Department of Stem-Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030.
Biol Blood Marrow Transplant. 2012 Nov;18(11):1677-86. doi: 10.1016/j.bbmt.2012.05.011. Epub 2012 May 27.
We developed a new high-dose combination of infusional gemcitabine with busulfan and melphalan for lymphoid tumors. Gemcitabine dose was escalated by extending infusions at a fixed rate of 10 mg/m(2)/min in sequential cohorts, in daily, 3-dose or 2-dose schedules. Each gemcitabine dose immediately preceded busulfan (adjusted targeting area under the curve 4,000 μM/min(-1)/day × 4 days) or melphalan (60 mg/m(2)/day × 2 days). We enrolled 133 patients (80 Hodgkin lymphoma [HL], 46 non-Hodgkin lymphoma [NHL], 7 myeloma), median 3 prior regimens; primary refractory disease in 63% HL/45% NHL and positron emission tomography positive tumors at transplantation in 50% patients. Two patients died from early posttransplantation infections. The major toxicity was mucositis. The daily and 3-dose schedules caused substantial cutaneous toxicity. In contrast, the 2-dose schedule was better tolerated, which allowed us to extend the infusions from 15 to 270 minutes. Pretransplantation values of C-reactive protein, B-type natriuretic peptide, ferritin, or haptoglobin did not correlate with toxicity. Overall response and complete response rates were 87%/62% (HL), 100%/69% B large-cell lymphoma (B-LCL), 66%/66% (T-NHL), and 71%/57% (myeloma). At median follow-up of 24 months (range, 3-63 months), the event-free/overall survival rates were 54%/72% (HL), 60%/89% (B-LCL), 70%/70% (T-NHL), and 43%/43% (myeloma). In conclusion, gemcitabine/busulfan/melphalan is a feasible regimen with substantial activity against a range of lymphoid malignancies. This regimen merits further evaluation in phase II and III trials.
我们开发了一种新的高剂量组合方案，即吉西他滨联合白消安和马法兰用于治疗淋巴肿瘤。吉西他滨剂量通过在固定的 10mg/m2/分钟的输注速率下，以连续队列的方式递增，每天输注 3 剂或 2 剂。每个吉西他滨剂量都紧随白消安（调整靶向曲线下面积 4000μM/min·天×4 天）或马法兰（60mg/m2/天×2 天）之后。我们共纳入了 133 例患者（80 例霍奇金淋巴瘤[HL]，46 例非霍奇金淋巴瘤[NHL]，7 例多发性骨髓瘤），中位既往治疗方案数为 3 个；63%的 HL/45%的 NHL 患者为原发耐药疾病，50%的患者在移植时 PET 阳性肿瘤。2 例患者死于早期移植后感染。主要毒性为黏膜炎。每日和 3 剂方案导致严重的皮肤毒性。相比之下，2 剂方案更耐受，允许我们将输注时间从 15 分钟延长至 270 分钟。移植前 C 反应蛋白、B 型利钠肽、铁蛋白或结合珠蛋白的值与毒性无关。总体缓解率和完全缓解率分别为 87%/62%（HL），100%/69%B 大细胞淋巴瘤（B-LCL），66%/66%（T-NHL）和 71%/57%（多发性骨髓瘤）。在中位随访 24 个月（范围 3-63 个月）时，无事件生存率/总生存率分别为 54%/72%（HL），60%/89%（B-LCL），70%/70%（T-NHL）和 43%/43%（多发性骨髓瘤）。总之，吉西他滨/白消安/马法兰是一种可行的方案，对多种淋巴恶性肿瘤具有显著的活性。该方案值得在 II 期和 III 期试验中进一步评估。
