Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.

In diffuse large B-cell lymphoma (DLBCL), previous studies have suggested that, while concordant bone marrow (BM) involvement confers a poor prognosis, discordant BM involvement does not. Whether this correlation is independent of the non-Hodgkin lymphoma International Prognostic Index (IPI) was previously unknown. We reviewed all DLBCL case histories from 1986 to 1997 at our center with complete staging, IPI data, and follow-up. A total of 55 (11.2%) of 489 patients had BM involvement, including 29 with concordant involvement and 26 with discordant involvement. The 55 patients with BM involvement had a poor prognosis compared with the uninvolved BM group (5-year overall survival [OS], 34.5% versus 46.9%; log-rank P ‫؍‬ .019). However, concordant involvement portended a very poor prognosis (5-year OS, 10.3%; P < .001), whereas discordant involvement did not (5-year OS, 61.5%, P value nonsignificant). Compared with the discordant subset, the concordant subset patients were older, had a higher serum lactate dehydrogenase level, and a significantly higher IPI. However, the poor survival associated with concordant BM involvement was independent of the IPI score (P ‫؍‬ .002, Cox regression). We conclude that in patients with DLBCL, concordant but not discordant BM involvement confers a very poor clinical outcome. Furthermore, concordant BM involvement is an independent adverse prognostic factor. (Blood. 2007; 110:1278-1282)

• Thalidomide and prednisone maintenance after transplantation improves progressionfree but not overall survival.We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m 2 . The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival, progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio ‫؍‬ 0.77; P ‫؍‬ .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio ‫؍‬ 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P ‫؍‬ .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomideprednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit. (Blood. 2013;121(9):1517-1523)