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Objectives: Modern management of myeloma has significantly improved survival, with increasing numbers of patients living beyond a decade. However, little is known about the long-term cardiovascular and respiratory status of intensively treated and multiply relapsed survivors., Methods: We performed detailed cardiovascular and respiratory evaluations in patients with intensively treated, advanced but stable myeloma. All patients had received at least two lines of treatment, including at least one haematopoietic stem cell transplantation procedure, but had stable, controlled disease and were off active treatment at the time of evaluation., Results: Thirty-two patients with a median duration of 6 years (range 2-12) from original diagnosis of myeloma and three lines (range 2-6) of treatment were evaluated. Despite normal physical examination in the majority, there was a high prevalence of sub-clinical cardiac and respiratory dysfunction, reflected by abnormalities of electrocardiography (45%), echocardiography (50%), serum N-terminal pro-B-type natriuretic peptide level (NT-pro-BNP, 50%), and pulmonary function testing (45%). NT-pro-BNP level correlated negatively with quality of life (P = 0.012) and positively with serum ferritin (P = 0.027). Dyspnoea score correlated with BMI (P = 0.001). Risk factors for cardiovascular disease (obesity, hypertension, hyperlipidaemia, and hyperinsulinaemia) were common., Discussion: Even in the absence of overt clinical features, the majority of intensively treated long-term survivors of myeloma have established cardiovascular and/or respiratory dysfunction, above levels expected in the general population of a similar age., Conclusion: This study supports routine screening and lifestyle modification combined with primary and secondary preventive strategies to reduce cardiovascular and respiratory disease and to preserve quality of life in transplanted myeloma patients.

Background: Pain is a common symptom in patients with multiple myeloma (MM). Many patients are dependent on analgesics and in particular opioids, but there is limited information on the impact of these drugs and their side effects on health-related quality of life (HRQoL)., Method: In a cross-sectional study, semi-structured interviews were performed in 21 patients attending the hospital with symptomatic MM on pain medications. HRQoL was measured using items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30., Results: Patients were able to recall a median of two (range 0-4) analgesics. They spontaneously identified a median of two (range 1-5) side effects attributable to their analgesic medications. Patients' assessment of HRQoL based on the EORTC QLQ-C30 questions 29/30 was mean 48.3 (95 % CI; 38.7-57.9) out of 100. Patients' assessment of their HRQoL in the hypothetical situation, in which they would not experience any side effects from analgesics, was significantly higher: 62.6 (53.5-71.7) (t test, p = 0.001)., Conclusion: This study provides, for the first time, evidence that side effects of analgesics are common in symptomatic MM and may result in a statistically and clinically significant reduction of self-reported HRQoL.

Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN) can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI) to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN) with those from healthy volunteers (HV). Twenty-four participants (n = 12 MM-CIPN, n = 12 HV) underwent Blood Oxygen Level-Dependent (BOLD) fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected). Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected). Significant positive correlation existed between the total neuropathy score (reduced version) and activation in the frontal operculum (close to insular cortex) during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87). Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

Context: The cumulative impact of disease and treatment-related factors on health-related quality of life (HRQoL) in long-term survivors of multiple myeloma is poorly characterized., Objectives: To characterize HRQoL and symptom burden in advanced, intensively treated myeloma., Methods: We performed detailed assessments in patients who had undergone hematopoietic stem cell transplantation and subsequent treatment for at least one episode of progressive disease. To exclude the impact of active disease and acute toxicity of treatment, patients were in a stable plateau phase. Patients were assessed for HRQoL (Short Form-12, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and Multiple Myeloma Module), pain (Brief Pain Inventory-Short Form), peripheral neuropathy (self-report Leeds Assessment of Neuropathic Symptoms and Signs), and concerns (adapted from Profile of Concerns). Serum interleukin-6 and tumor necrosis factor-alpha were measured., Results: A total of 32 patients were enrolled, with a median age of 55 years at diagnosis and 60 years at assessment. After a median 5.5 years from diagnosis and three lines of treatment, physical functioning was significantly compromised (P<0.001) and associated with progressive work disability and concerns regarding loss of independence. Fatigue and pain were the predominant symptoms, impacting negatively on physical functioning (P<0.001). Pain was predominantly neuropathic in half the patients. Serum interleukin-6 levels positively correlated with pain (P=0.03), pain interference (P=0.003), insomnia (P=0.02), and appetite loss (P=0.02), and inversely correlated with physical functioning (P=0.03)., Conclusion: Despite disease control and supportive care, intensively treated long-term myeloma survivors have significantly compromised HRQoL related to symptom burden. Systematic assessment is routinely indicated in advanced phase myeloma, even when disease activity is stable. Further studies should investigate the utility of interventional strategies and the relationship of cytokines with symptoms., (Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)