Demirer T, Buckner C D, Appelbaum F R, Clift R, Storb R, Myerson D, Lilleby K, Rowley S, Bensinger W I
Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle 98104, USA.
Bone Marrow Transplant. 1996 May;17(5):769-74.
This study was conducted to evaluate the efficacy of high-dose busulfan (BU) and cyclophosphamide (CY) in patients undergoing autologous hematopoietic stem cell transplantation for metastatic breast cancer. Twenty-two patients with stage IV breast cancer underwent autologous marrow (n = 13), peripheral blood stem cell (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16 mg/kg) and CY (120-180 mg/kg). Of 22 patients, 18 had refractory relapse, one had primary refractory disease, two had responding relapse and one had no evidence of disease (NED) at the time of transplant. Eight patients had bone only disease, six had bone plus visceral disease, and eight had loco-regional recurrent disease. The median time for diagnosis to transplant was 1124 days (range 210-2582). Staging for evaluation of response was performed 4-6 months after transplantation. Six patients were not evaluable (NE) for response because of NED at transplant (n = 1) or early death due to transplant-related complications (n = 5) (one of RSV interstitial pneumonia, two of fungal infection and two of regimen-related toxicities) occurring at a median of 17 days (range 14-59) post-transplant. The patient who was NED at time of transplant is still NED on day 336 post-transplant. Seven of the 16 evaluable patients achieved a complete response (CR) (44%), five achieved a partial response (PR) (31%) and five had no response (NR), with an overall response rate of 75%. Five of 18 (28%) patients treated in refractory relapse, and both patients treated in responding relapse achieved a CR. Of the seven patients who achieved CR, three are alive and disease-free on days 204, 276 and 752 and three relapsed on days 209, 715 and 1127 post-transplant. One patient in CR died of aspergillus pneumonia on day 306 post-transplant. The median day to progression in five patients who achieved a PR after transplantation was 335 (range 144-507). The probabilities of survival and event-free survival (EFS) at 2 years was 0.22 and 0.15, respectively for all 22 patients. The probability of EFS at 2 years for the eight patients achieving CR (including one patient who was NED at transplant) was 0.33. The probabilities of overall survival at 2 years in patients who did and did not achieve a CR after transplantation was 0.63 and 0.14, respectively (P = 0.004). These data suggest that high-dose BU-CY followed by autologous stem cell transplantation is an effective regimen in patients with advanced breast cancer demonstrating that BU is an active agent in this disease and could be incorporated into treatment regimens requiring hematopoietic stem cell support.
本研究旨在评估大剂量白消安（BU）和环磷酰胺（CY）在转移性乳腺癌患者自体造血干细胞移植中的疗效。22例IV期乳腺癌患者在接受白消安（14 - 16mg/kg）和环磷酰胺（120 - 180mg/kg）治疗后，进行了自体骨髓移植（n = 13）、外周血干细胞移植（PBSC）（n = 6）或骨髓加外周血干细胞移植（n = 3）。22例患者中，18例为难治性复发，1例为原发性难治性疾病，2例为反应性复发，1例在移植时无疾病证据（NED）。8例患者仅有骨转移，6例患者有骨转移加内脏转移，8例患者有局部区域复发。从诊断到移植的中位时间为1124天（范围210 - 2582天）。移植后4 - 6个月进行反应评估分期。6例患者因移植时处于NED状态（n = 1）或移植相关并发症导致的早期死亡（n = 5）（1例呼吸道合胞病毒间质性肺炎、2例真菌感染和2例方案相关毒性）而无法评估反应，这些并发症发生在移植后中位时间17天（范围14 - 59天）。移植时处于NED状态的患者在移植后336天仍处于NED状态。16例可评估患者中，7例达到完全缓解（CR）（44%），5例达到部分缓解（PR）（31%），5例无反应（NR），总反应率为75%。18例难治性复发患者中有5例（28%）以及2例反应性复发患者均达到CR。在达到CR的7例患者中，3例在移植后204天、276天和752天存活且无疾病，3例在移植后209天、715天和1127天复发。1例CR患者在移植后306天死于曲霉菌性肺炎。移植后达到PR的5例患者的疾病进展中位天数为335天（范围144 - 507天）。22例患者2年时的生存率和无事件生存率（EFS）分别为0.22和0.15。8例达到CR的患者（包括1例移植时处于NED状态的患者）2年时的EFS概率为0.33。移植后达到CR和未达到CR的患者2年时的总生存率分别为0.63和0.14（P = 0.004）。这些数据表明，大剂量BU - CY序贯自体干细胞移植对晚期乳腺癌患者是一种有效的方案，表明白消安在该疾病中是一种活性药物，可纳入需要造血干细胞支持的治疗方案中。
