Barlogie Bart, Tricot Guido J, van Rhee Frits, Angtuaco Edguardo, Walker Ron, Epstein Joshua, Shaughnessy John D, Jagannath Sundar, Bolejack Vanessa, Gurley Jennifer, Hoering Antje, Vesole David, Desikan Raman, Siegel David, Mehta Jayesh, Singhal Seema, Munshi Nikhil C, Dhodapkar Madhav, Jenkins Bonnie, Attal Michel, Harousseau Jean-Luc, Crowley John
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Br J Haematol. 2006 Oct;135(2):158-64. doi: 10.1111/j.1365-2141.2006.06271.x. Epub 2006 Aug 25.
Total Therapy 1, the first tandem autotransplant trial for newly diagnosed patients with multiple myeloma, was designed to increase the frequency of complete response (CR) and thereby extend survival. With a median follow-up of 12 years, 62 of 231 initially enrolled patients are alive (17% at 15 years); 31 remain event free (7% at 15 years) including 16 of 94 (41%) that initially achieved CR. Currently alive patients less frequently had cytogenetic abnormalities (CAs) at baseline (P = 0.002), postenrolment (P < 0.001) and at relapse (P = 0.004); elevations of serum C-reactive protein (CRP) (P = 0.003) and lactate dehydrogenase (P = 0.029), anaemia (P = 0.029) and they more often completed two transplants within 12 months (P = 0.019). Postenrolment overall survival (OS) and event-free survival (EFS) were superior in the absence of CA of the hypodiploidy or deletion 13 variety (P < 0.001 and 0.037 respectively) and in the presence of low CRP at baseline (P = 0.001 and 0.017 respectively). Postrelapse survival was longer in the absence of CA at relapse (P < 0.001), IgA isotype (P = 0.002), International Staging System stage 3 (P = 0.014), and when patients had two protocol transplants prior to relapse (P = 0.038). Ten-year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high-dose melphalan, were applied together upfront for the management of myeloma.
“全程治疗1号”是针对新诊断的多发性骨髓瘤患者开展的首个串联自体移植试验，旨在提高完全缓解（CR）率，从而延长生存期。中位随访12年时，最初入组的231例患者中有62例存活（15年时为17%）；31例无事件发生（15年时为7%），其中94例最初达到CR的患者中有16例（41%）。目前存活的患者在基线时（P = 0.002）、入组后（P < 0.001）和复发时（P = 0.004）细胞遗传学异常（CA）的发生率较低；血清C反应蛋白（CRP）升高（P = 0.003）、乳酸脱氢酶升高（P = 0.029）、贫血（P = 0.029），且他们更常在12个月内完成两次移植（P = 0.019）。入组后，在不存在亚二倍体或13号染色体缺失类型的CA时（分别为P < 0.001和0.037）以及基线时CRP水平较低时（分别为P = 0.001和0.017），总生存期（OS）和无事件生存期（EFS）更佳。复发时不存在CA（P < 0.001）、IgA亚型（P = 0.002）、国际分期系统3期（P = 0.014）以及患者在复发前接受两次方案规定的移植时（P = 0.038），复发后的生存期更长。当将1989年可用的所有药物（尤其是大剂量美法仑）一起预先用于骨髓瘤治疗时，分别有15%和33%的患者可以实现10年EFS和OS。
