动员的所有18至65岁的连续性骨髓瘤患者。在意向性分析中,共分析了200例患者的205次动员尝试。该队列的中位年龄为48岁。第1至4组首次单采中采集到≥5×10⁶个CD34细胞/kg的患者百分比分别为26%、53%、69%和63%(p = 0.0001)。第1至4组首次采集的CD34产量中位数(×10⁶/kg)分别为3.62)、5.20、6.04和6.05(p = 0.00004)。第1至4组采集的干细胞总剂量中位数(×10⁶/kg)分别为5.73、6.17、9.14和8.23(p < 0.00001)。动员失败率分别为7%、3%、0%和2%(p = 无统计学意义)。
含或不含硼替佐米的基于环磷酰胺的化学动员方案具有干细胞总产量更高的优势,而在单次单采收获方面与G-CSF+普乐沙福相当。在环磷酰胺中添加硼替佐米可能有助于提高干细胞产量。