Schiller G, Vescio R, Freytes C, Spitzer G, Sahebi F, Lee M, Wu C H, Cao J, Lee J C, Hong C H
Department of Medicine, UCLA School of Medicine 90024-1678, USA.
Blood. 1995 Jul 1;86(1):390-7.
A major potential problem of autologous transplantation in the treatment of advanced malignancy is the infusion of tumor cells. A multi-institutional study of purified CD34-selected peripheral blood progenitor cell (PBPC) transplantation was conducted in 37 patients with advanced multiple myeloma receiving myeloablative chemotherapy. Fourteen days after intermediate-dose cyclophosphamide, prednisone, and granulocyte colony-stimulating factor (G-CSF), a median of 3 (range, 2 to 5) 10-L leukaphereses yielded 9.8 x 10(8)/kg (range, 3.7 to 28.3) mononuclear cells. The adsorbed (column-bound) fraction contained 5.9 x 10(6) cells/kg (range, 1.6 to 25.5) with 4.65 x 10(6) CD34 cells/kg (range, 1.2 to 23.3). Using Poisson distribution analysis of positive polymerase chain reactions with patient-specific complementarity-determining region 1 (CDR1) and CDR3 Ig-gene primers, tumor was detected in leukapheresis products from 8 to 14 unselected patients and ranged from 1.13 x 10(4) to 2.14 x 10(6) malignant cells/kg. After CD34 selection, residual tumor was detected in only three patients' products. Overall, a greater than 2.7- to 4.5-log reduction in contaminating multiple myeloma cells was achieved. CD34 PBPCs were infused 1 day after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg), and granulocyte-macrophage colony-stimulating factor was used until hematologic recovery. The median time to both neutrophil and platelet recovery was 12 days (range, 11 to 16 days and 9 to 52 days, respectively). The median number of erythrocyte and platelet transfusions was 7 (range, 2 to 37) and 3 (range, 0 to 85), respectively. Patients receiving fewer than 2 x 10(6) CD34 cells/kg had significantly prolonged neutropenia, thrombocytopenia, and an increased red blood cell and platelet transfusion requirement. Thus, CD34 selection of PBPCs markedly reduces tumor contamination in multiple myeloma and provides effective hematopoietic support for patients receiving myeloablative therapy.
自体移植治疗晚期恶性肿瘤的一个主要潜在问题是肿瘤细胞的输注。对37例接受清髓性化疗的晚期多发性骨髓瘤患者进行了一项关于纯化的CD34选择外周血祖细胞(PBPC)移植的多机构研究。在给予中剂量环磷酰胺、泼尼松和粒细胞集落刺激因子(G-CSF)14天后,中位3次(范围2至5次)10-L白细胞分离术采集到9.8×10⁸/kg(范围3.7至28.3)个单核细胞。吸附(柱结合)部分含有5.9×10⁶个细胞/kg(范围1.6至25.5),其中有4.65×10⁶个CD34细胞/kg(范围1.2至23.3)。使用患者特异性互补决定区1(CDR1)和CDR3 Ig基因引物进行阳性聚合酶链反应的泊松分布分析,在8至14例未进行选择的患者的白细胞分离产物中检测到肿瘤,恶性细胞数量范围为1.13×10⁴至2.14×10⁶个/kg。经过CD34选择后,仅在3例患者的产物中检测到残留肿瘤。总体而言,多发性骨髓瘤污染细胞减少了超过2.7至4.5个对数级。在白消安(14mg/kg)和环磷酰胺(120mg/kg)治疗1天后输注CD34 PBPC,并使用粒细胞巨噬细胞集落刺激因子直至血液学恢复。中性粒细胞和血小板恢复的中位时间均为12天(范围分别为11至16天和9至52天)。红细胞和血小板输注的中位数分别为7次(范围2至37次)和3次(范围0至85次)。接受低于2×10⁶个CD34细胞/kg的患者中性粒细胞减少、血小板减少时间显著延长,红细胞和血小板输注需求增加。因此,PBPC的CD34选择显著减少了多发性骨髓瘤中的肿瘤污染,并为接受清髓性治疗的患者提供了有效的造血支持。