Dey B R, McAfee S, Sackstein R, Colby C, Saidman S, Weymouth D, Poliquin C, Vanderklish J, Sachs D H, Sykes M, Spitzer T R
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Biol Blood Marrow Transplant. 2001;7(11):604-12. doi: 10.1053/bbmt.2001.v7.pm11760148.
The use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancy after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We evaluated the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in 13 patients (median age, 38 years) with relapsed hematologic malignancies (Hodgkin's disease, n = 4; Hodgkin's disease and advanced myelodysplastic syndrome, n = 1; non-Hodgkin's lymphoma, n = 6; multiple myeloma, n = 2) after initial autoSCT. Median time from autoSCT to alloSCT was 12 months (range, 3-24 months); 6 patients had chemotherapy-refractory disease following autoSCT, 6 were in untreated relapse, and 1 had a partial response from salvage chemotherapy. Preparative therapy consisted of cyclophosphamide, 150-200 mg/kg; peritransplantation anti-thymocyte globulin; thymic irradiation (in patients who had not received previous mediastinal irradiation); and a very short course of cyclosporine as GVHD prophylaxis. All patients achieved initial mixed chimerism as defined by greater than 1% donor peripheral white blood cells. Seven patients, who had no evidence of GVHD, received prophylactic DLI beginning 5 to 6 weeks after transplantation for conversion of mixed chimerism to full donor hematopoiesis and to optimize a graft-versus-tumor effect. Six patients showed conversion to full donor chimerism and 1 lost the graft. Grade II or greater acute GVHD occurred in 9 patients. Seven patients achieved a complete response; 6 had no response. The median survival time of the 13 patients is currently 10 months (range, 3-39 months), with an overall survival probability at 2 years of 45% (95% confidence interval [CI], 19%-73%) and a disease-free survival probability at 2 years of 37.5% (95% CI, 12%-65%). Thus, this novel nonmyeloablative alloSCT strategy followed by prophylactic DLI was well tolerated and can result in durable disease-free survival among patients with advanced hematologic malignancies after a failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in the treatment of hematologic malignancies after an autologous transplantation.
对于自体干细胞移植（autoSCT）后复发的血液系统恶性肿瘤成年患者，采用清髓性预处理疗法和异基因干细胞移植（alloSCT）作为挽救性治疗，通常因治疗相关死亡率极高而不成功。我们评估了13例（中位年龄38岁）初始autoSCT后复发的血液系统恶性肿瘤（霍奇金淋巴瘤，n = 4；霍奇金淋巴瘤和晚期骨髓增生异常综合征，n = 1；非霍奇金淋巴瘤，n = 6；多发性骨髓瘤，n = 2）患者在非清髓性预处理疗法后接受HLA匹配的相关供体alloSCT的结果。从autoSCT到alloSCT的中位时间为12个月（范围3 - 24个月）；6例患者在autoSCT后患有化疗难治性疾病，6例处于未治疗的复发状态。1例对挽救性化疗有部分反应。预处理疗法包括环磷酰胺，150 - 200 mg/kg；移植前抗胸腺细胞球蛋白；胸腺照射（未接受过先前纵隔照射的患者）；以及极短疗程的环孢素用于预防移植物抗宿主病（GVHD）。所有患者均达到初始混合嵌合状态，定义为供体外周白细胞大于1%。7例无GVHD证据的患者在移植后5至6周开始接受预防性供体淋巴细胞输注（DLI），以将混合嵌合状态转化为完全供体造血并优化移植物抗肿瘤效应。6例患者显示转化为完全供体嵌合状态，1例失去移植物。9例患者发生II级或更高级别的急性GVHD。7例患者获得完全缓解；6例无反应。13例患者的中位生存时间目前为10个月（范围3 - 39个月），2年总生存概率为45%（95%置信区间[CI]，19% - 73%），2年无病生存概率为37.5%（95% CI，12% - 65%）。因此，这种新型的非清髓性alloSCT策略继以防性DLI耐受性良好，可使autoSCT失败后的晚期血液系统恶性肿瘤患者实现持久的无病生存。需要对更多患者进行进一步随访和评估，以最终确定该策略在自体移植后血液系统恶性肿瘤治疗中的作用。
