RESUMO
The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.
Assuntos
Neoplasias de Plasmócitos , Humanos , Estudos Prospectivos , Idoso , Feminino , Pessoa de Meia-Idade , Masculino , Japão , Neoplasias de Plasmócitos/terapia , Transplante Autólogo , Prognóstico , Taxa de Sobrevida , Adulto , Transplante de Células-Tronco Hematopoéticas , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/tratamento farmacológico , População do Leste AsiáticoRESUMO
CASE PRESENTATION: A 65-year-old man with no past medical history sought treatment at the hospital with lower extremity swelling, pain, tingling in a stocking-glove distribution, and syncope. He reported a 23-pound unintentional weight loss. He felt unsteady walking with a couple of falls, and his exercise tolerance was limited to several hundred feet. He did not report vision changes, dysphagia, bowel or bladder problems, tremor, orthopnea, lightheadedness, or chest pain. He did not report any history of substance misuse, high-risk sexual behavior, or concerning exposures. The patient was admitted for further workup.
Assuntos
Hipertensão Pulmonar/diagnóstico , Neoplasias de Plasmócitos/diagnóstico , Síndrome POEMS/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Edema/etiologia , Edema/fisiopatologia , Tolerância ao Exercício , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Lenalidomida/administração & dosagem , Masculino , Neoplasias de Plasmócitos/complicações , Neoplasias de Plasmócitos/terapia , Síndrome POEMS/complicações , Síndrome POEMS/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Transplante de Células-Tronco , Síncope/etiologia , Síncope/fisiopatologia , Tadalafila/uso terapêutico , Redução de PesoAssuntos
Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias de Plasmócitos/mortalidade , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Gerenciamento Clínico , Humanos , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/terapia , PrognósticoRESUMO
Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PAhigh, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PAhigh at higher risk of progression and death.
Assuntos
Apoptose , Biomarcadores Tumorais , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/etiologia , Lesões Pré-Cancerosas , Idoso , Biópsia , Medula Óssea/patologia , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Prognóstico , Curva ROC , Fatores de Risco , Avaliação de SintomasRESUMO
Oncolytic viruses exert an anti-tumour effect through two mechanisms: direct oncolytic and indirect immune-mediated mechanisms. Although oncolytic herpes simplex virus type 1 (HSV-1) has been approved for melanoma treatment and is being examined for its applicability to a broad spectrum of malignancies, it is not known whether it has an anti-myeloma effect. In the present study, we show that the third-generation oncolytic HSV-1, T-01, had a direct oncolytic effect on five of six human myeloma cell lines in vitro. The anti-tumour effect was enhanced in the presence of peripheral blood mononuclear cells (PBMCs) from healthy individuals and, to a lesser extent, from patients with myeloma. The enhancing effect of PBMCs was abrogated by blocking type I interferons (IFNs) or by depleting plasmacytoid dendritic cells (pDCs) or natural killer (NK) cells, suggesting that pDC-derived type I IFNs and NK cells dominated the anti-tumour effect. Furthermore, the combination of T-01 and lenalidomide exhibited enhanced cytotoxicity, and the triple combination of T-01, lenalidomide and IFN-α had a maximal effect. These data indicate that oncolytic HSV-1 represents a viable therapy for plasma cell neoplasms through direct oncolysis and immune activation governed by pDCs and NK cells. Lenalidomide is likely to augment the anti-myeloma effect of HSV-1.
Assuntos
Herpesvirus Humano 1/imunologia , Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Neoplasias de Plasmócitos/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/imunologia , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Interferon-alfa/uso terapêutico , Masculino , Camundongos SCID , Neoplasias de Plasmócitos/imunologia , Neoplasias de Plasmócitos/patologiaRESUMO
BACKGROUND: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. METHODS: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31â993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. FINDINGS: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival. INTERPRETATION: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. FUNDING: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.
Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Neoplasias Hematológicas/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Feminino , Seguimentos , Neoplasias Hematológicas/terapia , Humanos , Pacientes Internados , Itália/epidemiologia , Leucemia/epidemiologia , Leucemia/terapia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/terapia , Neoplasias de Plasmócitos/epidemiologia , Neoplasias de Plasmócitos/terapia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND AND OBJECTIVES: Allogenic hematopoietic stem cell transplantation (allo-SCT) is a curative therapy for hematological malignancies, but transplant-related mortality (TRM) remains a concern. This study aimed to determine the efficacy of capsule endoscopy (CE) by evaluating the correlation between inflammatory findings on CE and TRM. METHODS: The data of patients after allo-SCT were retrospectively collected. The association between findings on CE and TRM at 100 days from the CE was evaluated. RESULTS: Of the 94 patients included in the study, 47 showed inflammatory findings on CE. The findings were diagnosed as graft-versus-host disease (GVHD; n = 17), cytomegalovirus (CMV) infection (n = 14), and GVHD with CMV infection (n = 16). Of the 47 patients, 13 (28%) had TRM. Endoscopic diagnoses of these TRM cases were GVHD (n = 4), CMV infection (n = 0), and GVHD with CMV infection (n = 9). In contrast, in the remaining 47 patients who showed no inflammatory findings on CE, 2 patients (4%) had TRM. The proportion of TRM was higher in patients with inflammatory findings than in those without it (28 vs. 4%, p < 0.01). CONCLUSIONS: CE may predict TRM in patients who developed gastrointestinal symptoms after allo-SCT.
Assuntos
Endoscopia por Cápsula/estatística & dados numéricos , Infecções por Citomegalovirus/mortalidade , Gastroenteropatias/mortalidade , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Adolescente , Adulto , Idoso , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia/terapia , Linfoma/terapia , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Monoclonal plasma cell proliferative disorders comprise a wide spectrum of diseases associated to clonal B-cell expansion. Serum protein electrophoretic profile (SPEP) and circulating free light chains (FLCs) levels are the mainstay of diseases management. Recently, soluble (s) Syndecan-1 (SDC1, CD138) produced by myeloma plasma cells has been suggested in the monitoring and follow-up of patients with myeloma. The aim of our study is to evaluate sCD138 in addition with FLCs and SPEP for the screening of patients with different evolutive disease pathways. PATIENTS AND METHODS: Sera from 73 patients with monoclonal gammopathy of undetermined significance (MGUS), 120 smoldering and 42 multiple myeloma (SMM and MM, respectively), 70 HCV-related mixed cryoglobulinemia (MC), 35 B-cell non-Hodgkin's lymphoma (B-NHL) and sera from 50 healthy donors (HD), were tested for sCD138, FLCs (assessed by means of ELISA and turbidimetric assay, respectively) and electrophoresis pattern (performed on Capillarys system) for the generation of a novel biomarker score (BS). RESULTS: Our results were grouped according to the two main lines of disease progression (vs. MM or B-NHL): in one group we found BS mean values of 0.2, 3.4, 5.3, 7.1 for HD, MGUS, SMM and MM, respectively; in the other group of 0.2, 4.4, 6.7 for HD, MC and B-NHL. CONCLUSIONS: We showed that BS mean values follow the ingravescence disease status towards the two main lines of progression to cancerous conditions; it could represent an additional useful tool in the management of screening and/or follow-up.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/terapia , Sindecana-1/sangue , Adulto , Eletroforese das Proteínas Sanguíneas , Progressão da Doença , Feminino , Humanos , Masculino , Programas de Rastreamento , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo/sangue , Neoplasias de Plasmócitos/sangue , Nefelometria e Turbidimetria/métodos , Paraproteinemias/sangue , Valor Preditivo dos Testes , PrognósticoAssuntos
Esôfago/diagnóstico por imagem , Hamartoma/diagnóstico por imagem , Hamartoma/patologia , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Idoso , Diagnóstico Diferencial , Embolização Terapêutica , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Esôfago/patologia , Hamartoma/complicações , Humanos , Pneumopatias/complicações , Masculino , Neoplasias de Plasmócitos/complicações , Neoplasias de Plasmócitos/patologia , Neoplasias de Plasmócitos/terapia , Recidiva , Tomografia Computadorizada por Raios XRESUMO
Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has been demonstrated in angiogenesis associated with hematological tumors. In this review we focused on the role of mast cells in angiogenesis in human plasma cell malignancies. In this context, mast cells might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, permitting the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression.
Assuntos
Mastócitos/imunologia , Mastócitos/metabolismo , Neoplasias de Plasmócitos/etiologia , Neoplasias de Plasmócitos/metabolismo , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Animais , Biomarcadores , Medula Óssea/metabolismo , Medula Óssea/patologia , Contagem de Células , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/metabolismo , Suscetibilidade a Doenças , Humanos , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Neoplasias de Plasmócitos/patologia , Neoplasias de Plasmócitos/terapia , Plasmocitoma/etiologia , Plasmocitoma/metabolismo , Plasmocitoma/patologia , Microambiente TumoralRESUMO
TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is a newly described clinical entity that is generally considered a plasma cell dyscrasia with multiple system involvement. The etiology and pathophysiology of this condition remains elusive. Nevertheless, clonal plasma cells and monoclonal protein appear to be major contributors. The early diagnosis of TEMPI syndrome is essential because therapies targeting the underlying plasma cells can lead to a dramatic response. Bortezomib-based chemotherapy, daratumumab monotherapy, and autologous hematopoietic stem cell transplantation can result in reversal of most manifestations. Nevertheless, the diagnosis of TEMPI syndrome remains a substantial challenge owing to its rarity and the complexity of clinical presentations. TEMPI syndrome is often misdiagnosed as other causes of erythrocytosis, resulting in a delayed diagnosis and further clinical deterioration. The aim of the present review was to present the clinical and biologic features of TEMPI syndrome, highlighting the differential diagnosis and outlining the present understanding of its pathophysiology and treatment.
Assuntos
Neoplasias de Plasmócitos/patologia , Paraproteinemias/patologia , Policitemia/patologia , Telangiectasia/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Neoplasias de Plasmócitos/complicações , Neoplasias de Plasmócitos/terapia , Paraproteinemias/complicações , Paraproteinemias/terapia , Policitemia/complicações , Policitemia/terapia , Prognóstico , Síndrome , Telangiectasia/complicações , Telangiectasia/terapia , Transplante AutólogoRESUMO
The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease. The management of light chain amyloidosis depends on the presence and severity of heart disfunction. If present, intensification with an autologous stem cell transplantation (ASCT) is not recommended. Further aggregation of misfolded light chains could be prevented by doxycycline or monoclonal antibodies targeting amyloid deposits. Initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens. For relapsing patients, one can consider proteasome inhibitors, immunomodulatory agents, melphalan or daratumumab. Because intact or light-chain immunoglobulins are also the culprits for MIDD, the small monoclonal plasma cells' clones should be treated and generally respond well to bortezomib-based treatment. POEMS syndrome is a well-defined clinical entity that can present as solitary bone lesions or disseminated disease. Radiation therapy is used for patients with localized disease and result in long-lasting response. Systemic treatment should be proposed to patients with disseminated disease, but regimens that can worsen a pre-existing polyneuropathy should be avoided. PPCL is located at the other end of the spectrum of plasma cell disorders and is associated with an aggressive disease course and poor prognosis. It requires an imminent, multi-phase and novel agents-based therapy, including induction, ASCT, consolidation and maintenance, with short treatment-free intervals. Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic stem cell transplantation can be used in selected patients.
Assuntos
Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Gerenciamento Clínico , Europa (Continente) , Humanos , Leucemia Plasmocitária/diagnóstico , Leucemia Plasmocitária/terapia , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/terapia , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: -The values of SEER site recode variables are based on the primary site and histology data fields submitted to SEER by the registries. The site recode variables define the major cancer site/histology groups that are commonly used in the reporting of cancer incidence data and are added to the SEER databases as a convenience for researchers. These codes and definitions are periodically updated and changed by the National Cancer Institute as newer and more applicable information becomes available. Because this myeloma analysis includes cases diagnosed 2010+, the ICD-O-3 recode-updates with adjustment for WHO 2008 hematopoietic histologies that account for changes in the obsolete classification of hematopoietic histology codes, and the assignment of new names (ie, multiple myeloma-MM - to - plasma cell myeloma-PCM) is adhered to and used here. Plasma cell myeloma (PCM) is a bone-marrow based multifocal plasma cell malignancy (primary site C421). PCM is characterized by a single clone of plasma cells, believed to be derived from lymphoid B cells, and spans a clinical spectrum from asymptomatic to aggressive forms, plus disorders caused by the deposition of abnormal immunoglobulin chains in tissue. The current myeloma group ICD-O-3 histologic morphology types consists of: ICD-O-3 9731: Plasmacytoma, NOS, occurring in bone (osseous plasmacytoma malignancy data reportable to SEER only beginning since 1986); ICD-O-3 9732: Plasma cell myeloma - composed of three clinical variants: a) asymptomatic, b) Non-secretory myeloma, and c) Plasma cell leukemia (all coded to 9732); ICD-O-3 9734: Extramedullary plasmacytoma; anatomic sites other than bone. OBJECTIVE: -Using the statistical database of SEER*Stat 8.3.4 (produced 4/14/2017 for diagnosis years 1973-2014), to assess, determine, compare, and summarize the occurrence, long-term survival and mortality indices of the three morphologic types of myeloma by age, sex, race and stage in two-cohort entry time-periods (1973-1994 and 1995-2014). All analyses are accomplished within the context of current SEER Site Recode ICD-O-3 (1/27/2003) definitions, terminologies and descriptions, and also in accordance with the rules of the consolidated Hematopoietic and Lymphoid Neoplasm Coding Manual data base (effective 1/1/2010 - release date January 2015). METHODS: -Population data including 111,041 cases collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Frequency Database (18 SEER Registries Research Data + Hurricane Katrina Impacted Louisiana Cases, November 2016 Submission, 1973-2014 varying) for diagnosis years 1973-2014: Relative Survival Statistics were analyzed in two cohorts: 1973-1994 and 1995-2014. Survival statistics were derived from: SEER*Stat Database: Incidence - SEER 9 Regs Research Data, November 2016 Submission (1973-2014)
Assuntos
Neoplasias Ósseas , Neoplasias de Plasmócitos , Plasmocitoma , Programa de SEER , Adolescente , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Fenótipo , Plasmocitoma/mortalidade , Plasmocitoma/terapia , Sistema de Registros , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The European Society for Blood and Marrow Transplantation Chronic Malignancies Working Party held a preceptorship meeting in Turin, Italy on 25-26 September 2014, to discuss the role of stem cell transplantation (SCT) in the treatment of multiple myeloma and other plasma cell disorders. Scientists and clinicians working in the field gathered to discuss a variety of topics including the results of recent clinical trials, basic research, the concept of minimal residual disease, and immune modulation. As individual presentations revealed, important advances have occurred in our understanding of the pathophysiology of myeloma and the role that SCT, along with other forms of immunotherapy, plays in treating it. Each presentation stimulated discussion and exchange of ideas among the attendants. We decided to summarize and, importantly, to update the meeting proceedings in this review to share stimulating discussions and ideas on potentially novel treatment strategies among clinicians.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Neoplasias de Plasmócitos/terapia , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Separação Celular , Terapia Combinada , Quimioterapia de Consolidação , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Quimioterapia de Manutenção , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Neoplasia Residual , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/mortalidade , Recidiva , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Concomitant plasma cell (PCN) and B-cell neoplasms (BCN) in a single patient have been infrequently reported. This study reviewed nine such patients at the institution - six had multiple myeloma (MM) associated with a BCN (MM/B group) and three had AL amyloidosis (ALA) with a BCN (ALA/B group). This study describes two syndromes of MM/B - three patients presented with CLL and subsequently developed MM, while three presented with MM and monoclonal B-cell lymphocytosis. In the ALA/B group, all three patients had systemic ALA and a BCN. Responses of the BCN and PCN to treatment correlated. In the two patients whose MM relapsed, the BCN simultaneously relapsed. The finding that the BCN may relapse in tandem with the MM argues against a coincidental relationship between the two.
Assuntos
Leucemia de Células B/complicações , Leucemia de Células B/diagnóstico , Linfoma de Células B/complicações , Linfoma de Células B/diagnóstico , Neoplasias de Plasmócitos/complicações , Neoplasias de Plasmócitos/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Leucemia de Células B/mortalidade , Leucemia de Células B/terapia , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Fenótipo , Resultado do TratamentoRESUMO
DISEASE OVERVIEW: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. RISK-ADAPTED THERAPY: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3-6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. The benefit of anti-VEGF antibodies is conflicting. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.
Assuntos
Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/terapia , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Humanos , Neoplasias de Plasmócitos/metabolismo , Neoplasias de Plasmócitos/patologia , Síndrome POEMS/metabolismo , Síndrome POEMS/patologia , Medição de RiscoRESUMO
Chimeric antigen receptor (CAR) T-cell therapy has recently come into the spotlight due to impressive results in patients with B-cell acute lymphoblastic leukemia. By targeting CD19, a marker expressed most B-cell tumors, as well as normal B cells, CAR T-cell therapy has been investigated as a treatment strategy for B-cell leukemia and lymphoma. This review will discuss the successes of this therapy for the treatment of B-cell acute lymphoblastic leukemia and the challenges to this therapeutic strategy. We will also discuss application of CAR T-cell therapy to chronic lymphocytic leukemia and other B-cell malignancies including a follicular lymphoma, diffuse large B-cell lymphoma, as well as acute and plasma cell malignancies.
Assuntos
Neoplasias Hematológicas/terapia , Imunoterapia Adotiva/métodos , Neoplasias de Plasmócitos/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/transplante , Animais , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Humanos , Neoplasias de Plasmócitos/imunologia , Neoplasias de Plasmócitos/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Receptores de Antígenos de Linfócitos T/genética , Proteínas Recombinantes de Fusão/genética , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/µL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated with cost savings of approximately $1406 per patient utilizing average wholesale price.