Nademanee A, Sniecinski I, Schmidt G M, Dagis A C, O'Donnell M R, Snyder D S, Parker P M, Stein A S, Smith E P, Molina A
Department of Hematology/Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010.
J Clin Oncol. 1994 Oct;12(10):2176-86. doi: 10.1200/JCO.1994.12.10.2176.
To evaluate (1) the effect of granulocyte colony-stimulating factor (G-CSF) on peripheral-blood stem-cell (PBSC) mobilization; (2) the rate of hematopoietic recovery after G-CSF-mobilized PBSC transplantation; and (3) the outcome of high-dose myeloablative therapy and PBSC transplantation in patients with relapsed or refractory lymphoma.
Ninety-five patients with lymphoma underwent high-dose therapy followed by PBSC transplant in three sequentially treated cohorts of patients in a nonrandomized study. The first 30 patients received nonmobilized PBSCs (unprimed) without G-CSF after transplant, the next 26 patients received PBSC that were mobilized with G-CSF 5 micrograms/kg/d (primed-5) plus G-CSF after transplant, and the last 39 patients received PBSC mobilized by G-CSF 10 micrograms/kg/d (primed-10) plus G-CSF after transplant. The conditioning regimen consisted of fractionated total-body irradiation (FTBI) 12 Gy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg. Patients with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI.
The use of G-CSF-mobilized PBSCs in combination with G-CSF posttransplant resulted in a significantly accelerated time to recovery of both granulocyte and platelet when compared with the unprimed group. The median number of days to an absolute granulocyte count (ANC) of greater than 0.5 x 10(9)/L was 10 days for G-CSF primed versus 20 days for the unprimed (P = .0001). The median days to platelet transfusion independence was 16 and 31 days (P = .0001) for the G-CSF primed and unprimed, respectively. There were also significant reductions in the number of platelet (P = .02) and RBC transfusions (P = .006) for the G-CSF primed. Multivariate analysis of prognostic factors identified CD34+ cell dose as the only additional factor predicting engraftment. Sixty-nine patients are alive at a median follow-up of 15.9 months (range, 7.4 to 63.7). The cumulative probability of 2-year disease-free survival is 59% (95% confidence interval [CI], 36% to 79%) and 39% (95% CI 25% to 55%) for patients with Hodgkin's disease and non-Hodgkin's lymphoma, respectively.
The use of G-CSF-mobilized PBSC after high-dose myeloablative therapy resulted in a rapid, complete, and sustained hematopoietic recovery. Disease-free survival over 2 years can be achieved in some patients with relapsed lymphoma after high-dose therapy and PBSC transplantation. However, longer follow-up is required to confirm the curability of this approach.
评估(1)粒细胞集落刺激因子(G-CSF)对外周血干细胞(PBSC)动员的影响;(2)G-CSF动员的PBSC移植后造血恢复的速率;以及(3)复发或难治性淋巴瘤患者接受大剂量清髓性治疗和PBSC移植的结果。
95例淋巴瘤患者在一项非随机研究中按顺序接受了三个队列的大剂量治疗,随后进行PBSC移植。前30例患者移植后接受未动员的PBSC(未预处理)且未使用G-CSF,接下来的26例患者移植后接受用5微克/千克/天的G-CSF动员的PBSC(预处理-5)加G-CSF,最后39例患者移植后接受用10微克/千克/天的G-CSF动员的PBSC(预处理-10)加G-CSF。预处理方案包括12 Gy的分次全身照射(FTBI)联合60毫克/千克的依托泊苷和100毫克/千克的环磷酰胺。既往接受过放疗的患者用450毫克/平方米的卡莫司汀(BCNU)代替FTBI。
与未预处理组相比,移植后使用G-CSF动员的PBSC联合G-CSF可显著加速粒细胞和血小板的恢复时间。G-CSF预处理组中性粒细胞绝对计数(ANC)大于0.5×10⁹/L的中位天数为10天,未预处理组为20天(P = 0.0001)。G-CSF预处理组和未预处理组血小板输注独立的中位天数分别为16天和31天(P = 0.0001)。G-CSF预处理组的血小板(P = 0.02)和红细胞输注次数(P = 0.006)也显著减少。预后因素的多变量分析确定CD34⁺细胞剂量是预测植入的唯一其他因素。69例患者在中位随访15.9个月(范围7.4至63.7个月)时存活。霍奇金病和非霍奇金淋巴瘤患者2年无病生存的累积概率分别为59%(95%置信区间[CI],36%至79%)和39%(95%CI 25%至55%)。
大剂量清髓性治疗后使用G-CSF动员的PBSC可导致快速、完全且持续的造血恢复。一些复发淋巴瘤患者在接受大剂量治疗和PBSC移植后可实现超过2年的无病生存。然而,需要更长时间的随访来证实这种方法的可治愈性。