Tricot G, Jagannath S, Vesole D, Nelson J, Tindle S, Miller L, Cheson B, Crowley J, Barlogie B
Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock 72205.
Blood. 1995 Jan 15;85(2):588-96.
Transfusion of autologous peripheral blood stem cells (PBSCs) of good quality ensures fast hematopoietic engraftment after myeloablative therapy with a decrease in procedure-related morbidity and mortality. We have analyzed variables influencing the kinetics of engraftment, and therefore reflecting the quality of PBSC collections, in 225 patients with newly diagnosed or refractory multiple myeloma (MM) who received an autotransplant in support of high dose melphalan (200 mg/m2); 132 of these patients also completed a second transplant. All PBSCs were collected before the first transplant after high-dose cyclophosphamide (6 g/m2) and hematopoietic growth factors, mainly granulocyte-macrophage colony-stimulating factor. PBSCs were administered either alone (91 patients) or with bone marrow (134 patients). A highly significant correlation was observed between the number of CD34+ cells per kilogram infused and prompt recovery of both granulocytes (P = .0001) and platelets (P = .0001). After correction for the proportion of patients with > or = 2 x 10(6)/kg CD34 PBSCs infused and with < or = 12 months of prior therapy, no difference in engraftment kinetics was seen between patients receiving PBSCs only and those also receiving bone marrow. Exposure to chemotherapy, even to < or = 6 months of alkylating agents, significantly delayed hematopoietic recovery posttransplantation. The threshold dose of CD34 cells necessary for prompt engraftment was > or = 2.0 x 10(6)/kg for patients with < or = 24 months of chemotherapy before the first transplant, whereas greater than 5 x 10(6)/kg CD34 cells were required to assure rapid recovery also in those with longer exposure. Such quantities, easily collected in the large majority of patients with shorter exposure (91%), were obtained in only 28% of patients with more than 24 months of prior chemotherapy. Rapid platelet recovery within a narrow range of time (before day 14) was almost invariably seen (94%) when greater than 5 x 10(6)/kg CD34 cells were infused, irrespective of the duration of prior therapy, whereas the range widened progressively when less CD34 cells were infused. In the absence of CD34 measurements, fast recovery of platelets to greater than 50 x 10(9)/L within 14 days after high-dose cyclophosphamide and < or = 12 months of prior chemotherapy were the best predictors of early engraftment. Prudent use of stem cell-damaging agents, such as melphalan and nitrosoureas, is recommended in MM patients who might be candidates for autotransplantation. Alternatively, PBSCs should be collected early after diagnosis.
输注高质量的自体外周血干细胞（PBSCs）可确保在清髓性治疗后快速造血植入，同时降低与操作相关的发病率和死亡率。我们分析了225例新诊断或难治性多发性骨髓瘤（MM）患者的影响植入动力学的变量，这些患者接受自体移植以支持大剂量美法仑（200mg/m²）治疗；其中132例患者还完成了第二次移植。所有PBSCs均在首次移植前，于大剂量环磷酰胺（6g/m²）和造血生长因子（主要是粒细胞-巨噬细胞集落刺激因子）治疗后采集。PBSCs单独输注（91例患者）或与骨髓一起输注（134例患者）。观察到每千克输注的CD34⁺细胞数量与粒细胞（P = 0.0001）和血小板（P = 0.0001）的快速恢复之间存在高度显著相关性。在校正输注≥2×10⁶/kg CD34 PBSCs且先前治疗时间≤12个月的患者比例后，仅接受PBSCs的患者与同时接受骨髓的患者在植入动力学上没有差异。接触化疗，即使是接触≤6个月的烷化剂，也会显著延迟移植后的造血恢复。对于首次移植前化疗时间≤24个月的患者，快速植入所需的CD34细胞阈值剂量≥2.0×10⁶/kg，而对于接触时间更长的患者，则需要超过5×10⁶/kg CD34细胞以确保快速恢复。在大多数接触时间较短的患者（91%）中容易采集到的这些数量，在先前化疗超过24个月的患者中只有28%能够获得。当输注超过5×10⁶/kg CD34细胞时，几乎总是（94%）在狭窄的时间范围内（第14天之前）出现快速血小板恢复，与先前治疗的持续时间无关，而当输注的CD34细胞较少时，恢复范围会逐渐扩大。在没有CD34测量的情况下，大剂量环磷酰胺后14天内血小板快速恢复至超过50×10⁹/L且先前化疗时间≤12个月是早期植入的最佳预测指标。建议在可能进行自体移植的MM患者中谨慎使用如美法仑和亚硝基脲等会损害干细胞的药物。或者，应在诊断后尽早采集PBSCs。
