AUTOLOGOUS PROGENITOR-CELL TRANSPLANTATION - PRIOR EXPOSURE TO STEM CELL-TOXIC DRUGS DETERMINES YIELD AND ENGRAFTMENT OF PERIPHERAL-BLOOD PROGENITOR-CELL BUT NOT OF BONE-MARROW GRAFTS
AUTOLOGOUS PROGENITOR-CELL TRANSPLANTATION - PRIOR EXPOSURE TO STEM CELL-TOXIC DRUGS DETERMINES YIELD AND ENGRAFTMENT OF PERIPHERAL-BLOOD PROGENITOR-CELL BUT NOT OF BONE-MARROW GRAFTS
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DOI：
10.1182/blood.v86.10.3970.bloodjournal86103970
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发表时间：
1995-11-15
期刊：
影响因子：
20.3
通讯作者：
SCHMITZ, N
中科院分区：
文献类型：
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作者：
DREGER, P;KLOSS, M;SCHMITZ, N
具有干细胞毒性潜力的药物经常用于霍奇金病（HD）和高级别非霍奇金淋巴瘤（NHL）的挽救治疗。由于许多复发性或难治性淋巴瘤患者都是自体祖细胞移植的候选者，因此必须考虑挽救性化疗对祖细胞可能产生的毒性作用。在一项回顾性研究中，我们分析了含有干细胞毒性药物 BCNU 和美法仑 (Dexa-BEAM) 的挽救方案对随后收获的骨髓 (BM) 和外周血来源的祖细胞移植物 (PBPC) 的影响，并将其与其他因素进行了比较。祖细胞收集自 96 名 HD 或高度 NHL 患者。高剂量化疗后，79 个移植物被回输（35 个 PBPC 和 44 个 BM）。与自体骨髓移植的患者相比，PBPC 受者的造血恢复速度显着加快。对于 PBPC，Dexa-BEAM 循环次数（小于或等于 1 v >1）是影响集落形成单位粒细胞巨噬细胞 (CFU-GM) 产量（66 v 6.8 x 10(4)/kg，P = .0001）、CD34(+) 细胞产量（6.6 v 1.6 x 10(6)/kg，P = .0001)，中性粒细胞恢复至 >0.5 x 10(9)/L（9 vs. 11 天，P = .0086），血小板恢复至 >20 x 10(9)/L（10 vs 15.5 天，P = .0002），以及移植后+100 天的血小板计数（190 v 107 x 10(9)/L，P = .031) 使用单变量分析。既往放疗与显着降低的 CFU-GM 和 CD34(+) 细胞产量相关，但对植入没有影响。患者年龄、患者性别、疾病活动度或 Dexa-BEAM 以外的化疗对预后没有任何影响。多变量分析证实，Dexa-BEAM 化疗是对 CFU-GM 产量 (P < .0001)、CD34(+) 细胞产量 (P < .0001) 和血小板植入 (P < .0001) 产生不利影响的首要因素。先前的 Dexa-BEAM 化疗或任何其他测试变量并未对 BM 移植物产生显着影响。然而，使用涉及移植物类型（PBPC 或 BM）与所研究的解释变量之间的相互作用项的联合回归模型，并未确定有利于使用 BM 代替 PBPC 的预后因素。我们的结论是，与之前的放疗或其他化疗相比，暴露于含有干细胞毒性药物（例如 BCNU 和美法仑）的挽救方案是对 PBPC 移植物的产量和性能产生不利影响的关键因素。骨髓祖细胞似乎对干细胞毒性化疗不太敏感，因此应在涉及干细胞毒性药物的重复挽救化疗疗程之前收获 PBPC，以保持 PBPC 与 BM 相比有利的再增殖动力学。 (C) 1995 年，美国血液学会。
Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles (less than or equal to 1 v >1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34(+) cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to >0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to >20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34(+) cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34(+) cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy, PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM. (C) 1995 by The American Society of Hematology.