环孢素诱导的自体移植物抗宿主病在接受大剂量化疗及自体干细胞解救的多发性骨髓瘤患者中的I期试验。

Phase I trial of cyclosporine-induced autologous graft-versus-host disease in patients with multiple myeloma undergoing high-dose chemotherapy with autologous stem-cell rescue.

作者信息

Giralt S, Weber D, Colome M, Dimopoulos M, Mehra R, Van Besien K, Gajewski J, Andersson B, Khouri I, Przepiorka D, von Wolff B, Delasalle K, Korbling M, Seong D, Alexanian R, Champlin R

机构信息

Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

出版信息

J Clin Oncol. 1997 Feb;15(2):667-73. doi: 10.1200/JCO.1997.15.2.667.

DOI:10.1200/JCO.1997.15.2.667

PMID:9053492

Abstract

PURPOSE

To determine the feasibility and toxicity of inducing autologous graft-versus-host disease (GVHD) with cyclosporine in patients with multiple myeloma undergoing autologous stem-cell transplantation.

PATIENTS AND METHODS

Fourteen multiple myeloma patients with a median age of 50 years (range, 41 to 63) were enrolled. The median time from diagnosis to transplant was 651 days (range, 229 to 3,353). Ten patients had primary refractory disease, two were in first remission, and two were responsive to salvage therapy. The preparative regimen consisted of thiotepa, busulfan, and cyclophosphamide. Cyclosporine was administered daily for 28 days after the stem-cell infusion, and the dose was adjusted to maintain whole-blood cyclosporine levels between 50 and 150 ng/dL in the first seven patients (low-level group) and between 150 and 300 ng/dL in the other seven patients (high-level group).

RESULTS

All patients achieved neutrophil engraftment a median of 11 days after transplant. Four patients developed > or = grade 2 hepatic toxicity, six developed > or = grade 2 nephrotoxicity, and four developed reversible cardiac toxicity. Only one treatment-related death occurred. Cyclosporine was withheld in seven patients for a median of 6 days because of renal and/or liver dysfunction. One patient developed clinical skin GVHD, which responded to corticosteroid therapy. Six patients developed histologic evidence of GVHD without clinical signs of GVHD (subclinical GVHD). The incidence of clinical and subclinical GVHD was similar in both cyclosporine groups. Three of 11 patients assessable for response achieved remissions. Three patients experienced disease progression 80, 160, and 354 days after transplant. Ten patients are alive without progression between 56 and 444 days after transplant.

CONCLUSION

Induction of autologous GVHD by posttransplant cyclosporine is feasible and well tolerated in patients with multiple myeloma.

摘要

目的

确定在接受自体干细胞移植的多发性骨髓瘤患者中，用环孢素诱导自体移植物抗宿主病（GVHD）的可行性和毒性。

患者与方法

纳入14例多发性骨髓瘤患者，中位年龄50岁（范围41至63岁）。从诊断到移植的中位时间为651天（范围229至3353天）。10例患者为原发性难治性疾病，2例处于首次缓解期，2例对挽救治疗有反应。预处理方案包括噻替派、白消安和环磷酰胺。干细胞输注后每天给予环孢素，共28天，前7例患者（低剂量组）的剂量调整为维持全血环孢素水平在50至150 ng/dL之间，另外7例患者（高剂量组）维持在150至300 ng/dL之间。

结果

所有患者均在移植后中位11天实现中性粒细胞植入。4例患者发生≥2级肝毒性，6例发生≥2级肾毒性，4例发生可逆性心脏毒性。仅发生1例与治疗相关的死亡。7例患者因肾和/或肝功能障碍而停用环孢素，中位停用时间为6天。1例患者发生临床皮肤GVHD，对皮质类固醇治疗有反应。6例患者出现GVHD的组织学证据，但无GVHD的临床体征（亚临床GVHD）。两个环孢素组的临床和亚临床GVHD发生率相似。11例可评估反应的患者中有3例实现缓解。3例患者在移植后80、160和354天出现疾病进展。10例患者在移植后56至444天存活且无疾病进展。