Jacobsohn David A, Chen Allen R, Zahurak Marianna, Piantadosi Steven, Anders Viki, Bolaños-Meade Javier, Higman Meghan, Margolis Jeffrey, Kaup Michele, Vogelsang Georgia B
Robert H. Lurie Comprehensive Cancer Center and Division of Hematology/Oncology/Transplant, Children's Memorial Hospital, Chicago, IL, USA.
J Clin Oncol. 2007 Sep 20;25(27):4255-61. doi: 10.1200/JCO.2007.10.8456.
Therapy for patients with chronic graft-versus-host disease (cGVHD) is based on prolonged immunosuppression with corticosteroids. There is no standard therapy for patients whose cGVHD does not resolve with corticosteroid treatment. Pentostatin, a potent inhibitor of adenosine deaminase, has activity in acute GVHD. We examined the toxicity and efficacy of pentostatin in a prospective phase II trial in corticosteroid-refractory cGVHD.
Patients of any age were eligible. Patients received pentostatin 4 mg/m2 intravenously every 2 weeks for 12 doses, and continued therapy as long as benefit was documented. Corticosteroid taper was begun after three doses of pentostatin. Responses were graded in real time in the skin, mouth, and liver using objective response criteria.
Fifty-eight heavily pretreated (median, four prior regimens) patients (median age, 33 years) were enrolled. Results are shown as an intent-to-treat analysis. Of the 58 patients, a total of 32 (55%; 95% CI, 42% to 68%) had an objective response, as evaluated by use of a new grading scale. Infection was the most significant toxicity, with 11 grade 3 to 4 infectious events. The survival at 1 and 2 years was 78% (95% CI, 64% to 86%) and 70% (95% CI, 57% to 80%), with cGVHD with/without infection accounting for the majority of deaths.
Pentostatin has immunosuppressive effects that are currently being explored further for treatment of cGVHD.
慢性移植物抗宿主病（cGVHD）患者的治疗基于长期使用皮质类固醇进行免疫抑制。对于皮质类固醇治疗无法缓解cGVHD的患者，尚无标准治疗方法。喷司他丁是一种有效的腺苷脱氨酶抑制剂，在急性移植物抗宿主病中有活性。我们在一项针对皮质类固醇难治性cGVHD的前瞻性II期试验中研究了喷司他丁的毒性和疗效。
任何年龄的患者均符合条件。患者每2周静脉注射4mg/m²喷司他丁，共12剂，只要有获益记录就继续治疗。在注射三剂喷司他丁后开始逐渐减少皮质类固醇用量。使用客观反应标准实时对皮肤、口腔和肝脏的反应进行分级。
纳入了58例经过大量预处理（中位值，4种先前治疗方案）的患者（中位年龄33岁）。结果以意向性分析呈现。在这58例患者中，共有32例（55%；95%CI，42%至68%）通过使用新的分级量表评估有客观反应。感染是最显著的毒性反应，有11例3至4级感染事件。1年和2年生存率分别为78%（95%CI，64%至86%）和70%（95%CI，57%至80%），cGVHD伴/不伴感染是主要死因。
喷司他丁具有免疫抑制作用，目前正在进一步探索其用于治疗cGVHD的效果。
