Fung H C, Cohen S, Rodriguez R, Smith D, Krishnan A, Somlo G, Sahebi F, Senitzer D, O'Donnell M R, Stein A, Snyder D S, Spielberger R, Bhatia R, Falk P, Molina A, Nademanee A, Parker P, Kogut N, Popplewell L, Vora N, Margolin K, Forman S J
Division of Hematology and Bone Marrow Transplantation, Kaiser Permanente-City of Hope BMT Program, City of Hope Cancer Center, 1500 E. Duarte Road, Duarte, CA 91010, USA.
Biol Blood Marrow Transplant. 2003 Oct;9(10):649-56. doi: 10.1016/s1083-8791(03)00241-6.
Autologous hematopoietic stem cell transplantation (autoSCT) is an effective treatment for patients with various hematologic malignancies. Despite the significant improvement in the overall outcome, disease progression after transplantation remains the major cause of treatment failure. With longer follow-up, therapy-related myelodysplasia/acute myelogenous leukemia is becoming an important cause of treatment failure. The prognosis for these 2 groups of patients is very poor. Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potential curative treatment for these patients. However, the outcome with conventional myeloablative alloSCT after failed autoSCT is typically poor because of high transplant-related mortality. In an attempt to reduce the treatment-related toxicity, we studied a reduced-intensity conditioning regimen followed by alloSCT for patients with progressive disease or therapy-related myelodysplasia/acute myelogenous leukemia after autoSCT. This report describes the outcomes of 28 patients with hematologic malignancies who received a reduced-intensity alloSCT after having treatment failure with a conventional autoSCT. Fourteen patients received a hematopoietic stem cell transplant from a related donor and 14 from an unrelated donor. The conditioning regimen consisted of low-dose (2 Gy) total body irradiation with or without fludarabine in 4 patients and the combination of melphalan (140 mg/m(2)) and fludarabine in 24. Cyclosporine and mycophenolate mofetil were used for posttransplantation immunosuppressive therapy, as well as graft-versus-host disease (GVHD) prophylaxis, in all patients. All patients engrafted and had >90% donor chimerism on day 100 after SCT. Currently, 13 patients (46%) are alive and disease free, 7 patients (25%) developed disease progression after alloSCT, and 8 (32%) died of nonrelapse causes. Day 100 mortality and nonrelapse mortality were 25% and 21%, respectively. With a median follow-up of 24 months for surviving patients, the 2-year probabilities of overall survival, event-free survival, and relapse rates were 56.5%, 41%, and 41.9%, respectively. Six patients (21%) developed grade III to IV acute GVHD. Among 21 evaluable patients, 15 (67%) developed chronic GVHD. We conclude that (1) reduced-intensity alloSCT is feasible and has an acceptable toxicity profile in patients who have previously received autoSCT and that (2) although follow-up was short, a durable remission may be achieved in some patients who would otherwise be expected to have a poor outcome.
自体造血干细胞移植（autoSCT）是治疗各种血液系统恶性肿瘤患者的有效方法。尽管总体疗效有了显著改善，但移植后疾病进展仍然是治疗失败的主要原因。随着随访时间的延长，治疗相关的骨髓增生异常综合征/急性髓系白血病正成为治疗失败的重要原因。这两组患者的预后都非常差。异基因造血干细胞移植（alloSCT）是这些患者的一种潜在治愈性治疗方法。然而，自体造血干细胞移植失败后进行传统清髓性异基因造血干细胞移植的疗效通常较差，因为移植相关死亡率较高。为了降低治疗相关毒性，我们研究了一种减低强度预处理方案，随后对自体造血干细胞移植后疾病进展或治疗相关骨髓增生异常综合征/急性髓系白血病患者进行异基因造血干细胞移植。本报告描述了28例血液系统恶性肿瘤患者在传统自体造血干细胞移植治疗失败后接受减低强度异基因造血干细胞移植的结果。14例患者接受了来自相关供体的造血干细胞移植，14例来自无关供体。预处理方案包括4例患者接受低剂量（2 Gy）全身照射，其中2例联合氟达拉滨，24例采用美法仑（140 mg/m²）和氟达拉滨联合方案。所有患者移植后均使用环孢素和霉酚酸酯进行免疫抑制治疗以及预防移植物抗宿主病（GVHD）。所有患者均成功植入，移植后100天供体嵌合率>90%。目前，13例患者（46%）存活且无疾病，7例患者（25%）异基因造血干细胞移植后疾病进展，8例（32%）死于非复发原因。移植后100天死亡率和非复发死亡率分别为25%和21%。存活患者的中位随访时间为24个月，2年总生存率、无事件生存率和复发率分别为56.5%、41%和41.9%。6例患者（21%）发生Ⅲ至Ⅳ级急性移植物抗宿主病。在21例可评估患者中，15例（67%）发生慢性移植物抗宿主病。我们得出结论：（1）减低强度异基因造血干细胞移植对于先前接受过自体造血干细胞移植的患者是可行的，且毒性可接受；（2）尽管随访时间较短，但一些原本预期预后较差的患者可能实现持久缓解。
