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Human cancer arises from a population of cells that have acquired a wide range of genetic alterations, most of which are targets of therapeutic treatments or are used as prognostic factors for patient's risk stratification. Among these, copy number alterations (CNAs) are quite frequent. Currently, several molecular biology technologies, such as microarrays, NGS and single-cell approaches are used to define the genomic profile of tumor samples. Output data need to be analyzed with bioinformatic approaches and particularly by employing computational algorithms. Molecular biology tools estimate the baseline region by comparing either the mean probe signals, or the number of reads to the reference genome. However, when tumors display complex karyotypes, this type of approach could fail the baseline region estimation and consequently cause errors in the CNAs call. To overcome this issue, we designed an R-package, BoBafit , able to check and, eventually, to adjust the baseline region, according to both the tumor-specific alterations' context and the sample-specific clustered genomic lesions. Several databases have been chosen to set up and validate the designed package, thus demonstrating the potential of BoBafit to adjust copy number (CN) data from different tumors and analysis techniques. Relevantly, the analysis highlighted that up to 25% of samples need a baseline region adjustment and a redefinition of CNAs calls, thus causing a change in the prognostic risk classification of the patients. We support the implementation of BoBafit within CN analysis bioinformatics pipelines to ensure a correct patient's stratification in risk categories, regardless of the tumor type.
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Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37-8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18-10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.
Assuntos
Mieloma Múltiplo/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Idoso , Deleção Cromossômica , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , PrognósticoRESUMO
The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.
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Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that presents as a single mass of monoclonal plasma cells, located either extramedullary or intraosseous. In some patients, a bone marrow aspiration can detect a low monoclonal plasma cell infiltration which indicates a high risk of early progression to an overt myeloma disease. Before treatment initiation, whole body positron emission tomography-computed tomography or magnetic resonance imaging should be performed to exclude the presence of additional malignant lesions. For decades, treatment has been based on high-dose radiation, but studies exploring the potential benefit of systemic therapies for high-risk patients are urgently needed. In this review, a panel of expert European hematologists updates the recommendations on the diagnosis and management of patients with solitary plasmacytoma.
Assuntos
Plasmocitoma/diagnóstico , Plasmocitoma/terapia , Gerenciamento Clínico , Europa (Continente)/epidemiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Plasmocitoma/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Resultado do TratamentoRESUMO
Precise assessment of response to therapy is of high importance in every phase of multiple myeloma (MM). In addition to the well-established role of monoclonal protein for clinical monitoring, several methods of minimal residual disease evaluation, both inside and outside the bone marrow (BM), are to date available. Next generation flow cytometry and sequencing are probably the best approaches at the BM level, being highly sensitive and uniformly applied. FDG PET/CT is the best imaging technique for evaluating and monitoring response to therapy outside the BM. Functional whole-body MRI techniques (DCE and DWI) seem promising for response evaluation and need further studies. Standardization of most of these techniques is in progress.
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Mieloma Múltiplo/diagnóstico , Biomarcadores , Medula Óssea/metabolismo , Medula Óssea/patologia , Citometria de Fluxo , Humanos , Imagem Multimodal , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/terapia , Proteínas do Mieloma/metabolismo , Neoplasia Residual/diagnóstico , Avaliação de Resultados em Cuidados de Saúde , Resultado do TratamentoRESUMO
Despite significant improvement in outcomes have been observed for multiple myeloma (MM) patients over the past 10-15 years, mainly due to the introduction of novel agents targeting the tumor clone and the bone marrow microenvironment, treatment of refractory and/or relapsed (RR) disease remains a challenge, particularly for patients who have failed prior bortezomib- and lenalidomide-based therapies. More recently, new drugs with different mechanisms of action, including second generation proteasome inhibitors, third generation immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies, have been developed and are under investigation, further increasing treatment options for RRMM patients. Overall, novel agent-based triplet combinations demonstrated superior response rates and prolonged disease control when compared with two-drug regimens in several randomized clinical trials, without adding any relevant additional toxicity. Salvage triplet therapies are likely to play a key role in overcoming drug-resistance and hold promise to further improve long-term outcomes of RRMM patients.
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Antineoplásicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Lenalidomida , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Inibidores de Proteassoma/uso terapêutico , Terapia de Salvação , Talidomida/análogos & derivados , Talidomida/uso terapêuticoRESUMO
Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment. Results demonstrated that an Hh-gene signature was able to cluster patients in two subgroups characterized by the opposite Hh pathway expression in mature plasma cells and their precursors. Strikingly, patients characterized by Hh hyperactivation in plasma cells, but not in their B cells, displayed high genomic instability and an unfavorable outcome in terms of shorter progression-free survival (hazard ratio: 1.92; 95% confidence interval: 1.19-3.07) and overall survival (hazard ratio: 2.61; 95% confidence interval: 1.26-5.38). These results suggest that the mechanisms triggered by the Hh pathway ultimately led to identify a more indolent vs a more aggressive biological and clinical subtype of MM. Therefore, patient stratification according to their molecular background might help the fine-tuning of future clinical and therapeutic studies.
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Linfócitos B/patologia , Proteínas Hedgehog/metabolismo , Mieloma Múltiplo/diagnóstico , Plasmócitos/patologia , Animais , Antígenos CD19 , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Camundongos SCID , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/metabolismo , Plasmócitos/imunologia , Plasmócitos/metabolismo , Prognóstico , Transdução de Sinais , Sindecana-1 , Células Tumorais CultivadasRESUMO
Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide (18)F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58-5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM.
Assuntos
Mieloma Múltiplo/diagnóstico por imagem , Osteólise/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Idoso , Progressão da Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios XRESUMO
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.
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Mieloma Múltiplo , Guias de Prática Clínica como Assunto , Antineoplásicos/uso terapêutico , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Recidiva , Terapia de Salvação/métodosRESUMO
PURPOSE: To assess the clinical relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM), 50 patients were monitored while they were in complete clinical remission (CCR) after autologous or allogeneic stem-cell transplantation. PATIENTS AND METHODS: Stringent molecular monitoring using clonal markers based on rearranged immunoglobulin heavy-chain genes was performed in 44 of 50 MM patients in CCR. Molecular clinical remission (MCR) was defined as more than one consecutive negative polymerase chain reaction (PCR) test result. RESULTS: Twelve (27%) of 44 molecularly monitored patients achieved MCR; four of the 12 became PCR-positive, and one of these four relapsed. In comparison with patients who did not achieve MCR, patients who achieved MCR had a significantly lower relapse rate (41% v 16%; P <.05) and longer relapse-free survival (35 v 110 months; P <.005). Fourteen of 26 patients in CCR who had received allografts were evaluated on a molecular basis: seven (50%) of the 14 achieved MCR and did not relapse; one of the seven remaining patients relapsed. Thirty of 47 patients in CCR who received autografts were evaluated on a molecular basis: five (16%) of the 30 achieved MCR; two of these five became PCR-negative, and one of these two relapsed. Ten of the 25 remaining patients later relapsed. For these nonrandomized groups, the higher MCR rate after allograft procedures was statistically significant (P <.01; Fisher's exact test). CONCLUSION: MCR can be obtained in a relatively high proportion of MM patients who have achieved CCR after undergoing allograft procedures and in a smaller fraction of patients after undergoing autograft procedures. In approximately one fourth of MM patients who achieve CCR after transplantation, it may be possible to keep the disease burden constantly below the PCR threshold. Because MCR was associated with prolonged relapse-free survival, these patients could have a relatively favorable clinical outcome.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Biomarcadores Tumorais/análise , DNA de Neoplasias/análise , Feminino , Rearranjo Gênico , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Neoplasia Residual , Reação em Cadeia da Polimerase , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Transplante HomólogoRESUMO
Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15 microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/microI and 20000 platelets/microI were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.
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Transplante de Células-Tronco Hematopoéticas , Falência Renal Crônica/etiologia , Mieloma Múltiplo/terapia , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/administração & dosagem , Colangiocarcinoma , Terapia Combinada , Creatinina/sangue , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Hiperbilirrubinemia/etiologia , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Falência Renal Crônica/terapia , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Segunda Neoplasia Primária , Indução de Remissão , Diálise Renal , Segurança , Estomatite/etiologia , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34(+) cell yields as compared with TD (9.75 vs 10.76 × 10(6) CD34(+) cells/kg, P=0.220). For poor mobilizers (<4 × 10(6) CD34(+) cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P<0.0001; PFS: 16 vs 46%, P<0.0001; OS: 50 vs 80%, P<0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34(+) cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.
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Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Talidomida/administração & dosagem , Autoenxertos , Feminino , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
The present clinical trial was undertaken to investigate the toxicity and antimyeloma activity of busulfan (BU) and cyclophosphamide (CY) at the maximum tolerated doses of, respectively, 16 mg/kg and 200 mg/kg (BU-CY 4) as conditioning therapy for allogeneic bone marrow transplantation (BMT) in 19 consecutive patients with multiple myeloma (MM). Twelve (63%) had failed to respond to prior chemotherapy, while the remaining 37% had chemosensitive disease. No life-threatening or fatal regimen-related complications were observed. The incidence of veno-occlusive disease of the liver was zero according to Jones' criteria and 21% according to McDonald's system. Transplant-related mortality was 37%. Using stringent criteria, the frequency of complete remission (CR) was 42% among all patients and 53% among those who could be evaluated. With a median follow-up of 21 months for all patients and 66 months for survivors, the actuarial probability of survival and event-free survival at 4 years from BMT was 26% (95% CI: 7-46) and 21% (95% CI: 3-39), respectively. A more favorable outcome of transplantation was observed in the subgroup of patients with chemosensitive disease who had a transplant-related mortality of 14%, an overall CR rate of 86% (95% CI: 49-97) and a 4-year projected probability of event-free survival of 57% (95% CI: 20-93). Four of these patients are currently alive in continuous CR after 54, 66, 80 and 94 months, respectively. It is concluded that BU-CY 4 as conditioning for allogeneic transplantation for MM is associated with acceptable morbidity and relatively low mortality. This regimen exerts substantial antimyeloma activity, resulting in a high CR rate and durable responses, especially in patients with chemosensitive disease. Long-lasting remission and probable cure is possible following allogeneic stem cell transplantation for MM.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Bussulfano/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Recidiva , Transplante HomólogoRESUMO
The use of an Integrated Environmental Monitoring System is an innovative and very important approach for the determination of environmental impacts due to a contamination source. In the present work, the methodological approach is described and applied to the case study of a MSW incineration plant. Heavy metals were chosen as Environmental Indicators. Gaseous emissions were measured and correlated to wet and dry depositions, soil and vegetation samples. Results show a good correlation between stack emissions and atmospheric depositions; less with soil and vegetation, but these results are important in order to design a standard procedure for an Integrated Monitoring System.
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Monitoramento Ambiental/métodos , Poluentes Ambientais/análise , Incineração , Metais Pesados/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/normas , Incineração/legislação & jurisprudência , Incineração/normas , Itália , Software , Poluentes do Solo/análise , Árvores/química , Verduras/químicaRESUMO
Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma.
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Mieloma Múltiplo/terapia , Humanos , Monitorização Fisiológica , Mieloma Múltiplo/fisiopatologia , Recidiva , Resultado do TratamentoRESUMO
The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM) has continued to evolve in recent years. The novel agents thalidomide, bortezomib, and lenalidomide have been successfully incorporated into induction therapy in preparation for ASCT and are currently being investigated also as post-ASCT consolidation and maintenance therapy. Consolidation treatment is generally short term and aims to increase the frequency and depth of response obtained with the previous treatment phases, including novel agent-based induction therapy and ASCT. This review will focus on recent trials of novel agents as post-ASCT consolidation therapy, offering an overview of pros and cons of this new treatment strategy in the ASCT sequence for MM patients.
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Quimioterapia de Consolidação , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/administração & dosagem , Bortezomib , Ensaios Clínicos como Assunto , Humanos , Lenalidomida , Pirazinas/administração & dosagem , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Transplante Autólogo/métodos , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of our study was to compare the accuracy of contrast enhanced MRI and FDG PET-CT in the staging, treatment evaluation and follow-up of multiple myeloma. METHODS: We retrospectively reviewed 210 PET-CT and 210 MRI studies of patients affected by multiple myeloma. MRI was always performed within 15 days of PET-CT. All the images have been evaluated by two expert oncologic radiologists. RESULTS: Patient population included 81 females and 110 males (age 61.9 ± 9.9 years-old). Sixty-two patients have been evaluated at diagnosis, 58 at the end of therapies and 90 during follow-up. In 12/62 patients (19.4%) at diagnosis, differences between MRI and PET-CT findings determined changes in the staging: PET-CT was responsible for 11 down-staging (17.7%) and MRI only for one (1.6%). In 27/40 patients (67.5%) with good or complete clinical response to therapies the normalization of findings was faster for PET-CT than MRI. Ten out of 90 patients (10/90 - 11.1%) in follow-up protocol presented clinical recurrence of the disease: MRI detected active lesions in 8 of them (80.0%) and PET-CT in 5 patients (50.0%, all detected by MRI too). CONCLUSIONS: MRI achieved better results than PET-CT in the staging and in patients with multiple myeloma recurrence. PET-CT, showed prompt change of imaging findings, faster than MRI, in patients with positive response to therapy.
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Fluordesoxiglucose F18 , Gadolínio , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Mieloma Múltiplo/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Humanos , Quimioterapia de Indução , Talidomida/administração & dosagem , Transplante AutólogoRESUMO
BACKGROUND: Thalidomide is effective as a first-line therapy for the treatment of multiple myeloma (MM), but its use is limited by peripheral neurotoxicity. OBJECTIVE: To study the occurrence of both myeloma-related neuropathy and thalidomide-induced neuropathy in 31 patients with newly diagnosed MM. METHODS: Clinical and electrophysiologic examinations were performed in 31 patients with newly diagnosed MM before and after 4 months of therapy with thalidomide (200 mg/day, total dose: 21 g) aimed at debulking MM, before autologous transplantation. After transplantation, the patients took thalidomide, 200 mg/day for another 3 months (total dose over three months: 18 g) and then underwent a final clinical and electrophysiologic checkup. RESULTS: At baseline, four patients presented a mild sensorimotor peripheral neuropathy related to MM, which tended to worsen slightly during treatment with thalidomide. At the end of treatment, 83% of the patients had clinical and electrophysiologic evidence of a mild sensory rather than motor, axonal, length-dependent polyneuropathy, whereas 100% of the patients showed improvement to the basic pathology (>or=partial response). CONCLUSIONS: Peripheral neuropathy, sometimes subclinical, and mild in our patients, is a common, early side effect of thalidomide therapy. The high doses (21 g) used in all patients for a relatively short time (4 months) rule out any correlations between neuropathy, total dose, and duration of treatment.