Bentley S A, Brecher M E, Powell E, Serody J S, Wiley J M, Shea T C
Department of Pathology, University of North Carolina, Chapel Hill 27514, USA.
Bone Marrow Transplant. 1997 Mar;19(6):557-63. doi: 10.1038/sj.bmt.1700717.
We infused peripheral blood stem cells (PBSC) into 51 patients with various malignant disorders, after myeloablative conditioning. Twenty-four patients also received autologous bone marrow (PBSC + BM). In a multivariate analysis, the only statistically significant predictors of neutrophil engraftment were log-dose CFU-GM (P < 0.001) and the number of prior chemotherapy regimens (P = 0.004). The factors predicting RBC and platelet engraftment were log-dose CFU-GM (P = 0.002), PBSC + BM infusion (P = 0.007) and the absence of neoplastic bone marrow involvement (P = 0.009). Seven patients remained platelet and/or red cell transfusion-dependent for 100 days or more post-transplant after good neutrophil recovery. Six of these seven long-term engraftment failures, as well as five additional patients, received < 10(5) CFU-GM/kg. Of the 11 patients who received < 10(5) CFU-GM/kg (low-dose patients), seven were PBSC recipients, of whom six were long-term engraftment failures. In contrast, there were no long-term engraftment failures among the four low-dose autologous marrow recipients. This difference in long-term engraftment failure rate was significant (P = 0.015). The low-dose PBSC patients all had a diagnosis of lymphoma with bone marrow involvement. The low-dose PBSC + BM group was more heterogeneous, but no patient had malignant involvement of the marrow. The low-dose PBSC patients had also received significantly more prior chemotherapy regimens than the low-dose PBSC + BM patients and a significantly higher proportion received total body irradiation (TBI) as part of their conditioning regimen. We conclude that marrow damage resulting from a combination of neoplastic infiltration, chemotherapy and TBI may result not only in low PBSC yields but also in an impaired capacity of the marrow microenvironment to support transplanted stem cells.
我们在进行清髓性预处理后，将外周血干细胞（PBSC）输注给51例患有各种恶性疾病的患者。24例患者还接受了自体骨髓（PBSC + BM）。在多变量分析中，中性粒细胞植入的唯一具有统计学意义的预测因素是对数剂量的CFU - GM（P < 0.001）和既往化疗方案的数量（P = 0.004）。预测红细胞和血小板植入的因素是对数剂量的CFU - GM（P = 0.002）、PBSC + BM输注（P = 0.007）以及无肿瘤性骨髓受累（P = 0.009）。7例患者在中性粒细胞良好恢复后，移植后100天或更长时间仍依赖血小板和/或红细胞输血。这7例长期植入失败患者中的6例，以及另外5例患者，接受的CFU - GM/kg < 10⁵ 。在接受CFU - GM/kg < 10⁵ 的11例患者（低剂量患者）中，7例是PBSC接受者，其中6例是长期植入失败患者。相比之下，4例低剂量自体骨髓接受者中没有长期植入失败患者。长期植入失败率的这种差异具有统计学意义（P = 0.015）。低剂量PBSC患者均诊断为淋巴瘤伴骨髓受累。低剂量PBSC + BM组更为异质，但没有患者有骨髓恶性受累。低剂量PBSC患者既往接受的化疗方案也明显多于低剂量PBSC + BM患者，并且作为预处理方案的一部分接受全身照射（TBI）的比例明显更高。我们得出结论，肿瘤浸润、化疗和TBI共同导致的骨髓损伤不仅可能导致PBSC产量低，而且可能导致骨髓微环境支持移植干细胞的能力受损。
