Vitolo U, Cortellazzo S, Liberati A M, Freilone R, Falda M, Bertini M, Botto B, Cinieri S, Levis A, Locatelli F, Lovisone E, Marmont F, Pizzuti M, Rossi A, Viero P, Barbui T, Grignani F, Resegotti L
Divisione di Ematologia Azienda Ospedaliera S. Giovanni Battista, Torino, Italy.
J Clin Oncol. 1997 Feb;15(2):491-8. doi: 10.1200/JCO.1997.15.2.491.
In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients.
Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both.
Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L.
This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.
在我们之前关于MACOPB方案的研究中，我们确定了一组高危患者，其3年生存率较低，为29%。这些患者被定义为在诊断时患有晚期疾病，肿瘤负荷（TB）高、乳酸脱氢酶（LDH）水平升高或有骨髓（BM）受累。我们研究了一种新的治疗方案以改善这些患者的治疗结果。
纳入50例高危弥漫性大细胞淋巴瘤（DLCL）患者。治疗方案包括三个阶段：8周的MACOPB诱导治疗；用米托蒽醌8 mg/m²加高三尖杉酯碱（HDARA-C）2 g/m²每12小时一次加地塞米松4 mg/m²每12小时一次（MAD方案）和粒细胞集落刺激因子（G-CSF）5 μg/kg在第4至17天进行强化治疗以采集外周血祖细胞（PBPC）；用卡莫司汀（BCNU）、依托泊苷、阿糖胞苷和马法兰（BEAM）方案进行巩固治疗；加用PBPC、骨髓或两者的自体干细胞移植（ASCT）。
36例患者（72%）达到完全缓解（CR），11例（22%）无反应（NR），3例（6%）死于毒性反应。在诱导期后的22例部分缓解（PR）或NR患者中，56%的患者在随后的强化治疗后达到CR。中位随访时间为32个月，总生存率和无失败生存率分别为56%和50%。32个月时无病生存率为69%。MAD方案和G-CSF治疗后白细胞单采术获得的CD34⁺细胞中位数为32×10⁶/kg，粒细胞-巨噬细胞集落形成单位（CFU-GM）为80×10⁴/kg。39例患者接受了自体移植，11例未进行ASCT：6例因疾病进展，4例因毒性反应，1例因患者拒绝。达到中性粒细胞计数大于0.5×10⁹/L的中位植入时间为11天（范围7至19天），血小板计数大于50×10⁹/L的中位植入时间为12天（范围8至60天）。
这种序贯方案联合强化和大剂量化疗及ASCT是可行的，毒性适中，可能改善高危DLCL患者的治疗结果。
