Haas R, Brittinger G, Meusers P, Murea S, Goldschmidt H, Wannenmacher M, Hunstein W
Department of Internal Medicine V, University of Heidelberg, Germany.
Leukemia. 1996 Dec;10(12):1975-9.
Long-term disease-free survival following conventional cytotoxic therapy is extremely rare in patients with advanced-stage mantle cell lymphoma (MCL). High-dose conditioning therapy consisting of hyperfractionated total body irradiation (TBI, 14.4 Gy) and cyclophosphamide (200 mg/kg) was therefore offered to 13 patients (four females/nine males) with advanced-stage MCL. The patients were relatively young with a median age of 49 years (range 30-60). High-dose cytarabine and mitoxantrone with granulocyte colony-stimulating factor (G-CSF) support were given for second-line therapy and mobilization of peripheral blood stem cells (PBSC). During cytokine-stimulated marrow recovery, a median of two leukaphereses (range 1-4) were performed. Using direct immunofluorescence analysis including two-color staining, the proportion of CD19+ B cells and CD34+/CD19+ B lymphoid progenitor cells was found to be extremely low with quantities below detection limit in approximately 50% of the autografts. At the time of autografting, nine patients (pts) were in first partial (five pts) or complete (four pts) remission, while four patients had achieved a second complete remission. Following myeloablative therapy a median number of 7.5 x 10(6) CD34+ cells/kg were autografted. The median time for neutrophil (> or = 0.5 x 10(9)/l) and platelet recovery (> or = 20 x 10(9)/l) was 13 and 10 days, respectively. Hematological recovery was delayed in a patient who received 5.8 x 10(6) positively selected CD34+ cells/kg. There was one toxic death 17 days post-transplantation because of overwhelming interstitial pneumonia. Two patients with a history of previous treatment failure relapsed 10 and 11 months post-transplantation, respectively, at sites of previous disease. Ten patients are disease-free with a median follow-up time of 18 months (range 10-47). The results presented here suggest that PBSC-supported high-dose therapy including TBI may provide long-term disease-free survival for patients with advanced-stage mantle cell lymphoma.
对于晚期套细胞淋巴瘤(MCL)患者,采用传统细胞毒性疗法后长期无病生存极为罕见。因此,对13例(4例女性/9例男性)晚期MCL患者进行了由超分割全身照射(TBI,14.4 Gy)和环磷酰胺(200 mg/kg)组成的大剂量预处理疗法。患者相对年轻,中位年龄为49岁(范围30 - 60岁)。给予大剂量阿糖胞苷和米托蒽醌并辅以粒细胞集落刺激因子(G-CSF)进行二线治疗及外周血干细胞(PBSC)动员。在细胞因子刺激的骨髓恢复期间,平均进行了两次白细胞分离术(范围1 - 4次)。通过包括双色染色在内的直接免疫荧光分析发现,在大约50%的自体移植物中,CD19 + B细胞和CD34 + /CD19 + B淋巴祖细胞的比例极低,数量低于检测限。在进行自体移植时,9例患者处于首次部分缓解(5例)或完全缓解(4例),而4例患者实现了第二次完全缓解。清髓性治疗后,平均每千克自体移植7.5×10⁶个CD34 + 细胞。中性粒细胞(≥0.5×10⁹/L)和血小板恢复(≥20×10⁹/L)的中位时间分别为13天和10天。一名接受每千克5.8×10⁶个阳性选择的CD34 + 细胞的患者血液学恢复延迟。移植后17天有1例因严重间质性肺炎发生毒性死亡。2例有既往治疗失败史的患者分别在移植后10个月和11个月于既往疾病部位复发。10例患者无病生存,中位随访时间为18个月(范围10 - 47个月)。此处呈现的结果表明,包括TBI在内的PBSC支持的大剂量疗法可能为晚期套细胞淋巴瘤患者提供长期无病生存。