Khouri I F, Keating M, Körbling M, Przepiorka D, Anderlini P, O'Brien S, Giralt S, Ippoliti C, von Wolff B, Gajewski J, Donato M, Claxton D, Ueno N, Andersson B, Gee A, Champlin R
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Clin Oncol. 1998 Aug;16(8):2817-24. doi: 10.1200/JCO.1998.16.8.2817.
To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma.
Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present.
Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04).
These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.
研究以氟达拉滨为基础的非清髓性预处理方案，以产生足够的免疫抑制，使异基因干细胞得以植入，并诱导移植物抗白血病/淋巴瘤（GVL）效应，作为慢性淋巴细胞白血病（CLL）和淋巴瘤患者的主要治疗方式。
对15例患者进行了研究。6例患者处于晚期难治性复发阶段，2例患者诱导治疗失败。CLL或低度淋巴瘤患者接受90至150mg/m²的氟达拉滨和900至2000mg/m²的环磷酰胺治疗。中度淋巴瘤或Richter转化患者接受顺铂25mg/m²，每日1次，共4天；氟达拉滨30mg/m²；阿糖胞苷500mg/m²，每日1次，共2天。化疗后进行来自 HLA 配型相同同胞的异基因干细胞输注。如果不存在移植物抗宿主病（GVHD），移植后2至3个月，有残留恶性细胞或混合嵌合体的患者可接受0.5至2×10⁸个单核细胞/kg的供体淋巴细胞输注。
11例患者实现了供体细胞植入，其余4例患者迅速恢复了自体造血功能。11例患者中有8例达到完全缓解（CR）。6例化疗敏感疾病患者中有5例（83.3%）仍然存活，而研究入组时患有难治性或未经检测疾病的9例患者中有2例（22.2%）存活（P = 0.04）。
这些发现表明，采用非清髓性预处理方案进行异基因造血移植以实现植入并产生针对淋巴恶性肿瘤的GVL效应是可行的。在CLL、Richter转化以及低度和中度淋巴瘤患者中，通过供体淋巴细胞输注诱导缓解的能力是GVL对这些疾病具有活性的直接证据。这种方法在化疗反应性疾病且肿瘤负荷低的患者中似乎最有前景。
