RESUMO
BACKGROUND: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments. METHODS: Patients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression. RESULTS: Minimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with ≥3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4-2.3 months). Minimal malignant plasma cells detection limit was 4 × 10-5. CONCLUSIONS: Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression. TRIAL REGISTRATION: NCT01208766.
Assuntos
Citometria de Fluxo/estatística & dados numéricos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Neoplasia Residual/diagnóstico , Neoplasia Residual/mortalidade , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Países Escandinavos e Nórdicos , Sensibilidade e Especificidade , Suspensão de Tratamento , Adulto JovemRESUMO
OBJECTIVE: We investigated the efficacy and safety of carfilzomib-containing induction before salvage high-dose melphalan with autologous stem-cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma. METHODS: This randomised, open-label, phase 2 trial included patients with first relapse of multiple myeloma after upfront ASCT who were re-induced with four cycles of carfilzomib, cyclophosphamide and dexamethasone. Two months after salvage, ASCT patients were randomised to either observation or maintenance therapy with iv carfilzomib 27 â 56 mg/sqm and p.o. dexamethasone 20 mg every second week. The study enrolled 200 patients of which 168 were randomised to either maintenance with carfilzomib and dexamethasone (n = 82) or observation (n = 86). RESULTS: Median time to progression (TTP) after randomisation was 25.1 months (22.5-NR) in the carfilzomib-dexamethasone maintenance group and 16.7 months (14.4-21.8) in the control group (HR 0.46, 95% CI 0.30-0.71; P = .0004). The most common adverse events during maintenance were thrombocytopenia, anaemia, hypertension, dyspnoea and bacterial infections. CONCLUSION: In summary, maintenance therapy with carfilzomib and dexamethasone after salvage ASCT prolonged TTP with 8 months. The maintenance treatment was in general well-tolerated with manageable toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Tomada de Decisão Clínica , Dexametasona/administração & dosagem , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Oligopeptídeos/administração & dosagem , Prognóstico , Transplante Autólogo , Resultado do TratamentoRESUMO
Monoclonal gammopathy is a frequent finding and may be associated with severe cancer such as myelomatosis and other B-cell lymphoproliferative disorders. However, the monoclonal component can also be the direct cause of serious disease, namely monoclonal gammopathy of clinical significance (MGCS). MGCS is most likely significantly underdiagnosed and is consequently also undertreated. In order to achieve a good therapeutic outcome, it is crucial that the condition is recognised at an early stage, so that treatment can be initiated before the patient has developed irreversible organ damage. Increased awareness of MCGS is therefore essential.
Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , HumanosRESUMO
The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study (NCT02181413) demonstrated improved progression-free survival with ixazomib maintenance versus placebo post autologous stem cell transplant (ASCT) in multiple myeloma patients. We report additional safety data from TOURMALINE-MM3 to inform adverse event (AE) management recommendations. Patients were randomized 3:2 to receive ixazomib (n = 395) or placebo (n = 261) on days 1, 8, and 15 of 28-day cycles for ~ 2 years or until progressive disease/toxicity. The initial 3-mg ixazomib dose was escalated to 4 mg in cycle 5, if tolerated in cycles 1-4. Safety was a secondary endpoint assessed in all treated patients; AEs were graded using Common Terminology Criteria for AEs v4.03. The rate of grade ≥ 3 AEs was higher in the ixazomib arm (19%) than in the placebo arm (5%), but the rate of discontinuation due to AEs was similar (7% vs. 5%). For AEs of clinical interest, rates were higher with ixazomib versus placebo: nausea 39% versus 15%, vomiting 27% versus 11%, diarrhea 35% versus 24%, thrombocytopenia 13% versus 3%, and peripheral neuropathy 19% versus 15%. However, the majority of events were low-grade, manageable with supportive therapy or dose reduction, and reversible, and did not result in discontinuation. There was no evidence of cumulative, long-term, or late-onset toxicity with ixazomib maintenance. Ixazomib is an efficacious and tolerable option for post-ASCT maintenance. AEs associated with ixazomib maintenance can be managed in the context of routine post-ASCT supportive care due to the limited additional toxicity. ClinicalTrials.gov NCT02181413.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo , Transplante de Células-Tronco , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autoenxertos , Compostos de Boro/administração & dosagem , Compostos de Boro/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Glicina/administração & dosagem , Glicina/efeitos adversos , Glicina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Silicatos/administração & dosagem , Silicatos/efeitos adversos , Taxa de SobrevidaRESUMO
BACKGROUND: With the advent of novel drugs improved overall survival in patients with multiple myeloma, including patients who received up-front autologous stem cell transplantation (ASCT), has been reported from several centers. Here we report on overall survival in a population-based cohort of patients receiving ASCT as first line treatment and in whom novel agents were an option for second and later lines of treatment. METHODS: Patients with multiple myeloma ≤ 65 years of age who were considered for ASCT from 01.01.2001-31.06.2005 (period 1) and from 01.07.2005 until 31.12.2009 (period 2) at Oslo University Hospital (OUH) were identified. Relevant data were collected from the patients' medical records. RESULTS: Altogether, 293/355 patients received ASCT. In all, median OS was 82.9 months in patients ≤ 60 years of age and 59.0 months in patients 61-65 years. For patients ≤ 60 years of age median OS increased from 70.6 months to 87.7 months (p = 0. 22) and median survival after start of second line therapy increased from 34.5 months to 46.5 months (p = 0.015) between the two periods. For patients 61-65 years of age median OS increased from 57.3 months to 61.2 months (p = 0. 87) and median survival after start of second line therapy was practically unchanged (32.6 months vs. 33.1 months (p = 0.97) between the periods. In patients ≤ 60 years of age salvage ASCT was used in 34% of the patients while in patients 61-65 years of age salvage ASCT was used in 7.3% of the patients. The use of salvage ASCT and novel drugs, as well as the number of treatment lines, were higher in patients ≤ 60 years of age and increased during the study period. CONCLUSION: In patients ≤ 60 years of age an increased median OS of 17 months between the two periods were noted, but the difference failed to reach statistical significance. However, a statistically significant difference in median survival of 12 months after start of second line therapy was found in this age group, which may be explained by a more active second line treatment. In patients 61-65 years only a slight increase of survival, not statistically significant, was noted between the periods.
Assuntos
Autoenxertos , Mieloma Múltiplo , Transplante de Células-Tronco , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Noruega/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Mieloma Múltiplo/patologia , Placebos , Prednisona/administração & dosagem , Indução de Remissão , Taxa de Sobrevida , Talidomida/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. METHODS: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. RESULTS: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. CONCLUSIONS: Thalidomide (50-100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Bortezomib , Estudos Cross-Over , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Pirazinas/administração & dosagem , Qualidade de Vida , Recidiva , Talidomida/administração & dosagemRESUMO
OBJECTIVE: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L. METHODS: Thirty-six elderly patients with low- and intermediate-1 risk MDS received darbepoetin (DA) 300 µg/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. RESULTS: Twenty-seven patients completed the study. Response rate to DA ± G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb >120 g/L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. CONCLUSIONS: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
Assuntos
Hemoglobinas/análise , Imageamento por Ressonância Magnética/métodos , Síndromes Mielodisplásicas/terapia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Darbepoetina alfa , Transfusão de Eritrócitos , Eritropoetina/administração & dosagem , Eritropoetina/análogos & derivados , Feminino , Ferritinas/sangue , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Masculino , Síndromes Mielodisplásicas/tratamento farmacológico , Proteínas Recombinantes , Resultado do TratamentoRESUMO
PURPOSE: To address the role of consolidation treatment for newly diagnosed, transplant eligible patients with multiple myeloma in a controlled clinical trial. PATIENTS AND METHODS: The EMN02/HOVON95 trial compared consolidation treatment with two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) or no consolidation after induction and intensification therapy, followed by continuous lenalidomide maintenance. Primary study end point was progression-free survival (PFS). RESULTS: Eight hundred seventy-eight eligible patients were randomly assigned to receive VRD consolidation (451 patients) or no consolidation (427 patients). At a median follow-up of 74.8 months, median PFS with adjustment for pretreatment was prolonged in patients randomly assigned to VRD consolidation (59.3 v 42.9 months, hazard ratio [HR] = 0.81; 95% CI, 0.68 to 0.96; P = .016). The PFS benefit was observed across most predefined subgroups, including revised International Staging System (ISS) stage, cytogenetics, and prior treatment. Revised ISS3 stage (HR, 2.00; 95% CI, 1.41 to 2.86) and ampl1q (HR, 1.67; 95% CI, 1.37 to 2.04) were significant adverse prognostic factors. The median duration of maintenance was 33 months (interquartile range 13-86 months). Response ≥ complete response (CR) after consolidation versus no consolidation before start of maintenance was 34% versus 18%, respectively (P < .001). Response ≥ CR on protocol including maintenance was 59% with consolidation and 46% without (P < .001). Minimal residual disease analysis by flow cytometry in a subgroup of 226 patients with CR or stringent complete response or very good partial response before start of maintenance demonstrated a 74% minimal residual disease-negativity rate in VRD-treated patients. Toxicity from VRD was acceptable and manageable. CONCLUSION: Consolidation treatment with VRD followed by lenalidomide maintenance improves PFS and depth of response in newly diagnosed patients with multiple myeloma as compared to maintenance alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Lenalidomida/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Quimioterapia de Consolidação , Dexametasona/efeitos adversos , Europa (Continente) , Humanos , Lenalidomida/efeitos adversos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Neoplasia Residual , Intervalo Livre de Progressão , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: Patients with multiple myeloma (MM) often have pronounced symptoms and substantially reduced quality of life. The aims of treatment are to control disease, maximise quality of life and prolong survival. Hence, health-related quality of life (HRQOL) should be an important end-point in randomised controlled trials (RCTs) in addition to traditional endpoints. We wanted to evaluate whether trials reporting HRQOL outcomes have influenced clinical decision making and whether HRQOL was assessed robustly according to predefined criteria. METHODS: A systematic review identified RCTs in MM with HRQOL assessment as a study end-point. The methodological quality of these studies was assessed according to a checklist developed for evaluating HRQOL outcomes in clinical trials. The impact of the HRQOL results on clinical decision making was assessed, using published clinical guidelines as a reference. RESULTS: Fifteen publications presenting RCTs with HRQOL as a study end-point were identified. In 13 trials, the author stated that HRQOL results should influence clinical decision making. We found, however, that the HRQOL data only had a limited impact on published treatment guidelines for bisphosphonates, high-dose treatment, interferon, erythropoiesis-stimulating agents and novel agents. CONCLUSION: The present review indicates that the there are still few RCTs in MM including HRQOL as a study end-point. Systematic incorporation of HRQOL measures into clinical trials allows for a comparison of treatment arms that includes the patients' perspective. Before the full impact on clinical decisions can be realised, the quality and methodology of collecting HRQOL data must be further improved and the results rendered more comprehensible to clinicians.
Assuntos
Mieloma Múltiplo/diagnóstico , Qualidade de Vida , Protocolos Clínicos , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
BACKGROUND: Serum free light chain (SFLC) measurements have recently come into use as an aid for diagnosing monoclonal gammopathy. We evaluated SFLC measurements in combination with serum protein electrophoresis (SPE) and clinical information for diagnosing multiple myeloma (MM) in a hospital population. METHODS: We measured SFLCs in 3818 sera received for SPE over a 1-year period when patient symptoms or biochemical findings suggested myeloma-related tissue damage (n = 1067). We reviewed SPE and SFLC results from 489 patients together with their final diagnoses obtained from the hospital information technology department. RESULTS: SFLC measurement, combined with SPE and clinical information, allowed identification of 95% of patients (38 of 40) with previously undiagnosed MM, macroglobulinemia, or primary amyloidosis. Additionally, we identified 45 patients with monoclonal gammopathy of undetermined significance (MGUS) and 4 with plasmacytoma. Of patients followed at our hospital in whom SFLCs were not measured, only 1 patient was diagnosed with MM. This patient had anemia and was mistakenly not tested for SFLCs. An abnormal kappa/lambda ratio was found in 26 of 29 patients with MM but also in 36 of 203 patients with renal impairment, polyclonal immunoresponse, or other nonhematological diagnoses. None of the 203 patients with nonhematological disease had a kappa/lambda ratio <0.05 or >10. CONCLUSIONS: The combined use of SPE, SFLC measurements, and clinical criteria allows MM to be efficiently diagnosed or excluded based on serum measurements only.
Assuntos
Eletroforese/métodos , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/diagnóstico , Humanos , Cadeias Leves de Imunoglobulina/isolamento & purificação , Pacientes Internados , Mieloma Múltiplo/sangueAssuntos
Imunoglobulinas/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Algoritmos , Biomarcadores/sangue , Transformação Celular Neoplásica , Diagnóstico Diferencial , Progressão da Doença , Humanos , Assistência de Longa Duração/métodos , Transtornos Linfoproliferativos/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Mieloma Múltiplo/diagnóstico , Prognóstico , Macroglobulinemia de Waldenstrom/diagnósticoRESUMO
BACKGROUND & AIMS: Multiple myeloma (MM) ranks among the most frequent blood cancers in adults. Optimal treatment consists of high-dose chemotherapy and autologous stem cell transplantation. Health-related quality of life (HRQoL) is reduced before, during, and after therapy. Several HRQoL items are associated with nutritional health, e.g., nausea/vomiting, appetite loss and fatigue. It is unknown whether nutritional status in MM is affected by treatment. Hence we assessed nutritional status before, during and (1/2) year after treatment-start. METHODS: We applied anthropometry (height, weight, hand-grip strength, triceps skinfold) and plasma concentrations of biomarkers to assess nutritional status. HRQoL was determined with the EORTC QLQ-C30 questionnaire. RESULTS: The anthropometrical parameters all decreased (p<0.05) during treatment, but were restored at the end of the observation period. Albumin and the fat-soluble vitamins D and E followed a similar pattern, whereas transferrin and vitamin A were unchanged (p>0.05). Interestingly, markers of thyroid function declined and remained low (p<0.05) even 6 months after start of therapy. Nutrition-associated symptoms used as markers of HRQoL worsened during therapy, but returned to pre-therapy levels. CONCLUSION: Intensive therapy in MM is associated with a decline in both nutritional status and health-related quality of life.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Estado Nutricional/efeitos dos fármacos , Transplante de Células-Tronco , Adulto , Antropometria , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Tamanho Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/fisiopatologia , Qualidade de Vida/psicologia , Transplante de Células-Tronco/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo , Transplante AutólogoRESUMO
Intensive chemotherapy is mandatory in curative treatment of acute myeloid leukemia (AML), but whether the nutritional status deteriorates during treatment, is unknown. We therefore prospectively examined anthropometric and biochemical nutritional markers during intensive chemotherapy in 26 Russian and 19 Norwegian AML patients during 9 months from diagnosis. Although the body mass index remained unchanged in both cohorts, hand grip strength and triceps skinfold thickness declined (P<0.05) during treatment before normalisation at study end. We detected a similar significant, temporary decrease in albumin, transferrin, testosterone and gonadotrophins in both cohorts. Although the fat-soluble vitamins D and E also displayed such a pattern, vitamin A dropped and remained low throughout the study in both cohorts. The Russian patients reported lower global quality of life, more symptoms and more financial concern than the Norwegians. Our data suggest a catabolic metabolism during intensive chemotherapy for AML, leading to impaired nutritional status, hypofunction of the pituitary-gonadal axis and decreased health-related quality of life.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Estado Nutricional/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antropometria , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/análise , Feminino , Gônadas/fisiopatologia , Força da Mão , Humanos , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Noruega , Hipófise/fisiopatologia , Qualidade de Vida , Federação RussaRESUMO
Earlier studies showing a negative impact of anaemia on quality of life (QOL) lack adequate adjustment for confounding factors such as disease stage and tumour response. We examined the impact of haemoglobin concentration on QOL scores of 745 multiple myeloma patients followed from diagnosis, adjusting for objective disease parameters. Data from two Nordic studies with the EORTC QLQ-C30 questionnaire were analysed using linear regression analysis. Haemoglobin was independently related only to fatigue at baseline (P = 0.001) and at 12 months (P = 0.010). In multivariate analysis, extent of skeletal disease was at least as strong a predictor for fatigue at diagnosis as haemoglobin and was also related to other important QOL scores such as physical functioning, role functioning, global QOL and pain (P < 0.001). At 12 months' follow-up, response to therapy was related to physical functioning (P < 0.001) and pain (P = 0.001). In conclusion, haemoglobin and extent of skeletal disease were both predictors for fatigue in patients with newly diagnosed multiple myeloma, but extent of skeletal disease was also associated with other important QOL scores. During follow-up, response to therapy emerged as an important predictor variable. When examining the effect of haemoglobin on QOL, it is essential to adjust for disease parameters and response to therapy in order not to overestimate the impact of haemoglobin on QOL. Our findings imply that uncontrolled studies on the effect of erythropoietin (EPO) in cancer patients may be making exaggerated claims for the effect of EPO on QOL.
Assuntos
Hemoglobinas/análise , Mieloma Múltiplo/sangue , Mieloma Múltiplo/fisiopatologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia , Doenças Ósseas/patologia , Doenças Ósseas/fisiopatologia , Eritropoetina/farmacologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Neoplasias , Noruega , Resistência Física , Análise de Regressão , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: Without clear guidelines, clinicians and health care providers are often uncertain how to interpret (quality of life) QOL scores. To facilitate the interpretation, QOL scores of multiple myeloma patients at diagnosis were compared with the scores of a reference population, and the clinical significance of QOL score differences and of changes in scores over time was assessed. METHODS: Data from two prospective Nordic Myeloma Study Group trials (221 patients <60 yr treated with high dose chemotherapy, and 203 patients >60 yr treated with melphalan and prednisone) were analysed. The EORTC QLQ-C30 questionnaire was used. The results were compared with the scores of an age- and gender-adjusted Norwegian reference population (n = 3000), using a regressional approach. The magnitude of the observed differences and of score changes during follow-up was estimated as effect size [score difference (SD)] and according to a subjective rating system as small, moderate or large. RESULTS: At diagnosis, the most distressing problems were pain and fatigue, reduced physical functioning, limitations in role functioning and reduced overall QOL. These differences from the reference population were statistically significant (P < 0.001), and large or moderate according to the rating systems. After the start of treatment, small to moderate improvement in mean QOL scores were observed for most domains. CONCLUSION: Comparison with a reference population eases the interpretation of QOL scores and prevents overestimation of symptoms and underestimation of subjective treatment response. The agreement between the two methods to evaluate the meaning of differences and changes in QOL scores was good.
Assuntos
Mieloma Múltiplo/psicologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Feminino , Humanos , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Mieloma Múltiplo/tratamento farmacológico , Prednisona/uso terapêutico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Valores de Referência , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0.200/h, 0.140/h, 0.886 l/kg, 0.126 l/h/kg and 4.98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.
Assuntos
Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Idoso , Proteínas Sanguíneas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hemoglobinas/metabolismo , Humanos , Imunoglobulinas/metabolismo , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Análise de Sobrevida , Talidomida/efeitos adversos , Talidomida/farmacocinética , Resultado do TratamentoRESUMO
We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo = 500 U/l and a transfusion need of < 2 units/month predicted a high probability of response to treatment, S-Epo > 500 U/l and >/= 2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.