Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Japan.
Ann Oncol. 2011 Aug;22(8):1865-71. doi: 10.1093/annonc/mdq673. Epub 2011 Feb 2.
Because of the less graft-facilitating effect by bone marrow (BM), we need to assess a dosage of conditioning more accurately particularly in combination with reduced-intensity conditioning. Thus we examined that modified continual reassessment method (mCRM) is applicable for deciding appropriate conditioning of allogeneic BM transplantation.
The conditioning regimen consisted of i.v. fludarabine (125 mg/m2) plus an examination dose of i.v. melphalan. The primary endpoint was a donor-type T-cell chimerism at day 28 with successful engraftment defined as >90% donor cells. Five patients per dose level were planned to be accrued and chimerism data were used to determine the next dose.
Seventeen patients were enrolled at doses between 130 and 160 mg/m2. The dose was changed from 160 to 130 mg/m(2) (second level) after five full-donor chimerisms. With one patient of 0% chimera in the second level, the dose was increased to 135 mg/m2 (third level). Following five full-donor chimerisms in the third level, the study was complete as projected.
mCRM was shown to be a relevant method for dose-finding of conditioning regimen. The melphalan dose of 135 mg/m2 was determined as the recommended phase II dose to induce initial full-donor chimerism.
由于骨髓（BM）的移植物促进作用较低，我们需要更准确地评估剂量，尤其是与低强度预处理相结合时。因此，我们研究了改良连续评估方法（mCRM）是否适用于确定异基因 BM 移植的适当预处理方案。
预处理方案包括静脉注射氟达拉滨（125mg/m2）加静脉注射美法仑的试验剂量。主要终点是在第 28 天出现供体 T 细胞嵌合体，成功植入定义为>90%供体细胞。计划在每个剂量水平上招募 5 名患者，并使用嵌合体数据来确定下一个剂量。
17 名患者在 130 至 160mg/m2 之间的剂量水平入组。在 5 名完全供体嵌合体后，剂量从 160 改为 130mg/m2（第二水平）。在第二水平中有 1 名患者嵌合体为 0%，剂量增加至 135mg/m2（第三水平）。在第三水平中出现 5 名完全供体嵌合体后，按照计划完成了研究。
mCRM 被证明是一种用于确定预处理方案剂量的相关方法。135mg/m2 的美法仑剂量被确定为诱导初始完全供体嵌合体的推荐 II 期剂量。
