FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors
FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors
复制标题
DOI：
10.1182/blood.v88.9.3634.bloodjournal8893634
复制
发表时间：
1996-11-01
期刊：
影响因子：
20.3
通讯作者：
Fay, JW
中科院分区：
文献类型：
--
作者：
Nash, RA;Pineiro, LA;Fay, JW
在两个中心进行的一项单臂II期研究中，评估了FK506与短程甲氨蝶呤(MTX)联合应用预防非血缘关系相合供者骨髓移植后急性移植物抗宿主病(GVHD)的安全性和潜在有效性。43名患者，年龄15-54岁(中位数41岁)，因血液系统恶性肿瘤而接受移植。在43名可评估的患者中，有37名患者有持续骨髓植入的证据。5例患者在移植后第17天前死亡。中性粒细胞绝对计数达到0.5x10(9)/L的中位时间为21天(14至30天)。32名患者发生肾毒性(血肌酐浓度2 mg/dL或基线的两倍)(移植后前100天的累积发生率为74%)。其他不良反应包括高血压(n=27)、高血糖(n=27)、神经毒性(n=9)和血栓性血小板减少性紫癜(n=2)。43例患者中有9例(21%)出现严重的肝静脉闭塞症。18名患者(42%)发展为II-IV级急性GVHD，5名(12%)发展为III-IV级急性GVHD。在25名可评估的患者中，有12名在骨髓移植后一年内发生了广泛的慢性移植物抗宿主病，因此发生这种并发症的可能性估计为48%。移植相关死亡率在前100天的累积发生率为37%。Kaplan-Meier估计好风险、差风险和所有患者的两年无病生存率分别为65%、4%和32%。FK506联合短程MTX对预防非亲缘供者骨髓移植后急性移植物抗宿主病有积极作用。FK506、MTX与环孢素、MTX联合应用预防急性移植物抗宿主病值得进一步研究。(C)1996年由美国血液病学会主办。
The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of >0.5x10(9)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration >2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n=27), hyperglycemia (n=27), neurotoxicity (n=9) and thrombotic thrombocytopenic purpura (n=2). Severe veno-occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan-Meier estimates of disease-free survival at 2 years for good-risk, poor-risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted. (C) 1996 by The American Society of Hematology.