Konopleva Marina, Benton Christopher B, Thall Peter F, Zeng Zhihong, Shpall Elizabeth, Ciurea Stefan, Kebriaei Partow, Alousi Amin, Popat Uday, Anderlini Paolo, Nieto Yago, Parmar Simrit, Qiao Wei, Chen Julianne, Rondon Gabriela, McMullin Becky, Wang Rui-Yu, Lu Hongbo, Schober Wendy, Woodworth Glenda, Gulbis Alison, Cool Rita, Andreeff Michael, Champlin Richard
Department of Stem Cell Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Bone Marrow Transplant. 2015 Jul;50(7):939-946. doi: 10.1038/bmt.2015.58. Epub 2015 Apr 13.
We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.
我们假设，在异基因干细胞移植（allo-SCT）的预处理化疗期间，使用粒细胞集落刺激因子（G-CSF）联合CXCR4特异性抑制剂普乐沙福破坏基质-白血病细胞间的相互作用，可能会促进白血病细胞从其龛位释放，并增强肿瘤清除效果。在一项1/2期研究中，我们对45例急性髓系白血病（AML）/骨髓增生异常综合征（MDS）/慢性髓系白血病（CML）患者（34例AML、7例MDS和4例CML）采用G-CSF（从第-9天开始，每日10μg/kg，共6天）加普乐沙福（从第-7天开始，每日剂量分别为0、80、160或240μg/kg，共4天），同时采用白消安-氟达拉滨（Bu-Flu）预处理方案。在1期研究中，我们确定在此情况下G-CSF加普乐沙福是安全的。我们通过对细胞遗传学和疾病状态进行分层以校正偏倚，将AML/MDS研究患者（n = 40）的临床疗效和结局与164例来自历史数据集、在allo-SCT前仅接受Bu-Flu治疗的患者进行了比较。研究患者的髓系嵌合率增加，移植物抗宿主病（GvHD）发生率降低。无复发生存率或总生存率无显著差异。G-CSF加普乐沙福的联合用药增加了循环白细胞、CD34+细胞和CXCR4+细胞，并优先动员了荧光原位杂交（FISH）阳性的白血病细胞。
