KEYNOTE ADDRESS The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement MA Hussein 1 , FD Vrionis 2 , R Allison 3 , J Berenson 4 , S Berven 5 , E Erdem 6 , S Giralt 7 , S Jagannath 8 , RA Kyle 9 , S LeGrand 10 , R Pflugmacher 11 , N Raje 12 , SV Rajkumar 9 , L Randall 13 , D Roodman 14 , D Siegel 15 , R Vescio 16 , J Zonder 17 and BGM Durie 16 on behalf of the International Myeloma Working Group 18 1 Department of Hematologic Malignancies, H Lee Moffitt Cancer Center, Tampa, FL, USA; 2 Department of Neuro-Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USA; 3 Department of Radiation Oncology, Brody School of Medicine at ECU, Greenville, NC, USA; 4 Department of Hematology/Medical Oncology, Institute for Myeloma & Bone Cancer Research, Los Angeles, CA, USA; 5 Department of Orthopaedic Surgery, University of California, San Francisco, CA, USA; 6 Division of Radiology, Section of Interventional Neuroradiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; ; 7 Stem Cell Transplantation & Cellular Therapy Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 8 Department of Medical Oncology/Internal Medicine, St Vincent’s Comprehensive Cancer Center, New York, NY, USA; 9 Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, USA; 10 Department of Medical Oncology/Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA; 11 Department of Musculature, Charite ´ der Humboldt Universita `t, Berlin, Germany; 12 Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 13 Department of Orthopaedics, Huntsman Cancer Institute, Salt Lake City, UT, USA; ; 14 Department of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 15 Department of Medical Oncology, Hackensack Cancer Center, Hackensack, NJ, USA; 16 Department of Hematology/Oncology, Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA, USA and 17 Department of Medicine, Division of Hematology-Oncology, Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, MI, USA Leukemia advance online publication, 29 May 2008; doi:10.1038/leu.2008.127 Introduction There are approximately 20 000 new patients diagnosed with myeloma in the United States each year. 1 With the availability of better treatments and resultant improved survival, there are currently close to 100 000 patients living with myeloma in the United States. Similar incidence and prevalence rates exist throughout Europe. 2 Of these patients, the spine is affected by osteolytic and/or osteopenic bone disease in 70%. 3 Myeloma is the commonest primary cancer affecting the spine. Painful vertebral compression fractures (VCFs) affect approximately 30% of myeloma patients. As myeloma patients live longer, it is especially relevant to provide the best available treatment for pain and reduce disabilities that can result from VCFs. 4 The focus of this summary is to assess the role of minimally invasive percutaneous injection of polymethyl methacrylate (PMMA), first developed as ‘vertebroplasty’ in France in the late 1980s. Considerable experience accrued, especially in Europe, with the use of vertebroplasty as treatment for painful VCFs. The fractured bone fragments are stabilized and strengthened by PMMA and pain is substantially improved. A more recent modification of vertebroplasty is percutaneous balloon kypho- plasty whereby inflation of a balloon prior to PMMA injection can restore vertebral height and reduce kyphotic deformity in addition to stabilizing the fractured vertebral body. The first prospective trial evaluating the role of balloon kyphoplasty in multiple myeloma showed that over 80% of the treated patients experienced significant pain control. 5 In addition, there was an overall 30% height restoration with improvement of 60–70% of height restoration when the procedure was performed for fractures less than 6 months old. 5 The procedure was also noted to be effective and safe in other malignancies. 6 In another study of 20 multiple myeloma patients (48 levels) treated with balloon kyphoplasty, significant pain improvement as judged by visual analogue scale occurred within the first year of follow-up. 7 About 80% of patients with initial kyphotic deformity had post-operative kyphosis correc- tion of approximately 61, with only minimal loss of height after 1 year (B1.81). The overall data related to both vertebroplasty and balloon kyphoplasty are addressed in a number of publications. 5,8–20 In considering the potential benefit of PMMA injection, it is necessary to be aware of the biomechanics of pathologic spine fractures (Figure 1). With the occurrence of a VCF, the center of gravity moves forward. Because of the large bending moment created, the anterior spine, especially in the regions adjacent to the VCF, must resist larger compressive stresses. The posterior muscles and ligaments are additionally stressed, which can be an obvious source of pain. Early intervention is a way to reduce the risk of a ‘domino effect’ with increased forward movement of the center of gravity, additional compressive stresses and possible further VCFs. The consequences of progressively altered vertebral mechanics and the kyphosis-related VCFs in myeloma patients can be substantial as summarized in Table 1. Obviously, the safety of vertebral augmentation is an important consideration. The potential complications of vertebral augmentation are summarized in Table 2. A literature review meta-analysis of procedure-related complications for balloon kyphoplasty and vertebroplasty indicates that complications such as extravasation of PMMA are less with balloon kypho- plasty. 21 It should be noted that asymptomatic extravasation of Received 18 February 2008; revised 2 April 2008; accepted 28 April 2008 Correspondence: Dr BGM Durie, Aptium Oncology Inc., Cedars-Sinai Outpatient Cancer Center, 8201 Beverly Boulevard, Los Angeles, CA 90048, USA. E-mail: bdurie@aptiumoncology.com or Dr MA Hussein, H Lee Moffitt Cancer & Research Institute 12902 Magnolia Drive, SRB4, Tampa, FL 33612, USA. Email: mohamad.hussein@moffitt.org 18 See Appendix for members of the International Myeloma Working Group Leukemia (2008), 1–6 & 2008 Nature Publishing Group All rights reserved 0887-6924/08 $30.00 www.nature.com/leu