Teste citogenético por Hibridização in Situ por Fluorescência (FISH) para detecção de alterações citogenéticas de alto risco em pacientes com mieloma múltiplo / Cytogenetic test by Hybridization in Situ by Fluorescence (FISH) for detection of alterations High-risk cytogenetics in patients with multiple myeloma

INTRODUÇÃO: O mieloma múltiplo é uma neoplasia dos plasmócitos. Essas células neoplásicas proliferam na medula óssea impedindo o funcionamento das demais células hematológicas. As células neoplásicas produzem uma imunoglobulina monoclonal (proteína M) que é importante na fisiopatologia e no diagnóstico dessa doença. O mieloma múltiplo geralmente acomete adultos acima de 60 anos e estima-se que no Brasil a sua incidência anual esteja próximo à 1,2 indivíduos para cada 100.000 habitantes, com elevada letalidade. As manifestações clínicas mais comuns são dores ósseas, anemia e infecções recorrentes. As alterações mais comuns em exames de imagem e de laboratório incluem lesões líticas nos ossos, exames associados com insuficiência renal, hipercalcemia e anemia, além do achado da proteína M. Determinadas alterações citogenéticas estão associadas com o tratamento que deve ser instituído para o paciente e com o seu prognóstico. As alterações cromossômicas estudadas foram: t(4;14), del(17p13) e t(14;16). TECNOLOGIA: Citogenética por Hibridização in Situ por Fluorescência (FISH). PERGUNTA: Deve-se utilizar a citogenética por Hibridização In Situ por Fluorescência (FISH) versus citogenética convencional para detectar as alterações t(4:14), del(17p13) e t(14:16) em pacientes com mieloma múltiplo? EVIDÊNCIAS CLÍNICAS: Foi realizada busca de estudos que avaliassem a tecnologia nas bases de dados Embase, Medline (via Pubmed), Cochrane Library e LILACS. Após a triagem de 1346 relatos, 11 estudos observacionais foram selecionados. Nos domínios do QUADAS-2, a maioria dos estudos apresentou risco de viés incerto, exceto para o domínio Fluxo e Temporalidade, em que 81,8% dos estudos apresentaram baixo risco de viés. Os estudos incluídos analisaram uma amostra de 781 pacientes com mieloma múltiplo. Destes, 653 foram avaliadas pelo FISH e 719 pela citogenética convencional. A t(4;14) foi detectada em 11,3% (58/518) das amostras por FISH e 0,17% (1/607) por citogenética convencional. Os resultados da meta-análise mostraram que o FISH aumentou em 12% a detecção da t(4;14) quando comparado a citogenética convencional (RD: 0,12 [IC 95%: 0,06-0,19]; p < 0,0001; I2 : 52%). Em relação à del(17p13), esta foi detectada em 12,2% (80/653) das amostras por FISH e 1,6% (10/607) por citogenética convencional. O FISH aumentou em 12% a detecção da del(17p13) em comparação à citogenética convencional (RD: 0,12 [IC 95%: 0,04-0,20]; p < 0,0001; I 2 : 77%). Por fim, a t(14;16) foi detectada em 0,42% (2/478) das amostras por FISH e 0,17% (1/607) por citogenética convencional. Não houve diferença entre o FISH e a citogenética convencional para detecção da t(14;16) (RD: 0,00 [IC 95%: -0,01-0,02]; p = 0,41; I2 : 0%). A qualidade da evidência, avaliada pelo GRADE, foi considerada muito baixa para todos os desfechos avaliados. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Foram elaborados dois cenários, proposto e alternativo, considerando as estratégias de estadiamento incluindo FISH e citogenética convencional, variando a porcentagem de pacientes submetidos ao teste citogenético por FISH. A incorporação do FISH para o estadiamento dos pacientes com mieloma múltiplo pode provocar um incremento orçamentário em R$239.206,38 para o primeiro ano (2022), atingindo R$1.246.915,77 no quinto ano (2026), quando inicialmente 5% dos pacientes são submetidos ao FISH e ocorre aumento progressivo de 5% ao ano. O impacto em cinco anos seria de R$ 3.691.966,50. Quando inicialmente 10% dos pacientes diagnosticados com mieloma múltiplo são estadiados por meio do FISH, com o aumento progressivo de 10% ao ano, mantendo-se porcentagem constante para a citogenética convencional, o impacto orçamentário incremental seria de R$478.412,76 para o primeiro ano (2022), atingindo R$2.493.831,54 no quinto ano de incorporação (2026), sendo o valor acumulado em cinco anos de R$ 7.383.933,00. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: As pesquisas nas bases de dados para monitoramento do horizonte tecnológico identificaram três modelos de sonda para o painel FISH em pacientes com mieloma múltiplo no FDA. No Clinical Trials nenhuma nova tecnologia para avaliação citogenética foi identificada. Em relação ao depósito de patentes, foi encontrado um depósito patentário chinês do ano de 2019. PERSPECTIVA DO PACIENTE: Foi aberta chamada pública conjunta para Perspectiva do Paciente durante o período de 18/10/2021 a 24/10/2021, que contou com quinze inscrições, sendo o representante definido por consenso do grupo. No relato, o participante descreveu aspectos da sua vivência como paciente com mieloma múltiplo, destacando a rapidez na obtenção de diagnóstico, a realização do transplante de medula óssea e o uso de diferentes tecnologias durante o tratamento.  Além disso, informou ter tido boa resposta terapêutica à lenalidomida durante cinco anos, em virtude da progressão da doença depois desse intervalo temporal, passou a utilizar protocolo com daratumumabe, apresentando melhora geral do quadro clínico. CONSIDERAÇÕES FINAIS: O teste FISH já é realizado pelo Sistema Único de Saúde (SUS) no diagnóstico de outras doenças. Neste Relatório, foi analisado a ampliação de uso deste exame para o diagnóstico de mieloma múltiplo. Pelos achados desta revisão, o teste FISH foi superior à citogenética convencional no diagnóstico das alterações citogenéticas t(4;14) e del(17p13), que são alterações relativamente frequentes e relevantes para o tratamento e o prognóstico dos pacientes com esse tipo de câncer. A alteração t(14;16), por ter baixa prevalência nos pacientes com esse tipo de câncer, demanda que ela seja analisada em uma amostra maior de indivíduos para que seja evidenciada uma diferença significativa entre os dois métodos. No Brasil, os laboratórios de referência para doenças raras possuem a infraestrutura necessária para a realização dos exames e seria necessária a ampliação do uso por meio do SUS. Do ponto de vista da implementação, a capacitação de recursos humanos é um fator de extrema importância, uma vez que a maioria destes laboratórios, atualmente, não possui pessoal capacitado especificamente para analisar amostras de pacientes com mieloma múltiplo. As agências internacionais NICE e CADTH recomendam a realização do FISH como parte dos exames diagnósticos necessários para o estadiamento citogenético e a tomada de decisão quanto a estratégia terapêutica a ser empregada diante da classificação de risco dos pacientes com mieloma múltiplo. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Plenário presentes na 104ª Reunião da Conitec, no dia 08 de dezembro de 2021, deliberaram, por unanimidade, sem nenhum conflito de interesses, que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à ampliação de uso do teste citogenético por Hibridização in Situ por Fluorescência (FISH) na detecção de alterações citogenéticas de alto risco em pacientes com mieloma múltiplo. CONSULTA PÚBLICA: Por meio da Consulta Pública nº 116/2021, realizada entre os dias 27/12/2021 e 17/01/2022, foram recebidas 73 contribuições, todas favoráveis à ampliação do uso do FISH para detecção de alterações moleculares de alto risco em pacientes com mieloma múltiplo. As evidências científicas apresentadas reforçaram a importância do FISH enquanto método de identificação destas alterações moleculares, para as quais a citogenética convencional possui baixa sensibilidade. Na avaliação econômica e de impacto orçamentário, foram apontadas possibilidades de redução do custo do exame com a utilização de menor número de sondas de hibridização, dependendo do nível de treinamento dos profissionais. Pacientes e associações enfatizaram a necessidade de garantir o acesso ao exame pelo SUS e, como pontos negativos, o alto custo do exame na rede privada e a indisponibilidade atual do exame no sistema público de saúde. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário presentes na 105ª Reunião da Conitec, no dia 09/02/2022, deliberaram, por unanimidade, sem nenhuma declaração de conflito de interesses, recomendar a ampliação de uso do teste citogenético por Hibridização in Situ por Fluorescência (FISH) na detecção de alterações citogenéticas de alto risco em pacientes com mieloma múltiplo. Foi assinado o Registro de Deliberação nº 695/2022. DECISÃO: Ampliar o uso do teste citogenético por Hibridização in Situ por Fluorescência (FISH) na detecção de alterações citogenéticas de alto risco em pacientes com mieloma múltiplo, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 20, publicada no Diário Oficial da União nº 49, seção 1, página 95, em 14 de março de 2022.

A budget impact analysis of lenalidomide in multiple myeloma Egyptian patients.

INTRODUCTION: The aim of this study was to estimate the budget impact of lenalidomide and dexamethasone (RD) versus bortezomib, cyclophosphamide and dexamethasone (VCD) in newly diagnosed multiple myeloma (NDMM) and relapsed refractory (RR) MM patients, from the perspective of the Egyptian Ministry of health (MoH). METHODS: Two budget impact dynamic models were conducted to assess the budget impact of RD entry over a 3-year period. The clinical data for the modeled cohorts were based on published articles. Total annual medical costs associated with non-progression and progression disease states included the sum of estimated costs for adverse effects management, concomitant treatments, hospitalization and the follow up were measured. Deterministic sensitivity analyses were performed. RESULTS: The target population in a given year was estimated to include 245 patients with RRMM and 291 patients with NDMM receiving RD versus VCD. In RRMM, the annual budget savings of lenalidomide entry were estimated at EGP -1,103,969, -3,362,793 and -5,949,228 at year 1, year 2 and year 3, respectively. In NDMM, the annual budget savings of lenalidomide entry were estimated at EGP869,415, -1,779,776 and -2,139,311 at year 1, year 2 and year 3, respectively, to the payer after lenalidomide entry. The model results in RRMM were most sensitive to variations in patients eligible to transplantation in RRMM. In NDMM, the model results were most sensitive to the market share of VCD in the first year. CONCLUSION: The results of our BI models suggest that not only does RD treatment have an effect on the budget, but also has major cost savings in other areas which are very important while considering the total costs of MM treatment. This study results provided evidence-based information to the MoH that will help in decision making of whether to implement RD as a treatment intervention or not.

Geriatric Assessment and Frailty Scores Predict Mortality in Myeloma: Systematic Review and Meta-analysis.

The incidence of multiple myeloma is increasing as the proportion of older adults is growing rapidly. A critical evaluation of the evidence available is needed to guide the management of older patients with myeloma. A systematic review was conducted to report the prognostic value of geriatric assessment and frailty scores in older patients with multiple myeloma. We conducted a literature search in February and August 2018. Two researchers extracted the data and assessed the quality of the studies. Geriatric assessment and frailty scores were defined as those evaluating at least 2 geriatric domains. Main outcomes were mortality or toxicity. We estimated the pooled hazard ratios (HR) with 95% confidence intervals (CIs) using a random-effects model. We screened titles and abstracts of 1672 citations for eligibility. Seven studies were included in the qualitative analysis, of which 3 were included in the meta-analysis. Two studies reported similar risks of hematologic adverse events in intermediate-fit and in frail patients compared to frail, but a significantly increased risk of nonhematologic adverse events in frail patients compared to fit patients. In meta-analysis, a significantly increased HR for death was observed in patients with activity of daily living score ≤ 4 (pooled HR = 1.576; 95% CI, 1.051-2.102; χ2 = 0.87; P = .647; I2 = 0). Patients classified as frail showed higher risk of death than fit patients (pooled HR = 2.169; 95% CI, 1.002-2.336; χ2 = 3.02; P = .221; I2 = 33.7%). GA and frailty score are effective in predicting mortality in older adults with myeloma.

Comprehensive geriatric assessment and decision-making in older men with incurable but manageable (chronic) cancer.

PURPOSE: In older cancer patients, treatment decision-making is often complex. A comprehensive geriatric assessment (CGA) is an established tool used in geriatric medicine to identify unmet need requiring intervention. This study aimed to assess whether using a CGA in older male cancer patients with incurable but manageable disease provides information that would alter a cancer clinician's intended management plan. Acceptability and feasibility were secondary aims. METHODS: Elderly men with incurable but manageable malignancies (advanced prostate cancer and multiple myeloma) who had previously received at least one line of treatment were recruited from hospital outpatient clinics. A CGA was undertaken. Additional parameters measuring pain, fatigue and disease-specific concerns were also recorded, at the recommendation of patient involvement groups. Results were made available to clinicians. Patient and clinician acceptability and changes in subsequent management were recorded. RESULTS: Forty-eight patients completed the study. The median ages were 70.8 years and 74 years for myeloma and prostate respectively. Most identified concerns are related to disease-specific concerns (93%), pain (91%), frailty (57%) and nutrition (52%). Results altered the clinician's oncological management plan in nine cases only. Patients found the format and content of CGA acceptable. CONCLUSIONS: Many unmet needs were identified in this population of elderly men with manageable but non curable cancer which led to supportive care referrals and interventions. The CGA, however, did not result in significant changes in clinical oncology treatment plans for the majority of patients. The application of the CGA and other assessments was viewed positively by participants and can feasibly be undertaken in the outpatient oncology setting.

Disease and Symptom Care: A Focus on Specific Needs of Patients With Multiple Myeloma.

Patients with multiple myeloma (MM) often deal with short- and long-term side effects of the treatment and disease sequelae. Reasons for inadequately managed symptoms are multifactorial (e.g., the patient may fear treatment interruption, the clinician does not assess or address the symptoms) and can affect patients' ability to remain on the recommended treatment. This article provides background surrounding this supplement's development and describes the importance of symptom assessment and management.
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Heart and Lung Complications: Assessment and Prevention of Venous Thromboembolism and Cardiovascular Disease in Patients With Multiple Myeloma
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BACKGROUND: Venous thromboembolism (VTE) and cardiovascular (CV) disease can occur in patients with multiple myeloma. Although VTE and CV disease are separate medical conditions, they can be serious and even life-threatening.
. OBJECTIVES: The objectives of this article are to describe risk factors for cancer-associated VTE, describe the influence of CV disease on patients with multiple myeloma, and review the approaches to VTE and CV disease identification and treatment.
. METHODS: PubMed and CINAHL® databases were used to identify literature to describe VTE and CV in patients diagnosed with multiple myeloma.
. FINDINGS: When present in patients with multiple myeloma, VTE and CV disease can limit patient tolerance for myeloma treatment and, therefore, decrease therapeutic options.

Is Early Palliative Care Feasible in Patients With Multiple Myeloma?

CONTEXT: Evidence for the benefits of early palliative care (EPC) in patients with solid tumors is strong, but EPC has received scant attention in hematologic malignancies. OBJECTIVE: To assess the benefits of outpatient-based EPC for symptom control in patients with multiple myeloma. METHODS: Retrospective study of patients attending the Multiple Myeloma Palliative Care Clinic at our hospital in the year 2013 (February 1-December 31). The following symptoms were assessed at baseline and at three follow-up consultations using a Numerical Visual Scale (0 = no symptoms; 10 = worst possible): pain, anorexia, constipation, insomnia, nausea/vomiting, dyspnea, anxiety, and sadness. Physical and emotional symptom burden scores were calculated. Pain interference with general activity, sleep, and mood was also evaluated. RESULTS: About 67 patients were included. The proportion of patients reporting moderate-to-severe pain (Numerical Visual Scale ≥5) decreased significantly from baseline to the final follow-up: worst pain decreased from 57% to 18% (P < 0.0001), whereas average pain fell from 24% to 2% (P < 0.0001). The percentage of patients reporting no pain interference increased significantly from baseline: general activity (52% vs. 82%; P = 0.0001), sleep (73% vs. 91%; P = 0.01), and mood (52% vs. 87.5%; P = 0.0001). Physical and emotional symptom burden also improved, with significantly fewer patients reporting depression (13% vs. 5%; P = 0.001). Most patients (86.6%) were alive and still attending the Multiple Myeloma Palliative Care Clinic at study end. CONCLUSIONS: These findings indicate that EPC is feasible in patients with multiple myeloma. Pain and other symptoms were well controlled.

Geriatric Assessment to Predict Survival and Risk of Serious Adverse Events in Elderly Newly Diagnosed Multiple Myeloma Patients: A Multicenter Study in China.

BACKGROUND: Elderly multiple myeloma (MM) patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival (OS) time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM. METHODS: We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects. RESULTS: An additive scoring system (range: 0-5), based on age, Katz's Activity of Daily Living (ADL) and Lawton's Instrumental Activity of Daily Living (IADL) ≤5 and Charlson Comorbidity Index (CCI) was developed to identify three groups: fit (score = 0); intermediate-fitness (score = 1); and frail (score ≥2). The 3-year OS was 63% in fit patients, 63% in intermediate-fitness patients, and 49% in frail patients ≥3 hematologic adverse events (AEs) were documented in 45 (35.4%) fit, 34 (34%) intermediate-fitness, and 121 (30.2%) frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness (hazard ratios [HR]: 0.99, 95% confidence interval [CI]: 0.54-1.47, P = 1.000) and in frail patients (HR: 1.16, 95% CI: 0.70-1.93, P = 0.558) compared with fit ones. CONCLUSIONS: MM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in frailty with International Staging System (ISS) II/III was the worst in all patients.

Assessment of Bone Fragility in Patients With Multiple Myeloma Using QCT-Based Finite Element Modeling.

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)-based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T12 (T11 if T12 was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (-15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (-21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (-27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R2 = 0.57, yield force: R2 = 0.59, work to yield: R2 = 0.50, p < 0.001), BV/TV (stiffness: R2 = 0.56, yield force: R2 = 0.58, work to yield: R2 = 0.49, p < 0.001), and Tb.Sp (stiffness: R2 = 0.51, yield force: R2 = 0.53, work to yield: R2 = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. © 2016 American Society for Bone and Mineral Research.

Therapeutic Efficacy and Cost Effectiveness of High Cut-Off Dialyzers Compared to Conventional Dialysis in Patients with Cast Nephropathy.

BACKGROUND: High Cut-Off (HCO) dialysis membranes efficiently reduce serum free light chain (FLC) concentrations and may improve renal recovery and survival from multiple myeloma (MM) associated renal failure with cast nephropathy. However, clinical trials comparing dialysis with HCO versus conventional filters are lacking. The aim of this study was to assess clinical outcomes and economic impact of HCO dialyzers compared to conventional hemodialysis membranes in cast nephropathy. METHODS: Multicenter retrospective analysis of 19 patients treated for renal failure from FLC associated cast nephropathy with standard induction chemotherapy (bortezomib/dexamethasone). We compared hemodialysis treatment with High Cut-Off (n = 12) versus conventional dialyzers (n = 7). Primary endpoint was survival; secondary endpoints were renal recovery, renal function and treatment costs. RESULTS: At 12 months, patient survival was 25% in the HCO group versus 0% in controls (p = NS). A tendency towards faster renal recovery (p = 0.066) and better renal function at 3, 6 and 12 months (p = 0.109) after diagnosis of MM was noted in the HCO group. Complete renal response rate was achieved in 10.5 and 0% of HCO and control patients, respectively, partial renal response in 15.8 and 5.3%, and minor renal response in 26.3 and 15.8%, respectively. Both patient survival and renal recovery were significantly correlated with the extent of free light chain (FLC) reduction in serum. Median treatment costs were CHF 230'000 and 223'000 (p = NS) in the HCO and control group, respectively. CONCLUSIONS: Hemodialysis treatment with HCO membranes for cast nephropathy tended towards better survival as well as faster and better recovery of renal function versus conventional dialyzers. Moreover, total medical costs were comparable between groups. In the absence of results from randomized prospective trials on this topic, the use of HCO dialyzers in patients with renal failure from cast nephropathy may be recommended. Prospective randomized trials are required.

Autologous stem cell transplantation improves quality of life in economically challenged, Brazilian multiple myeloma patients.

OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in São Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post-treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS: Of the included patients, 87.8% had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t-tests confirmed a better outcome after autologous stem cell transplantation CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell transplantation in the quality of life of multiple myeloma patients in two public Brazilian institutions that provide assistance for economically challenged patients.

Routine health maintenance in patients living with multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

Patients diagnosed with multiple myeloma are living longer because of new therapeutic options. Helping patients with multiple myeloma maintain a good state of health from the time of diagnosis and throughout their therapy leads to better quality of life. However, patients with multiple myeloma are at risk for illnesses experienced by the general population and at additional risk for illnesses related to multiple myeloma and its treatment. Therefore, the International Myeloma Foundation Nurse Leadership Board (NLB) has developed practice recommendations to meet the particular needs of adult patients with multiple myeloma using evidence-based recommendations for screening and disease prevention, as well as nursing experience. The NLB recommendations are designed to address and overcome barriers to health maintenance by educating and empowering nurses and their patients.

Deriving a preference-based measure for cancer using the EORTC QLQ-C30.

OBJECTIVE: The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is one of the most commonly used measures in cancer care but in its current form cannot be used in economic evaluation because it does not incorporate preferences. We address this gap by estimating a preference-based measure for cancer from the EORTC QLQ-C30. METHODS: Factor analysis, Rasch analysis, and other psychometric analyses were undertaken on a clinical trial dataset of 655 patients with multiple myeloma to derive a health state classification system amenable to valuation. Second a valuation study was conducted of 350 members of the UK general population using time trade-off. Mean and individual-level multivariate regression models were fitted to derive preference weights for the classification system. RESULTS: The health state classification system has eight dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue and sleep disturbance, nausea, constipation, and diarrhea) with four or five levels each. Regression models have few inconsistencies (0 to 2) in estimated preference weights and small mean absolute error ranges (0.046 to 0.054). CONCLUSIONS: It is feasible to derive a preference-based measure from the EORTC QLQ-C30 for use in economic evaluation. Future research will extend this to other countries and replicate across other patient groups.

Responsiveness and minimal important score differences in quality-of-life questionnaires: a comparison of the EORTC QLQ-C30 cancer-specific questionnaire to the generic utility questionnaires EQ-5D and 15D in patients with multiple myeloma.

OBJECTIVES: The aims of this study were to (i) compare the responsiveness of the EORTC QLQ-C30 cancer-specific questionnaire and the generic questionnaires EQ-5D and 15D used for economic evaluation of healthcare interventions and (ii) determine the minimal important differences (MIDs) in these questionnaires. The MID is the smallest change in a quality-of-life score considered important to patients. METHODS: Between 2006 and 2008, 239 patients with multiple myeloma completed the questionnaires at inclusion (T1) and after 3 months (T2). At T2, patients were asked whether they had noticed any change in their quality of life. Responsiveness and MIDs were determined by mean score changes (T2-T1) for patients who, in the interview, stated they had improved, deteriorated, or were unchanged. Responsiveness was also assessed using standardized response means. Wilcoxon tests for pair differences were used to evaluate the statistical significance of the changes. RESULTS: Patients who improved had significantly (P < 0.01) higher scores at T2 in all three questionnaires. Patients who deteriorated reported lower scores at T2; however, for the 15D, the differences in score were not statistically significant. The MIDs for the QLQ-C30, EQ-5D, and 15D were 8, 0.08, and 0.03 in patients who improved and 12, 0.10 and 0.02 in patients who deteriorated, respectively. CONCLUSIONS: All three questionnaires showed an acceptable responsiveness in patients who improved. However, the 15D did not respond optimally in patients who deteriorate and cannot be recommended for use in patients with myeloma.

Platelet and red blood cell utilization and transfusion independence in umbilical cord blood and allogeneic peripheral blood hematopoietic cell transplants.

Allogeneic hematopoietic cell transplantation (HCT) recipients have substantial transfusion requirements. Factors associated with increased transfusions and the extent of blood product use in umbilical cord blood (UCB) recipients are uncertain. We reviewed blood product use in 229 consecutive adult recipients of allogeneic HCT at the University of Minnesota: 147 with leukemia, 82 lymphoma or myeloma; 58% received unrelated UCB and 43% sibling donor peripheral blood stem cell (PBSC) grafts. Although neutrophil recovery was prompt (UCB median 17, range: 2-45 days, and PBSC 14, range: 3-34 days), only 135 of 229 (59% cumulative incidence) achieved red blood cell (RBC) independence and 157 (69%) achieved platelet independence by 6 months. Time to platelet independence was prolonged in UCB recipients (median UCB 41 versus PBSC 14 days) and in patients who had received a prior transplant (median 48 versus 32 days). Patients who received UCB grafts required more RBC through day 60 post-HCT (mean UCB 7.8 (95% confidence interval [CI] 6.7-8.9) versus PBSC 5.2 (3.7-6.7) transfusions, P = .04), and more platelet transfusions (mean 25.2 (95% CI 22.1-28.2) versus 12.9 (9.4-16.4), P < .01) compared to PBSC recipients. Patients receiving myeloablative (MA) conditioning required more RBC and platelet transfusions during the first 2 months post-HCT compared to reduced-intensity conditioning (RIC) (7.4 versus 6.2, P = .30 for RBC; 23.2 versus 17.5, P = .07 for platelets). Despite prompt neutrophil engraftment, UCB recipients had delayed platelet recovery as well as more prolonged and costly blood product requirements. Enhanced approaches to accelerate multilineage engraftment could limit the transfusion-associated morbidity and costs accompanying UCB allotransplantation.

Unmet supportive care needs, psychological well-being and quality of life in patients living with multiple myeloma and their partners.

PURPOSE: The aim of this project was to identify the nature and range of needs, as well as levels of quality of life (QOL), of both patients living with myeloma and their partners. METHODS: A cross-sectional survey was used, recruiting patients and their partners from 4 hospitals in the United Kingdom at a mean time post-diagnosis of 5 years. Patients completed a scale exploring their Supportive Care Needs, the Hospital Anxiety and Depression Scale (HADS) and the EORTC QOL scale with its Myeloma module. The partners completed the partners' version of the Supportive Care Needs scale and HADS. RESULTS: A total of 132 patients and 93 of their partners participated. One-quarter of the patients and one-third of the partners reported unmet supportive care needs. About 27.4% of patients reported signs of anxiety and 25.2% reported signs of depression. Almost half the partners (48.8%) reported signs of anxiety and 13.6% signs of depression. Anxious/depressed patients had more than double unmet needs than non-anxious/depressed patients (P<0.05). QOL was moderate, with key areas of impairment being physical, emotional, social and cognitive functioning, and patients complained of several symptoms, including tiredness (40.7%), pain (35.9%), insomnia (32.3%), peripheral neuropathies (28.3%) and memory problems (22.3%). About 40.8% were worried about their health in the future. CONCLUSION: Long-term supportive care services should provide support to both patients and their partners in relation to their unmet needs, screening them for psychological disorders, referring them appropriately and timely, and optimising symptom management in order to improve the patients' QOL.

Autologous stem cell transplantation improves quality of life in economically challenged, brazilian multiple myeloma patients

OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in São Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post-treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS: Of the included patients, 87.8 percent had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t-tests confirmed a better outcome after autologous stem cell transplantation CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell transplantation in the quality of life of multiple myeloma patients in two public Brazilian institutions that provide assistance for economically challenged patients.

Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

OBJECTIVE: The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma. SUBJECTS AND METHODS: Twenty-four patients (13 women, 11 men; mean age, 67.1 years; range, 44-83 years) with bone marrow biopsy-proven multiple myeloma were included in the study. All patients underwent PET/CT and whole-body MRI within 10 days of each other. Eight patients underwent more than one follow-up PET/CT and whole-body MRI examination, for a total of 34 pairs of images. Activity was defined as lesions with a maximum standardized uptake value greater than 2.5 at PET and as evidence of marrow packing at whole-body MRI. PET and whole-body MRI results were correlated with findings at bone marrow aspiration biopsy. RESULTS: PET had a sensitivity of 59%, specificity of 75%, positive predictive value of 81%, and negative predictive value of 50% (p = 0.08). Whole-body MRI had a sensitivity of 68%, specificity of 83%, positive predictive value of 88%, and negative predictive value of 59% (p = 0.01). In 62% of cases, PET and whole-body MRI findings were concordant. When PET and whole-body MRI findings were concordant and positive, no false-positive results were found, yielding a specificity and a positive predictive value of 100% (p = 0.04). CONCLUSION: Whole-body MRI performed better than PET in the assessment of disease activity, having a higher sensitivity and specificity. The positive predictive value of whole-body MRI in the assessment of active disease was high at 88%. When used in combination and with concordant findings, PET and whole-body MRI were found to have a specificity and positive predictive value of 100%, which may be of value to clinicians assessing the effectiveness of aggressive and expensive treatment regimens.

Myeloma bone disease: pathogenetic mechanisms and clinical assessment.

Bone disease in multiple myeloma (MM) leads to progressive devastation of the skeleton and is the most severe cause of morbidity. Its pathogenetic mechanisms are not fully defined, though the current evidence points to hyperactivation of osteoclasts (OC) in presence of a major defect of bone repairing in erosion sites due to osteoblast (OB) impairment. Bone resorption, however, is promoted by early OB, namely stromal cells that respond to chronic stimulation by myeloma cells by enhancing marrow levels of RANKL and other osteoclastogenic factors and thus accelerating the maturation of OC progenitors. In myeloma bone disease (MBD), OBs are systematically defeated by a number of inhibiting effects induced by the malignant clone within the marrow microenvironment. Thus, MBD primarily affects the OB lineage, particularly in overt MM, where serum markers of osteoblastogenesis, such as osteocalcin and osteoprotegerin, are extremely low in contrast with their slight increase in inactive MM. These markers, in association with others of bone turnover (RANKL, MIP-1alpha, type I collagen telopeptides such as NTX and CTX) may be used in the clinical assessment of MBD as well as to monitor the efficacy of bisphosphonate in delaying the progressive skeletal destruction.