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1.
Br J Haematol ; 175(5): 876-883, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27681999

RESUMEN

Involvement of the internal female reproductive organs by diffuse large B-cell lymphoma (DLBCL) is uncommon, and there are sparse data describing the outcomes of such cases. In total, 678 female patients with DLBCL staged with positron emission tomography/computed tomography and treated with rituximab-containing chemotherapy were identified from databases in Denmark, Great Britain, Australia, and Canada. Overall, 27/678 (4%) had internal reproductive organ involvement: uterus (n = 14), ovaries (n = 10) or both (n = 3). In multivariate analysis, women with uterine DLBCL experienced inferior progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system (CNS) involvement (SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL) and 0/10 women with ovarian DLBCL without concomitant uterine involvement. In multivariate analysis adjusted for other risk factors for SCNS, uterine involvement by DLBCL remained strongly associated with SCNS (Hazard ratio 14·13, 95% confidence interval 5·09-39·25, P < 0·001). Because involvement of the uterus by DLBCL appears to be associated with a high risk of SCNS, those patients should be considered for CNS staging and prophylaxis. However, more studies are needed to determine whether the increased risk of secondary CNS involvement also applies to women with localized reproductive organ DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso/patología , Neoplasias Uterinas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/secundario , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Pronóstico , Estudios Retrospectivos , Rituximab/uso terapéutico , Tasa de Supervivencia , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/mortalidad , Neoplasias Uterinas/patología , Adulto Joven
3.
Ugeskr Laeger ; 181(10)2019 Mar 04.
Artículo en Danés | MEDLINE | ID: mdl-30869069

RESUMEN

Cancer immune therapy is now used routinely for the treatment of several solid malignancies, albeit just recently having entered the clinic for treatment of haematological malignancies. Several studies demonstrate that cancer immune therapy is a promising treatment modality for the latter. Especially treatment with chimeric antigen receptor T cells for acute lymphoblastic leukaemia and lymphoma is promising. Other promising treatment modalities are immune check point inhibitors for both lymphoid and myeloid malignancies, as well as therapeutic cancer vaccination targeting tumour antigens.


Asunto(s)
Neoplasias Hematológicas , Inmunoterapia , Trastornos Mieloproliferativos , Antígenos de Neoplasias , Neoplasias Hematológicas/terapia , Humanos
4.
Front Immunol ; 9: 2264, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30327655

RESUMEN

Peptides vaccination is an interesting approach to activate T-cells toward desired antigens in hematological malignancies. In addition to classical tumor associated antigens, such as cancer testis antigens, new potential targets for peptide vaccination comprise neo-antigens including JAK2 and CALR mutations, and antigens from immune regulatory proteins in the tumor microenvironment such as programmed death 1 ligands (PD-L1 and PD-L2). Immunosuppressive defenses of tumors are an important challenge to overcome and the T cell suppressive ligands PD-L1 and PD-L2 are often present in tumor microenvironments. Thus, PD-L1 and PD-L2 are interesting targets for peptide vaccines in diseases where the tumor microenvironment is known to play an essential role such as multiple myeloma and follicular lymphoma. In myelodysplastic syndromes the drug azacitidine re-exposes tumor associated antigens, why vaccination with related peptides would be an interesting addition. In myeloproliferative neoplasms the JAK2 and CALR mutations has proven to be immunogenic neo-antigens and thus possible targets for peptide vaccination. In this mini review we summarize the basis for these novel approaches, which has led to the initiation of clinical trials with various peptide vaccines in myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and follicular lymphoma.


Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Terapia Molecular Dirigida/métodos , Vacunas de Subunidad/uso terapéutico , Antígenos de Neoplasias/inmunología , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Humanos , Linfoma Folicular/inmunología , Linfoma Folicular/terapia , Proteína 2 Ligando de Muerte Celular Programada 1/inmunología , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral/inmunología
5.
Eur J Cancer ; 93: 57-68, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29477102

RESUMEN

PURPOSE: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. METHODS: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. RESULTS: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). CONCLUSIONS: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/patología , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
6.
Eur J Cancer ; 75: 195-203, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28237865

RESUMEN

PURPOSE: Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. METHODS: We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. RESULTS: Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2-21.2%) compared with 2.6% (95% CI 1.7-3.5) among those with ≤2 sites (P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. CONCLUSIONS: Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Inmunoterapia/métodos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Recurrencia Local de Neoplasia/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/prevención & control , Neoplasias del Sistema Nervioso Central/secundario , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos , Linfoma de Células B Grandes Difuso/prevención & control , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/administración & dosificación , Estudios Retrospectivos , Factores de Riesgo , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto Joven
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