Evaluation of Cellular and Humoral Immunity Against Myel

尽管大剂量放化疗联合自体干细胞移植在治疗患者方面显示出一定的前景。对于多发性骨髓瘤，潜在疾病的复发仍然是治疗失败的主要原因。这是一项初步研究，旨在探索主动特异性免疫治疗可能有效消除高剂量治疗后残留的微小残留疾病的可能性。患者实验研究。已经证明了免疫球蛋白独特型作为肿瘤特异性抗原用于开发针对B细胞恶性肿瘤的治疗性疫苗的可行性。重量份将在高剂量治疗前后的几个时间点用骨髓瘤独特型蛋白免疫，通过与载体（KLH）结合并与作为免疫佐剂的GM-CSF一起给药而产生免疫原性。本研究的目的是测试是否可以诱导细胞和体液免疫对独特的独特型表达的患者的骨髓瘤移植前后。重量份将接受一系列3次骨髓瘤Id-KLH（0.5 mg）s.c.与GM-CSF（250？g/mg 2）连续4天，随后进行自体外周单核干细胞移植。18分。在这项研究中得到了治疗。所有患者。已经证明了对KLH的应答，这表明BMT预处理方案产生的免疫抑制不是BMT后主动免疫的障碍。此外，50%的患者。已经证明了对独特型的T细胞应答，如通过体内细胞因子的自体独特型特异性产生和/或独特型特异性皮肤试验反应性所证明的。

Although high-dose chemoradiotherapy with autologous stem cell transplantation has shown some promise in the management of pts. with multiple myeloma, relapse of the underlying disease remains the primary cause of treatment failure. This is a pilot study to explore the possibility that active-specific immunotherapy may be effective in eliminating minimal residual disease remaining after high-dose therapy. Experimental studies in pts. with lymphoma have demonstrated the feasibility of immunoglobulin idiotype as a tumor-specific antigen for development of therapeutic vaccines against B-cell malignancies. Pts. will be immunized with myeloma idiotype protein, made immunogenic by conjugation to a carrier (KLH) and administration with GM-CSF as an immunological adjuvant, at several timepoints before and after high-dose therapy. The objective of this study is to test whether cellular and humoral immunity can be induced against the unique idiotype expressed on the patient's myeloma pre- and post-transplantation. Pts. will receive a series of 3 vaccinations with myeloma Id-KLH (0.5 mg) administered s.c. together with GM-CSF (250 ?g/mg2) for 4 consecutive days 2,3,and 6 months after high-dose therapy with either melphalan/TBI or melphalan/cytoxan followed by autologous peripheral mononuclear stem cell transplantation. 18 pts. have been treated on this study. All pts. have demonstrated responses to KLH, suggesting that immune suppression produced by the BMT conditioning regimen is not an obstacle to active immunization post-BMT. Furthermore, 50% of the pts. have demonstrated T-cell responses to idiotype, as demonstrated by autologous idiotype-specific production of cytokines and/or idiotype-specific skin test reactivity in vivo.