Mohammad Ramzi M, Aboukameel Amro, Nabha Sanaa, Ibrahim Dina, Al-Katib Ayad
Department of Internal Medicine, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI 48201, USA.
J Drug Target. 2002 Aug;10(5):405-10. doi: 10.1080/1061186021000001850.
Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the antitumor effects of Rituximab (RTX), Cyclophosphamide (CTX), Dexamethasone (DEX) [RCD]-Regimen in vivo WSU-WM SCID xenograft and in a patient with WM. For the pre-clinical efficacy study, WSU-WM-bearing SCID mice were randomly assigned to receive RTX (150 mg/kg/inj, i.v., QDX5), CTX (90 mg/kg/inj, s.c. QDX5) as single agents or diluent. The combination group received RTX at 150 mg/kg/inj, QDX5; CTX at 150 mg/kg/inj, QODX3 and DEX at 1.0 mg/kg/inj, i.v., QDX5. Tumor growth inhibition (T/C), tumor growth delay (T - C), and log10 kill (net) for RTX and CTX were 24.5%, 37 days, 5.52 and 88%, 0.0 days, 0.0log10 kill, respectively. No cures were observed with either agent; however, all mice (6/6, with bilateral tumors) were cured when treated with RCD-regimen. A 57-year-old patient with relapsed WM was treated with the RCD-regimen and showed an excellent partial remission for seven months. The patient tolerated the treatment very well, the hemoglobin improved dramatically, platelets remained stable, the IgM level normalized and there was only minimal involvement of bone marrow. Based on these results, the RCD regimen is effective against WM and its activity should be further evaluated in clinical trials.
华氏巨球蛋白血症（WM）是一种罕见的淋巴增殖性疾病，目前的治疗方案仍无法将其治愈。我们之前建立了一个永久性的WM细胞系WSU-WM，该细胞系在严重联合免疫缺陷（SCID）小鼠体内可作为异种移植瘤生长。在本研究中，我们调查了利妥昔单抗（RTX）、环磷酰胺（CTX）、地塞米松（DEX）组成的[RCD]方案对体内WSU-WM SCID异种移植瘤以及一名WM患者的抗肿瘤作用。对于临床前疗效研究，将携带WSU-WM的SCID小鼠随机分配接受RTX（150mg/kg/注射，静脉注射，每5天一次）、CTX（90mg/kg/注射，皮下注射，每5天一次）作为单药治疗或稀释剂。联合治疗组接受RTX 150mg/kg/注射，每5天一次；CTX 150mg/kg/注射，每3天一次，以及DEX 1.0mg/kg/注射，静脉注射，每5天一次。RTX和CTX的肿瘤生长抑制率（T/C）、肿瘤生长延迟时间（T - C）和对数杀灭率（净）分别为24.5%、37天、5.52以及88%、0.0天、0.0对数杀灭率。单药治疗均未观察到治愈情况；然而，当用[RCD]方案治疗时，所有小鼠（6/6，双侧有肿瘤）均被治愈。一名57岁复发WM患者接受[RCD]方案治疗后，出现了长达7个月的优异部分缓解。患者对治疗耐受性良好，血红蛋白显著改善，血小板保持稳定，IgM水平恢复正常，骨髓仅有轻微受累。基于这些结果，[RCD]方案对WM有效，其活性应在临床试验中进一步评估。
