Weisdorf D, Miller J, Verfaillie C, Burns L, Wagner J, Blazar B, Davies S, Miller W, Hannan P, Steinbuch M, Ramsay N, McGlave P
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Biol Blood Marrow Transplant. 1997 Oct;3(4):217-23.
Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic recovery and short hospital stay compared with cytokine-primed PBSC. Using primed BMSC, no difference in malignant relapse or relapse-free survival was observed. These findings suggest that despite widespread use of PBSC for transplantation, BMSC, when collected following hematopoietically stimulating cytokines, may remain a satisfactory source of stem cells for autologous transplantation. G-CSF and GM-CSF are both effective in priming autologous PBSC or BMSC for collection.
自体移植用于非霍奇金淋巴瘤和霍奇金病，已被广泛用作高危或复发肿瘤患者的标准治疗方法。外周血干细胞（PBSC）采集几乎已完全取代骨髓干细胞（BMSC）采集，因为人们认为PBSC具有植入更快、接种物中肿瘤污染更少以及治疗后生存率更高的优势。然而，PBSC的优势可能源于用于PBSC动员的造血刺激细胞因子。因此，我们对粒细胞巨噬细胞集落刺激因子（GM-CSF）与粒细胞集落刺激因子（G-CSF）进行了随机对照试验，这两种因子分别用于在采集前预处理BMSC或PBSC，以供自体移植使用。62例接受非霍奇金淋巴瘤（n = 51）或霍奇金病（n = 11）移植的患者（31例PBSC；31例BMSC）接受了治疗。所有患者均接受6天随机分配的细胞因子治疗。形态学缓解且骨髓细胞正常的患者接受BMSC采集，而骨髓细胞减少或存在微小骨髓肿瘤浸润的患者则采集PBSC。所有组中性粒细胞恢复情况相似（中位时间14天；范围10 - 23天），不过有2例使用GM-CSF预处理PBSC的患者中性粒细胞恢复延迟（p = 0.01）。用GM-CSF动员的BMSC或用G-CSF动员的PBSC后，红细胞和血小板恢复明显更快。这种更快的血液学恢复也导致了更早出院。然而，在多变量分析中，干细胞来源以及随机分配的G-CSF与GM-CSF均与更早的多系血液学恢复或更短的住院时间无独立相关性。无复发生存率不受分配的干细胞来源或随机分配的预处理细胞因子的独立影响，不过分配到PBSC组的患者恶性复发更频繁（复发相对风险3.15，p = 0.03）。这些数据表明，经细胞因子预处理后采集的BMSC与经细胞因子预处理的PBSC相比，血液学恢复同样迅速，住院时间同样短。使用预处理的BMSC，未观察到恶性复发或无复发生存率的差异。这些发现表明，尽管PBSC在移植中广泛应用，但经造血刺激细胞因子预处理后采集的BMSC可能仍是自体移植令人满意的干细胞来源。G-CSF和GM-CSF在预处理自体PBSC或BMSC以供采集方面均有效。
