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1.
Clin Nucl Med ; 44(11): e624-e626, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31584492

RESUMO

F-Fluorothymidine-positron emission tomography with CT fusion ([F]FLT-PET/CT) offers a unique and non-invasive method for three-dimensional localization and quantification of functional bone marrow. [F]FLT-PET/CT has potential application in radiotherapy planning when risk of marrow toxicity is a significant clinical concern. In this patient with chemo-refractory, transformed lymphoma and treatment-induced cytopenias, [F]FLT-PET/CT was a novel and useful adjunct to (1) image the distribution of functional bone marrow reserve, (2) guide "marrow-sparing" radiotherapy planning, and (3) quantify the effects of radiotherapy-induced bone marrow suppression both in-field and out-of-field.

2.
Palliat Support Care ; : 1-11, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31595861

RESUMO

OBJECTIVES: Psychosocial interventions that mitigate psychosocial distress in cancer patients are important. The primary aim of this study was to examine the feasibility and acceptability of an adaptation of the Mindful Self-Compassion (MSC) program among adult cancer patients. A secondary aim was to examine pre-post-program changes in psychosocial wellbeing. METHOD: The research design was a feasibility and acceptability study, with an examination of pre- to post-intervention changes in psychosocial measures. A study information pack was posted to 173 adult cancer patients 6 months-5 years post-diagnosis, with an invitation to attend an eight-week group-based adaptation of the MSC program. RESULTS: Thirty-two (19%) consented to the program, with 30 commencing. Twenty-seven completed the program (mean age: 62.93 years, SD 14.04; 17 [63%] female), attending a mean 6.93 (SD 1.11) group sessions. There were no significant differences in medico-demographic factors between program-completers and those who did not consent. However, there was a trend toward shorter time since diagnosis in the program-completers group. Program-completers rated the program highly regarding content, relevance to the concerns of cancer patients, and the likelihood of recommending the program to other cancer patients. Sixty-three percent perceived that their mental wellbeing had improved from pre- to post-program; none perceived a deterioration in mental wellbeing. Small-to-medium effects were observed for depressive symptoms, fear of cancer recurrence, stress, loneliness, body image satisfaction, mindfulness, and self-compassion. SIGNIFICANCE OF RESULTS: The MSC program appears feasible and acceptable to adults diagnosed with non-advanced cancer. The preliminary estimates of effect sizes in this sample suggest that participation in the program was associated with improvements in psychosocial wellbeing. Collectively, these findings suggest that there may be value in conducting an adequately powered randomized controlled trial to determine the efficacy of the MSC program in enhancing the psychosocial wellbeing of cancer patients.

3.
Blood ; 134(16): 1346-1350, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31467061

RESUMO

Extracorporeal photopheresis (ECP) has demonstrated therapeutic benefit in patients with Sézary syndrome (SS) and erythrodermic mycosis fungoides (e-MF). To examine the efficacy of ECP in the modern era of novel therapies, we conducted a retrospective analysis of 65 patients with a diagnosis of SS or e-MF with blood involvement who were treated with ECP at our institute. Overall survival (OS), time to next treatment (TTNT), and skin response rate (RR) were used as the study end points to determine patient outcome. The median follow-up from diagnosis was 48 months (range 1-225 months), with a median predicted OS of 120 months. The majority (88%) of patients commenced ECP at treatment lines 1 to 3, either as a monotherapy or in conjunction with other systemic agents. The use of ECP monotherapy resulted in a significantly longer median TTNT when compared with interferon-α (P = .0067), histone deacetylase inhibitors (P = .0003), novel immunotherapy agents (P = .028), low-dose methotrexate (P < .0001), and chemotherapy (P < .0001). In particular, early commencement of ECP at treatment lines 1 to 3 yielded a TTNT of 47 months. The results of our study support the utilization of ECP for SS/e-MF, and we recommend that ECP should be considered as early as possible in the treatment paradigm for these patients.

4.
Plast Reconstr Surg ; 143(3S A Review of Breast Implant-Associated Anaplastic Large Cell Lymphoma): 59S-64S, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30817557

RESUMO

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T-cell lymphoproliferative disorder occurring in patients with breast implants. Genomic characterization performed in BIA-ALCL to date has demonstrated qualitatively similar molecular abnormalities to those seen in its more common counterpart [ALK-negative systemic anaplastic large cell lymphoma (sALCL)] including JAK/STAT activation and MYC/TP53 dysregulation. Despite these observed similarities at the molecular level, the outcomes of sALCL and BIA-ALCL are markedly different with sALCL typically associated with an aggressive course and inferior outcomes compared with BIA-ALCL. This review describes the findings of high-throughput sequencing and other genomic characterization to date in BIA-ALCL and the insights these studies have given into the molecular drivers of this rare lymphoma subtype.


Assuntos
Quinase do Linfoma Anaplásico/genética , Implantes de Mama/efeitos adversos , Neoplasias da Mama/genética , Predisposição Genética para Doença , Linfoma Anaplásico de Células Grandes/genética , Adulto , Idoso , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Neoplasias da Mama/etiologia , Neoplasias da Mama/fisiopatologia , Feminino , Genômica , Humanos , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/fisiopatologia , Pessoa de Meia-Idade , Prognóstico
5.
Leuk Lymphoma ; 60(9): 2122-2133, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30777794

RESUMO

Efficacy and safety of bortezomib-based consolidation following ASCT were investigated in newly diagnosed multiple myeloma patients from Australia, Korea, and China. Patients received three cycles of bortezomib-cyclophosphamide-dexamethasone induction followed by high-dose therapy/ASCT, then were randomized (1:1) to consolidation with TP (thalidomide 100 mg/d for ≤12 months/until disease progression; prednisolone 50 mg on alternate days indefinitely/until disease progression; n = 100) or VTP (subcutaneous bortezomib 1.3 mg/m2 every 2 weeks for 32 weeks, plus TP; n = 103). The hypothesized difference in CR + VGPR rate (after ≤12 months consolidation therapy) was not met. The rate of CR + VGPR was numerically higher with VTP versus TP; however, this was not statistically significant (85.7% versus 77.1%; rate difference 8.6%; 95% confidence interval -2.3%-19.5%; p = .122). Secondary efficacy outcomes were similar between treatment arms. Addition of bortezomib to TP consolidation was associated with limited additional toxicity but did not significantly improve efficacy versus TP.

6.
Plast Reconstr Surg ; 143(5): 1285-1292, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30789476

RESUMO

BACKGROUND: The epidemiology and implant-specific risk for breast implant-associated (BIA) anaplastic large cell lymphoma (ALCL) has been previously reported for Australia and New Zealand. The authors now present updated data and risk assessment since their last report. METHODS: New cases in Australia and New Zealand were identified and analyzed. Updated sales data from three leading breast implant manufacturers (i.e., Mentor, Allergan, and Silimed) were secured to estimate implant-specific risk. RESULTS: A total of 26 new cases of BIA-ALCL were diagnosed between January of 2017 and April of 2018, increasing the total number of confirmed cases in Australia and New Zealand to 81. This represents a 47 percent increase in the number of reported cases over this period. The mean age and time to development remain unchanged. The implant-specific risk has increased for Silimed polyurethane (23.4 times higher) compared with Biocell, which has remained relatively static (16.5 times higher) compared with Siltex implants. CONCLUSIONS: The number of confirmed cases of BIA-ALCL in Australia and New Zealand continues to rise. The implant-specific risk has now changed to reflect a strong link to implant surface area/roughness as a major association with this cancer.


Assuntos
Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Austrália/epidemiologia , Implante Mamário/instrumentação , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/etiologia , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Poliuretanos/toxicidade , Complicações Pós-Operatórias/etiologia , Medição de Risco , Propriedades de Superfície , Adulto Jovem
7.
Int J Radiat Oncol Biol Phys ; 103(5): 1158-1166, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30553941

RESUMO

PURPOSE: The role of involved-field radiation therapy (IFRT) with autologous stem cell transplantation (ASCT) for lymphomas remains uncertain. METHODS AND MATERIALS: In this prospective, multicenter study, patients undergoing ASCT for relapsed/refractory lymphoma received peritransplant IFRT to disease sites identified at study registration (SR) (before salvage chemotherapy [SC]). Radiation dose was adapted to SC response. Survival, relapse rates/pattern, toxicity, and prognostic factors were evaluated. RESULTS: Forty-five patients were enrolled (23 with Hodgkin lymphoma, 22 with aggressive non-Hodgkin lymphoma). Three-year overall survival and cumulative incidence of posttransplant progression rates were 72% (95% confidence interval [CI], 59%-87%) and 42% (95% CI, 27%-57%), respectively. Stage (P = .03) and elevated lactate dehydrogenase (P = .05) were significant risk factors for disease progression on multivariable analysis. Three-year actuarial in-field, marginal, and distant progression rates were 7% (95% CI, 0%-15%), 9% (95% CI, 0%-18%), and 36% (95% CI, 21%-51%), respectively. Progression occurred in 8 of 30 patients with all sites irradiated and in 13 of 15 patients without all sites irradiated. There were 117 disease sites at SR and 64 post-ASCT progression sites, of which 15 were involved at SR and 12 only at initial diagnosis. Posttransplant relapse occurred in 3 of 83 irradiated and 12 of 34 unirradiated involved sites. Of 28 sites in complete response to SC on computed tomography, there was no relapse in any of the 21 irradiated sites and in 1 of 7 unirradiated sites. Of 72 sites in complete response on positron emission tomography, relapse occurred in 1 of 50 irradiated and 10 of 22 unirradiated sites. No grade 4 nonhematologic radiation therapy toxicities were observed. CONCLUSIONS: IFRT was well tolerated and associated with a low rate of in-field progression. Progression rates were lower for patients with all disease sites irradiated. Response to SC on both computed tomography and positron emission tomography warrants further study to select sites for IFRT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Intervalos de Confiança , Progressão da Doença , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Recidiva , Terapia de Salvação/métodos , Análise de Sobrevida , Transplante Autólogo , Falha de Tratamento
8.
Expert Rev Hematol ; 12(1): 5-19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30526166

RESUMO

INTRODUCTION: Brentuximab vedotin is an antibody-drug conjugate, which combines a CD30 monoclonal antibody with the microtubule-disrupting agent monomethylauristatin E. The utility of brentuximab vedotin has been explored in a number of diseases, with a recent focus on T-cell lymphoma, particularly systemic anaplastic large-cell lymphoma (sALCL) and cutaneous T-cell lymphoma (CTCL), as well as other peripheral T-cell lymphoma (PTCL) histologies. Areas covered: This review surveys current data on the efficacy of brentuximab vedotin in T-cell lymphoma, as well as embedding it in a therapeutic context by reviewing potential competitor agents in the clinic. Data are drawn from published literature, with a focus on clinical trial data rather than preclinical studies or case reports. Expert opinion: Brentuximab vedotin has a clear clinical benefit in CTCL and sALCL, and can achieve durable responses in a number of patients. Toxicities, particularly peripheral neuropathy, may limit treatment in some patients; however, the agent is generally well tolerated. In this context, brentuximab vedotin has been globally approved for use in sALCL and certain CTCL subtypes, however, further information is required to enhance our understanding of when and in whom to best employ this agent, as well as exploring rational combinations to augment responses.

10.
Nat Genet ; 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30429576

RESUMO

In the version of this article originally published, the main-text sentence "In three patients of European ancestry, we identified the germline variant encoding p.Ile97Met in TIM-3, which was homozygous in two (P12 and P13) and heterozygous in one (P15) in the germline but with no TIM-3 plasma membrane expression in the tumor" misstated the identifiers of the two homozygous individuals, which should have been P13 and P14. The error has been corrected in the HTML, PDF and print versions of the paper.

11.
Nat Genet ; 50(12): 1650-1657, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30374066

RESUMO

Subcutaneous panniculitis-like T cell lymphoma (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation that adversely affects survival1,2. T cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants altering highly conserved residues of TIM-3, c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met), each with specific geographic distribution. The variant encoding p.Tyr82Cys TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while p.Ile97Met TIM-3 occurs in patients with European ancestry. Both variants induce protein misfolding and abrogate TIM-3's plasma membrane expression, leading to persistent immune activation and increased production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, promoting HLH and SPTCL. Our findings highlight HLH-SPTCL as a new genetic entity and identify mutations causing TIM-3 alterations as a causative genetic defect in SPTCL. While HLH-SPTCL patients with mutant TIM-3 benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30345474

RESUMO

PURPOSE OF REVIEW: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognised malignancy of T lymphocytes exclusively associated with textured breast implants. This review aims to evaluate existing theories regarding the epidemiology, pathogenesis, clinical evaluation and management of the disease. RECENT FINDINGS: The true incidence of BIA-ALCL is difficult to define. Prevailing pathogenic theories recognise the interplay between textured implants, Gram-negative bacteria, host genetics (e.g. JAK/STAT, p53) and time. Patients typically present with a delayed seroma and less commonly with a capsular mass or systemic disease at an average of 8-10 years after implantation. BIA-ALCL staging has evolved from a "liquid tumour" model to a "solid tumour" classification. For localised disease, surgery involving complete capsulectomy and implant removal is the cornerstone of treatment. For more advanced disease, treatment includes surgery followed by chemotherapy (combination anthracycline-based), radiotherapy and the antibody drug conjugate (brentuximab vedotin). The interplay between the Gram-negative biofilm, implant texturing, genetic mutations and time has been implicated in pathogenesis of BIA-ALCL. The identification of a putative infectious cause is not unique to lymphomagenesis. Future research, investigating BIA-ALCL genetic mutations and immunological modulation with Gram-negative biofilm in BIA-ALCL models is warranted.

13.
Haematologica ; 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30237262

RESUMO

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow-up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow-up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P <0.0001). The overall response rate was 92.9% versus 76.4%, and 51.2% versus 21.0% achieved a complete response or better, respectively (both P <0.0001). At the 10e5 sensitivity threshold, 26.2% versus 6.4% were minimal residual disease-negative, respectively (P <0.0001). Post hoc analyses of clinical relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone versus lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all P <0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 vs 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; P = 0.0921) and patients with treatment-free intervals of >12 and ≤12 months, >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses versus lenalidomide/dexamethasone. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02076009.

14.
Curr Rheumatol Rep ; 20(10): 64, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30173305

RESUMO

PURPOSE OF REVIEW: Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy. RECENT FINDINGS: Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of "real world" data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important. Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients.

15.
Best Pract Res Clin Haematol ; 31(3): 322-335, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30213403

RESUMO

Novel systemic therapies are generally prescribed to patients with advanced-stage disease or those with early-stage disease refractory to skin-directed therapies. In general, systemic chemotherapy should be reserved for patients who fail to respond to biological agents. Such biological agents include interferon alfa, bexarotene, histone deacetylase inhibitors (vorinostat, romidepsin), brentuximab vedotin and mogamulizumab. Extracorporeal photopheresis is particularly effective for patients with Sézary Syndrome. Allogeneic transplantation is becoming increasing used for younger patients. Novel agents in advanced development include the monoclonal antibody IPH4102,duvelisib,and the new modified formulation of denileukin diftitox. The choice of agents for patients is typically a balance of patient factors (age, co-morbidities, geographic location), relative efficacy and toxicity.

16.
Australas J Dermatol ; 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29992535

RESUMO

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co-risk factors such as obesity. The increase in treatment-independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T-cell lymphoma is substantially higher in patients with moderate-to-severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co-risk factors. The risk of cancer from low-dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients' specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug-drug interaction with cancer-directed therapies, including radiotherapy.

17.
Expert Opin Investig Drugs ; 27(8): 691-697, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30001170

RESUMO

INTRODUCTION: Therapeutic options for mycosis fungoides and Sézary syndrome include a variety of immunomodulatory, epigenetic, and cytotoxic options; however, none has been demonstrated to be efficacious for all patients, or to deliver deep and durable responses to the majority of patients. In this review, we examine the monoclonal antibody, IPH4102, a novel agent for the treatment of cutaneous T-cell lymphoma. Areas covered: In this review, we examine data demonstrating the tissue specificity of KIR3DL2 receptor, which is highly expressed on the malignant cells in cutaneous T-cell lymphoma, including mycosis fungoides and Sézary syndrome. This specificity has led to the development of the agent IPH4102. Preclinical data showing efficacy of IPH4102 in vivo are outlined, as well as the results from Phase I clinical trials, which suggest that the agent is both efficacious and well-tolerated. Larger scale clinical trials are to follow. Expert Opinion: We examine the putative benefit of IPH4102 in comparison to established agents already in the clinic, highlighting its efficacy and relative safety. We also examine possible directions that may better define the role of IPH4102 in the treatment of T-cell lymphoma in the future.


Assuntos
Linfoma Cutâneo de Células T/tratamento farmacológico , Receptores KIR3DL2/imunologia , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Linfoma Cutâneo de Células T/imunologia
18.
J Clin Pathol ; 71(10): 895-899, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29760015

RESUMO

AIMS: Multiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre. METHODS: A cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline. RESULTS: At least one mutation was found in 69 (80%) patients. Frequently mutated genes included TP53 (36%), KRAS (22.1%), NRAS (15.1%), FAM46C/DIS3 (8.1%) and TET2/FGFR3 (5.8%), including multiple mutations not previously described in myeloma. Importantly we observed TP53 mutations in the absence of a 17 p deletion in 8% of the cohort, highlighting the need for sequencing-based assessment in addition to cytogenetics to identify these high-risk patients. Multiple novel copy number changes and immunoglobulin heavy chain translocations are also discussed. CONCLUSIONS: Our results demonstrate that many clinically relevant genomic findings remain in multiple myeloma which have not yet been identified through large-scale sequencing efforts, and provide important mechanistic insights into plasma cell pathobiology.


Assuntos
Mieloma Múltiplo/genética , Idoso , Aberrações Cromossômicas , Análise Mutacional de DNA/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Sci Rep ; 8(1): 4159, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29515123

RESUMO

Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protein 1 (MR1) antigen-presenting molecule. While MAIT cells are highly abundant in humans, their role in tumour immunity remains unknown. Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors. Furthermore, there was no evidence that MAIT cells accumulated at the disease site (bone marrow) of these patients. Newly diagnosed MM patient MAIT cells had reduced IFNγ production and CD27 expression, suggesting an exhausted phenotype, although IFNγ-producing capacity is restored in relapsed/refractory patient samples. Moreover, immunomodulatory drugs Lenalidomide and Pomalidomide, indirectly inhibited MAIT cell activation. We further show that cell lines can be pulsed with vitamin-B derivative Ags and that these can be presented via MR1 to MAIT cells in vitro, to induce cytotoxic activity comparable to that of natural killer (NK) cells. Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies.

20.
Oncotarget ; 9(15): 11887-11888, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29552279
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