Olivieri Attilio, Lucesole Moira, Capelli Debora, Gini Guido, Montanari Mauro, Candela Marco, Troiani Emanuela, Scortechini Ilaria, Poloni Antonella, Leoni Pietro
Department of Hematology, University of Ancona, Ancona, Italy.
Biol Blood Marrow Transplant. 2005 Aug;11(8):627-36. doi: 10.1016/j.bbmt.2005.05.002.
From 1999 to 2002, 20 patients with aggressive non-Hodgkin lymphoma, among 28 who failed autologous peripheral blood progenitor cell transplantation, were rescued with cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisone (CHOP)/rituximab (RTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). RTX was administered twice during each course of chemotherapy, before CHOP and after GM-CSF. This cytokine was given to increase the antibody-dependent cell-mediated cytotoxicity and to reduce the leukopenia on the basis of our preliminary data, which suggested that this cytokine can upregulate CD20 expression. The relevant (World Health Organization grade 3-4) toxicity mainly consisted of myelosuppression (neutropenia in 60% of patients). Fifteen patients achieved complete remission (CR) or had a partial response, with an overall response rate of 75% (60% CR and 15% partial response). Six of the 12 patients who achieved CR relapsed: 2 died of progressive disease, 1 died of infectious complications after allogeneic transplantation, and 3 are alive in second CR. Eight patients showed progressive disease: 5 died of progressive disease, 1 of secondary acute leukemia, and 1 of infectious complications after allogeneic transplantation, whereas 1 is alive in second CR. At last follow-up, 10 patients are alive, 6 of whom are in complete continuous remission, with a median follow-up of 31 months (range, 3-51 months). The projected 4-year progression-free survival is 31.4%, and the 4-year overall survival is 50%. This new association (RTX, CHOP, and GM-CSF) was feasible in approximately 70% of patients; the overall toxicity was manageable. The good response rate and the promising outcome observed in this subset of patients could be explained by the possible increased synergy between chemotherapy, RTX, and GM-CSF, which should be explored in further studies.
1999年至2002年期间,在28例自体外周血祖细胞移植失败的患者中,20例侵袭性非霍奇金淋巴瘤患者接受了环磷酰胺、羟基柔红霉素、长春新碱和泼尼松(CHOP)/利妥昔单抗(RTX)以及粒细胞巨噬细胞集落刺激因子(GM-CSF)治疗以获得挽救。RTX在每个化疗疗程中给药两次,分别在CHOP之前和GM-CSF之后。基于我们的初步数据给予这种细胞因子以增加抗体依赖性细胞介导的细胞毒性并减少白细胞减少,初步数据表明这种细胞因子可上调CD20表达。相关的(世界卫生组织3 - 4级)毒性主要包括骨髓抑制(60%的患者出现中性粒细胞减少)。15例患者达到完全缓解(CR)或部分缓解,总缓解率为75%(60% CR和15%部分缓解)。达到CR的12例患者中有6例复发:2例死于疾病进展,1例在异基因移植后死于感染并发症,3例处于第二次CR状态存活。8例患者疾病进展:5例死于疾病进展,1例死于继发性急性白血病,1例在异基因移植后死于感染并发症,但1例处于第二次CR状态存活。在最后一次随访时,10例患者存活,其中6例处于完全持续缓解状态,中位随访时间为31个月(范围3 - 51个月)。预计4年无进展生存率为31.4%,4年总生存率为50%。这种新的联合方案(RTX、CHOP和GM-CSF)在大约70%的患者中是可行的;总体毒性是可控制的。在这部分患者中观察到的良好缓解率和有前景的结果可能是由于化疗、RTX和GM-CSF之间可能增加的协同作用,这应在进一步研究中进行探索。