Hallemeier C, Girgis M, Blum W, Brown R, Khoury H, Goodnough L T, Vij R, Devine S, Wehde M, Postma S, Lin H-S, Dipersio J, Adkins D
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Biol Blood Marrow Transplant. 2004 May;10(5):310-9. doi: 10.1016/j.bbmt.2003.12.002.
On the basis of observations from dog models and human studies, we hypothesized that a low-dose (550 cGy), single-exposure total body irradiation (TBI)-based regimen would result in improved survival when given to adult patients with acute myelogenous leukemia (AML) who were undergoing unrelated donor bone marrow transplantation in complete remission (CR). The regimen consisted of single exposure (550 cGy) of TBI given at a high dose rate (30 cGy/min) and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of cyclosporine, methotrexate, and corticosteroids. Thirty-two consecutive adult patients (median age, 47 years) with AML in CR (15 in CR 1 and 17 in CR > or =2) were treated. Sixteen patients (50%) were alive and in remission at last follow-up (median, 2.2 years; range, 0.6-4.0 years). Kaplan-Meier estimates of overall and leukemia-free survival at 3 years were 55% +/- 14% (mean +/- SE) and 57% +/- 14% in CR 1 patients and were both 39% +/- 12% in CR > or =2 patients. Transplant-related mortality was 13% for patients in CR 1 and 41% for those in CR > or =2. Only 1 patient (3%) experienced fatal regimen-related organ toxicity, and only 1 had grade III or IV acute graft-versus-host disease. Graft failure was not observed. Relapse occurred in 22% of patients. This low-dose (550 cGy), single-exposure TBI-based regimen resulted in good survival and a low risk of fatal regimen-related organ toxicity in adult patients with AML who underwent unrelated donor bone marrow transplantation in CR.
基于对犬模型和人体研究的观察,我们推测,对于处于完全缓解期(CR)并接受非亲缘供者骨髓移植的成年急性髓系白血病(AML)患者,采用低剂量(550 cGy)单次全身照射(TBI)方案会提高生存率。该方案包括以高剂量率(30 cGy/分钟)进行单次(550 cGy)TBI照射及环磷酰胺治疗。移植物抗宿主病预防措施包括环孢素、甲氨蝶呤和皮质类固醇。连续32例处于CR期的成年AML患者(中位年龄47岁)接受了治疗(CR1期15例,CR≥2期17例)。16例患者(50%)在最后一次随访时存活且处于缓解状态(中位随访时间2.2年;范围0.6 - 4.0年)。CR1期患者3年总生存率和无白血病生存率的Kaplan-Meier估计值分别为55%±14%(均值±标准误)和57%±14%,CR≥2期患者均为39%±12%。CR1期患者的移植相关死亡率为13%,CR≥2期患者为41%。仅1例患者(3%)出现致命的与方案相关的器官毒性,仅1例发生III或IV级急性移植物抗宿主病。未观察到移植物失败情况。22%的患者出现复发。对于处于CR期并接受非亲缘供者骨髓移植的成年AML患者,这种基于低剂量(550 cGy)单次TBI的方案可带来良好的生存率,且与方案相关的致命器官毒性风险较低。