Sorror Mohamed L, Maris Michael B, Sandmaier Brenda M, Storer Barry E, Stuart Monic J, Hegenbart Ute, Agura Edward, Chauncey Thomas R, Leis Jose, Pulsipher Michael, McSweeney Peter, Radich Jerald P, Bredeson Christopher, Bruno Benedetto, Langston Amelia, Loken Michael R, Al-Ali Haifa, Blume Karl G, Storb Rainer, Maloney David G
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
J Clin Oncol. 2005 Jun 1;23(16):3819-29. doi: 10.1200/JCO.2005.04.569. Epub 2005 Apr 4.
Patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) have a short life expectancy. The aim of this study was to analyze the outcome of patients with advanced CLL when treated with nonmyeloablative conditioning and hematopoietic cell transplantation (HCT).
Sixty-four patients diagnosed with advanced CLL were treated with nonmyeloablative conditioning (2 Gy total-body irradiation with [n = 53] or without [n = 11] fludarabine) and HCT from related (n = 44) or unrelated (n = 20) donors. An adapted form of the Charlson comorbidity index was used to assess pretransplantation comorbidities.
Sixty-one of 64 patients had sustained engraftment, whereas three patients rejected their grafts. The incidences of grades 2, 3, and 4 acute and chronic graft-versus-host disease were 39%, 14%, 2%, and 50%, respectively. Three patients who underwent transplantation in complete remission (CR) remained in CR. The overall response rate among 61 patients with measurable disease was 67% (50% CR), whereas 5% had stable disease. All patients with morphologic CR who were tested by polymerase chain reaction (n = 11) achieved negative molecular results, and one of these patients subsequently experienced disease relapse. The 2-year incidence of relapse/progression was 26%, whereas the 2-year relapse and nonrelapse mortalities were 18% and 22%, respectively. Two-year rates of overall and disease-free survivals were 60% and 52%, respectively. Unrelated HCT resulted in higher CR and lower relapse rates than related HCT, suggesting more effective graft-versus-leukemia activity.
CLL is susceptible to graft-versus-leukemia effects, and allogeneic HCT after nonmyeloablative conditioning might prolong median survival for patients with advanced CLL.
化疗难治性慢性淋巴细胞白血病(CLL)患者预期寿命较短。本研究旨在分析晚期CLL患者接受非清髓性预处理和造血细胞移植(HCT)后的结局。
64例诊断为晚期CLL的患者接受了非清髓性预处理(53例接受2 Gy全身照射加氟达拉滨,11例仅接受2 Gy全身照射),并接受了来自相关供者(44例)或无关供者(20例)的HCT。采用改良的Charlson合并症指数评估移植前合并症。
64例患者中有61例实现持续植入,3例患者移植失败。2级、3级和4级急慢性移植物抗宿主病的发生率分别为39%、14%、2%和50%。3例在完全缓解(CR)状态下接受移植的患者仍处于CR状态。61例有可测量疾病的患者的总体缓解率为67%(50%为CR),5%为病情稳定。所有经聚合酶链反应检测达到形态学CR的患者(n = 11)分子结果均为阴性,其中1例患者随后疾病复发。复发/进展的2年发生率为26%,2年复发死亡率和非复发死亡率分别为18%和22%。2年总生存率和无病生存率分别为60%和52%。无关供者HCT比相关供者HCT导致更高的CR率和更低的复发率,提示移植物抗白血病活性更强。
CLL易受移植物抗白血病效应影响,非清髓性预处理后的异基因HCT可能延长晚期CLL患者的中位生存期。