Buser A S, Heim D, Bucher C, Tichelli A, Gratwohl A, Passweg J R
Stem Cell Transplantation Team, Basel University Hospitals, Petersgraben 4, CH-4031 Basel, Switzerland.
Bone Marrow Transplant. 2004 May;33(10):1011-4. doi: 10.1038/sj.bmt.1704489.
In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.
在难治性淋巴瘤患者中，我们检验了以下假设：在无干细胞支持的情况下进行大剂量化疗（BEAM方案），28天后给予氟达拉滨和2 Gy全身照射的减低强度（RIC）异基因移植，可实现肿瘤细胞减灭并建立移植物抗淋巴瘤效应，且毒性可接受。在一项试验方案中，我们治疗了10例年龄在22 - 62岁（中位年龄47岁）的高危或难治性霍奇金淋巴瘤或非霍奇金淋巴瘤患者。供者为HLA相合的同胞（8例）或无关志愿者。在持续至RIC异基因造血干细胞移植的BEAM方案后的中性粒细胞减少期，无患者死亡。中性粒细胞减少持续时间为31 - 43天（中位36天）。所有患者均实现造血重建，9例达到完全缓解（CR）。所有患者均发生急性移植物抗宿主病（GvHD，中位III级），所有有风险的患者均发生慢性GvHD。3例患者死于GvHD。1例复发，6例患者在异基因造血干细胞移植后10 - 32个月（中位15个月）持续处于CR状态。这种方法似乎可行，且缓解率较高。中性粒细胞减少持续时间令人担忧。减灭性化疗与诱导异基因效应的分离是否具有优势仍有待检验。
