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1.
Recent Results Cancer Res ; 214: 71-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473849

RESUMO

Bispecific T cell engagers are antibody constructs directed to a tumor-specific target on the one hand and to CD3-positive T cells on the other hand. Blinatumomab is a compound with specificity for the pan-B cell marker CD19. Clinical activity was tested in relapsed and refractory (R/R) non-Hodgkin's Lymphoma (NHL), R/R acute lymphoblastic leukemia (ALL), and ALL patients with minimal residual disease. Trials have already been started in de novo ALL. The most clinically relevant toxicities are neurologic events and cytokine release syndrome as with other T cell-activating therapies. The mechanisms of resistance are not fully understood. Higher leukemia load and later stage disease represent unfavorable factors. Besides, an upregulation of regulatory T cells and inhibitory molecules like PD-1/PD-L1 may have a role as the loss of target by several mechanisms. The future will show whether the use of bispecifics in ALL can change the standard treatment algorithms and whether bispecific T cell engagers will also be successfully used in other malignant entities.


Assuntos
Anticorpos Biespecíficos/farmacologia , Linfoma não Hodgkin/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/citologia , Antígenos CD19 , Ensaios Clínicos como Assunto , Humanos , Neoplasia Residual/terapia
2.
Hautarzt ; 70(10): 815-830, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31511903

RESUMO

Cutaneous lymphomas comprise different subgroups with distinct biological behavior. Mycosis fungoides, the most common cutaneous lymphoma, presents with patches, plaques, tumors and erythroderma. Therapeutic options depend on stage and comprise local skin-directed treatment in early stages, while later stages and Sézary syndrome require systemic therapies including bexarotene, interferon or brentuximab vedotin. While the rare CD4-positive lymphoproliferation and acral CD8-positive lymphoma present with an invariably indolent course, cutaneous peripheral T­cell lymphomas exhibit an aggressive clinical behavior. Among the subgroup of cutaneous B­cell lymphomas, primary cutaneous marginal zone lymphoma and follicle center cell lymphoma belong to indolent entities with almost unrestricted overall survival, whereas cutaneous large B­cell lymphoma presents with a significant risk of systemic dissemination and is associated with high lethality.


Assuntos
Linfoma de Células B/terapia , Linfoma não Hodgkin/terapia , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/terapia , Micose Fungoide/diagnóstico , Micose Fungoide/terapia , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Linfoma , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Linfoma Cutâneo de Células T/mortalidade , Micose Fungoide/mortalidade , Síndrome de Sézary/mortalidade , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida
3.
Medicine (Baltimore) ; 98(26): e16129, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261533

RESUMO

Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.


Assuntos
Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/terapia , Adulto , Antineoplásicos/uso terapêutico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/patologia , Linfoma de Burkitt/terapia , Feminino , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos
4.
Oncology ; 97(2): 59-74, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261152

RESUMO

Chimeric antigen receptor (CAR) modified T-cell therapy, a unique platform technology highlighting precision medicine through utilization of molecular biology and cell-based therapeutics has shown unprecedented rates in patients with hematological malignancies such as acute lymphocyte leukemia, non-Hodgkin's lymphoma and multiple myeloma (MM). With the approval of CD19-targeted CAR T-cells by the Food and Drug Administration in acute lymphoblastic leukemia (ALL) and NHL, this technology is positioned for aggressive expansion to combination therapeutic opportunities and proof of principle towards utility in other malignant disorders. However, despite the impressive results seen with hematological malignancies, CAR T-cells have shown limited efficacy in solid tumors with several unsuccessful preclinical studies. Regardless, these attempts have provided us with a better understanding of the imminent challenges specific to solid tumors even if they have not so far led to expanded clinical treatment opportunities outside ALL/NHL/MM. This review summarizes our current understanding of CAR T-cell mechanism of action, while presenting the major limitations of CAR T-cell derived treatments in solid tumors. We further discuss recent findings and present new potential strategies to overcome the challenges facing solid tumor targeting by CAR T-cell platforms.


Assuntos
Imunoterapia Adotiva , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/imunologia , Antígenos CD19/imunologia , Humanos , Estudo de Prova de Conceito
5.
Hematol Oncol ; 37 Suppl 1: 70-74, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187522

RESUMO

ctDNA provides an important new strategy that will aid in the treatment of non-Hodgkin's lymphoma. Immunoglobulin sequencing provides a tumor specific marker for disease activity with a sensitivity equivalent to one tumor cell per 10-6. Furthermore, it can provide an estimate of tumor bulk and tumor response dynamics during treatment. Interim monitoring can identify patients at high risk of treatment failure and surveillance monitoring can identify patients months before radiographic disease progression. Tumor specific mutations can also be detected in ctDNA and may reflect an averaging of mutations present within multiple tumor masses. Such analysis may aid in the molecular characterization of tumors and selection of targeted treatments for precision medicine.


Assuntos
Biópsia Líquida , Linfoma não Hodgkin/diagnóstico , Biomarcadores Tumorais , DNA Tumoral Circulante , Humanos , Biópsia Líquida/métodos , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/terapia , Técnicas de Diagnóstico Molecular , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia
6.
Rinsho Ketsueki ; 60(3): 165-170, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31068511

RESUMO

Failure of autologous peripheral blood stem cell collection (PBSCH) can affect the treatment modality for patients with hematological malignancies. The clinical efficacy of plerixafor in PBSCH was analyzed in our institution. The medical records of 61 patients were retrospectively reviewed. The use of plerixafor was determined according to the CD34+ cell count in the peripheral blood (PB CD34+) on day 4 of G-CSF administration and patients' backgrounds. A total of 47 patients received G-CSF plus plerixafor: 31 with multiple myeloma, 8 with AL amyloidosis or POEMS syndrome, and 8 with non-Hodgkin lymphoma. The median fold increase in PB CD34+ following the first dose of plerixafor was 7.18 times. The median number of collected CD34+ cells on day 5 was 4.1×106/kg and 5.3×106/kg in total. Among the 47 patients, 44 (93.6%) yielded the minimum required cell collection of 2.0×106/kg within an average of 1.3 days. Plerixafor enables rapid and efficient mobilization, and sufficient numbers of CD34+ cells were successfully collected.


Assuntos
Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Células-Tronco de Sangue Periférico/citologia , Amiloidose/terapia , Antígenos CD34 , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Síndrome POEMS/terapia , Estudos Retrospectivos , Transplante Autólogo
7.
Ann Hematol ; 98(7): 1743-1753, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31089793

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still considered a definitive curative modality for refractory or relapsed non-Hodgkin's lymphoma (NHL). However, transplant-related morbidity and mortality remain a considerable challenge. The graft-versus-host disease (GVHD)-free with relapse-free survival (GRFS) rate and GRFS-related prognostic factors have not been fully examined for NHL alone. We evaluated 104 consecutive patients with refractory or relapsed aggressive NHL receiving allo-HSCT at a single institution. With a median follow-up of 31.5 months, the estimated 3-year overall survival (OS), disease-free survival (DFS), the cumulative incidence rates of relapse, and non-relapse mortality were 45.9%, 45.9%, 36.0%, and 17.0%, respectively. The patients with overall grades III-IV acute GVHD had markedly inferior OS and DFS (p = 0.040 for OS and p = 0.028 for DFS). However, patients with more than mild stage chronic GVHD showed superior OS and DFS (p = 0.004 and p = 0.008, respectively). The 1- and 3-year GRFS rates were 44.5% and 36.9%, respectively. The negative bone marrow involvement at diagnosis, chemosensitive disease status, and fewer exposure lines of chemotherapy before transplantation significantly increased the GRFS incidence. However, no transplant-associated factors were related to GRFS incidence. Furthermore, applying dynamic GRFS method which excepted patients whose chronic GVHD was fully resolved within short-period, survival rate significantly increased over time (36.9% vs. 41.9%, p = 0.045 for conventional GRFS vs. dynamic GRFS at 3 years after transplantation). In conclusion, these results suggest that GRFS is also a useful endpoint to assess transplant outcomes, and the dynamic GRFS calculation, including rapidly manageable chronic GVHD, is a more practical method for patients with refractory or relapsed heterogenous subtypes of NHL.


Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
8.
Chemotherapy ; 64(1): 36-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31117081

RESUMO

BACKGROUND: Fertility and gonadal function represent one of the most important aspects for long-term lymphoma survivors. AIMS: The aim of our study was to determine possible risk factors, such as age at treatment, chemotherapeutic regimen, protection with oral contraceptives (OCs), and gonadotropin-releasing hormone (GnRH) analogues in female patients treated for Hodgkin's lymphoma (HL) or non-Hodgkin lymphoma (NHL) at a reproductive age. METHODS: Patients between the age of 16 and 50 years at the time of HL or NHL diagnosis were selected. Eligible patients were requested to respond to a questionnaire by phone interview about fertility, menstrual status, sexual aspects, and treatment with OCs or GnRH analogues during chemotherapy. RESULTS: The resumption of menstrual activity was associated with the use of the OCs and GnRH analogues during chemotherapy (p = 0.008 and 0.034, respectively). At univariate analysis, the use of OCs during chemotherapy was associated with a lower risk of amenorrhea (prevalence ratio [PR] = 0.37; 95% CI 0.17-0.82). A higher age at the time of treatment correlated positively with therapy-induced amenorrhea, with a difference of 12.8 years between the mean age at diagnosis of the women with therapy-induced amenorrhea and those who resumed their menses. Amenorrhea was significantly higher in women receiving R-CHOP than in women treated with ABVD (PR = 6.00; 95% CI 2.32-15.54). Moreover, NHL had an infertility PR of 1.51 (95% CI 0.86-2.45) at multivariate analysis compared to HL. CONCLUSIONS: This study suggests a possible role of pharmacological prophylaxis with OCs and GnRH analogues.


Assuntos
Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Administração Oral , Adolescente , Adulto , Amenorreia/tratamento farmacológico , Amenorreia/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticoncepcionais/farmacologia , Anticoncepcionais/uso terapêutico , Feminino , Fertilidade/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Adulto Jovem
9.
Medicine (Baltimore) ; 98(11): e14805, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882658

RESUMO

RATIONALE: This article describes the case of a patient with 2 simultaneous malignant diseases: Follicular lymphoma and 'castration sensitive prostate cancer. Patients with multiple cancers are not easy to manage and it is difficult to find the appropriate approach and resources to use with them. We focused our attention on how to choose the correct strategy to face 2 different neoplasms and control the adverse reactions related to the corresponding treatments. PATIENT CONCERNS: We present a case of a 71-year-old man who came to us complaining about an abnormal difficulty in urinating associated with an interrupted flow and excessive urination at night. Clinical examination detected multiple enlarged superior and inferior diaphragmatic lymph nodes. DIAGNOSIS: Prostate biopsy revealed an acinar adenocarcinoma (Gleason 4+3, Grade group 3). Clinical staging by bone scan was negative but computed tomography scan (CT) detected multiple enlarged superior and inferior diaphragmatic, and inguinal lymph nodes. This type of lymph node involvement pattern is unusual for an acinar adenocarcinoma prostate cancer therefore we suspected the simultaneous presence of a lymphatic neoplasm. Fluorodeoxyglucose positron emission tomography scan. The exam showed one of the left inguinal lymph nodes had the highest standardized uptake value (13.0) so a biopsy was taken. The sample analysis confirmed the diagnosis of a follicular non-Hodgkin lymphoma of Grade 3a. INTERVENTIONS: We used a multidisciplinary clinical approach based on Rituximab+CHOP administered every 21 days. Simultaneously, the patient underwent androgen deprivation therapy with triptorelin monthly and bicalutamide administered just during the first month of treatment. When we obtained a complete response for the lymphoma, the patient continued the therapy with Rituximab once every 2 months for the next 2 years. Then we added volumetric modulated arc therapy (VMAT) radiotherapy with simultaneous integrated boost (SIB) to androgen deprivation therapy for the duration of 1 month. OUTCOMES: After 1 year and 6 months since the conclusion of therapy for prostate cancer and Follicular lymphoma, patient's conditions are good and he is in complete remission for both diseases. Gut toxicity is reduced with a mean number of 2 to 3 discharges daily and an increased body weight. LESSONS: The presence of diffuse lymphadenopathy and urinary symptoms in the same patients must induce the suspect of 2 contemporary cancer diseases. Parallel treatments of follicular lymphoma and prostate cancer should consider the increased risk of severe adverse effects related to the treatment and their management. We describe our therapeutic strategy to highlight the importance to balance benefits and disadvantages to get the best possible response and maintain a good quality of life in this complex setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Acinares , Linfonodos/patologia , Linfoma não Hodgkin , Próstata/patologia , Neoplasias da Próstata , Rituximab/administração & dosagem , Pamoato de Triptorrelina/administração & dosagem , Idoso , Antineoplásicos Hormonais/administração & dosagem , Biópsia/métodos , Carcinoma de Células Acinares/patologia , Carcinoma de Células Acinares/fisiopatologia , Carcinoma de Células Acinares/terapia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Fluordesoxiglucose F18/farmacologia , Humanos , Achados Incidentais , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Tomografia por Emissão de Pósitrons/métodos , Prednisona/administração & dosagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/terapia , Compostos Radiofarmacêuticos/farmacologia , Radioterapia de Intensidade Modulada/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Vincristina/administração & dosagem
10.
Crit Rev Oncol Hematol ; 135: 8-19, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30819450

RESUMO

Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments.


Assuntos
Linfoma não Hodgkin , Adulto , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino
12.
Future Oncol ; 15(11): 1197-1205, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30730219

RESUMO

The decisive factor in selecting a treatment regimen for a frail patient with aggressive non-Hodgkin's lymphoma is identifying whether a patient is fit enough to tolerate curative-intent anthracycline-containing regimens or too frail and therefore at risk of being undertreated. As cardiac comorbidities are an important contributor to both the health status and the selection of treatment, cardiovascular profiling and baseline risk stratification prior to treatment should be considered. Comprehensive geriatric assessment is an efficient means of identifying elderly patients with non-Hodgkin's lymphoma who may benefit from a curative treatment approach. If anthracycline-based therapy is not suitable, alternative treatment options are available in frail patients with cardiac comorbidities, but these must be adjusted to the patient's health status to achieve a maximal benefit-risk ratio.


Assuntos
Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comorbidade , Gerenciamento Clínico , Idoso Fragilizado , Humanos , Linfoma não Hodgkin/epidemiologia , Gradação de Tumores
13.
Int J Hematol ; 109(3): 260-277, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30671909

RESUMO

Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin lymphoma (NHL) with an aggressive course and worse outcomes compared with other lymphomas of similar tumor burden and histologic subtype. High-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT) is an option for therapy for this disease in both the relapse setting and as post-remission consolidation. Data are currently limited to only several single-arm phase II trials with small sample sizes, but randomized trials are now ongoing. In this review, we discuss the efficacy, feasibility, and toxicity of HDC/ASCT for PCNSL and its role in the treatment of this aggressive malignancy, both in the first-line and relapse settings. We also bring to attention the current data on allogeneic stem cell transplantation (allo-SCT) in PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Autoenxertos , Ensaios Clínicos Fase II como Assunto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Orphanet J Rare Dis ; 14(1): 9, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626415

RESUMO

BACKGROUND: Chylothorax is a rare condition which can be associated with malignant lymphoproliferative disorders (LPDs). We retrospectively analyzed the results of the conservative treatment of 10 patients with persistent non-traumatic malignant chylothorax. RESULTS: Conservative treatment lead to a decline of chylothorax after mean of 66 days and consisted of the treatment of the underlying disease and of simultaneous long-term supportive care (drainage of the thoracic cavity, dietary measures and nutrition management). In most cases (80%), chylothorax disappeared only after a successful therapeutic response of the underlying disease. Low-dose radiotherapy had very good effects in two patients. CONCLUSION: Conservative treatment of malignant chylothorax can be considered a suitable method. Based on our results, successful treatment of the lymphoproliferative disorder seems to be a very important factor for the disappearance of chylothorax.


Assuntos
Quilotórax/radioterapia , Quilotórax/terapia , Transtornos Linfoproliferativos/radioterapia , Transtornos Linfoproliferativos/terapia , Idoso , Quilotórax/tratamento farmacológico , Feminino , Humanos , Leucemia Linfoide/tratamento farmacológico , Leucemia Linfoide/radioterapia , Leucemia Linfoide/terapia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Linfoma não Hodgkin/terapia , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ducto Torácico/efeitos dos fármacos , Ducto Torácico/efeitos da radiação
15.
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
16.
BMC Vet Res ; 14(1): 306, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305106

RESUMO

BACKGROUND: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions. RESULTS: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. CONCLUSIONS: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine.


Assuntos
Doenças do Gato/patologia , Modelos Animais de Doenças , Linfoma não Hodgkin/veterinária , Linfoma de Células T Periférico , Animais , Doenças do Gato/diagnóstico , Doenças do Gato/terapia , Gatos , Sistema Digestório/patologia , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/veterinária , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia
17.
J Cancer Res Ther ; 14(5): 926-933, 2018 Jul-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30197327

RESUMO

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the treatment of choice for patients with relapsed and refractory (RR) lymphoma. We analyzed toxicity and long-term outcome with lomustine, cytarabine, cyclophosphamide, etoposide (LACE) conditioning in patients with primary refractory or relapsed lymphoma undergoing autologous transplant. Materials and Methods: One-hundred patients with primary refractory (23), chemotherapy sensitive relapse (74) or RR (3) Hodgkin lymphoma (HL - 70 patients), and non-HL (NHL - 30 patients) underwent HSCT with LACE (lomustine 200 mg/m 2 day-7, etoposide 1000 mg/m 2 day-7, cytarabine 2000 mg/m 2 day-6 to day-5, and cyclophosphamide 1800 mg/m 2 day-4 to day-2) conditioning between November 2007 and December 2013. At transplant, 68 patients were in complete remission (CR), 29 in partial remission, 2 had stable disease, and 1 had progressive disease. Patients were followed up for development of transplant-related toxicities and long-term survival outcome. Results: The incidence of grades 3-4 oral mucositis and grades 3-4 diarrhea was 8% and 4%, respectively. Median days to myeloid and platelet engraftment were 10 and 13. Transplant-related mortality was 7%. At median follow-up of 3 years, probability of overall survival (OS) and progression-free survival (PFS) at 3 years was 70% and 58% in entire cohort, 78% and 62% in HL and 51% and 46% in NHL subgroup, respectively. International Prognostic Score (IPS) >2 at relapse prognosticated for poor OS (P = 0.002) and PFS (P < 0.001) in HL subgroup. Positron emission tomography positivity pretransplant (HL subgroup) and at day + 100 (NHL subgroup) predicted for poor survival. Conclusion: We conclude that LACE is effective and well-tolerated conditioning regimen. IPS at relapse is the most important prognostic factor in HL transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Recidiva Local de Neoplasia/terapia , Prognóstico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Lomustina/administração & dosagem , Linfoma/patologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva , Indução de Remissão , Condicionamento Pré-Transplante , Transplante Autólogo , Adulto Jovem
20.
Indian J Cancer ; 55(1): 9-15, 2018 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30147087

RESUMO

Introduction: There is paucity of data from India about the outcomes of patients with various hematological malignancies. Since its formation in 2009, the adult hematolymphoid disease management group of the Tata Memorial Centre is dedicated to the treatment of hematological malignancies alone. In this report, we present the outcomes of patients treated at our centre over a 5 year period for various haematological malignancies in both transplant and non-transplant setting. Methods: This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated at our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016. Results: Overall, 1869, 3633 and 544 patients with acute leukemias, various lymphomas and myeloma respectively were registered at our centre from 1st January 2010 to 31st December 2014. Of these, 1178 (63%), 3091 (85%) and 454 (83%) respectively received treatment at our centre. The cumulative probability of 5 year overall survival for patients with acute leukemias, Hodgkin's lymphoma, non-Hodgkin lymphoma and myeloma treated at our centre is 40%, 85%, 78% and 40% respectively. Four hundred and fifteen stem cell transplants were done between 14th November 2007 to 31st December 2014 with 46% being allogeneic and 54% being autologous. The 5 year overall survival of patients with allogenic and autologous transplant was 52% and 63% respectively. Conclusions: This is the largest single centre data on outcomes of various haematological malignancies from India. This real world data identifies areas which need further attention to improve outcomes.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco , Transplante Autólogo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Índia/epidemiologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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