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1.
J Clin Med ; 10(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800409

RESUMO

Hodgkin lymphoma (HL) is a rare malignancy accounting for roughly 15% of all lymphomas and mostly affecting young patients. A second peak is seen in patients above 60 years of age. The history of HL treatment represents a remarkable success story in which HL has turned from an incurable disease to a neoplasm with an excellent prognosis. First-line treatment with stage-adapted treatment consisting of chemotherapy and/or radiotherapy results in cure rates of approximately 80%. Second-line treatment mostly consists of intensive salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Novel approaches such as antibody drug conjugates and immunomodulatory drugs have shown impressive results in clinical trials in refractory and relapsed HL and are now increasingly implemented in earlier treatment lines. This review gives a comprehensive overview on HL addressing epidemiology, pathophysiology and current treatment options as well as recent developments and perspectives.

2.
Lancet Haematol ; 8(4): e278-e288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770483

RESUMO

BACKGROUND: To improve the long-term tumour control in early, unfavourable Hodgkin Lymphoma, the German Hodgkin Study Group (GHSG) HD14 trial compared four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with an intensified chemotherapy regimen consisting of two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus two cycles of ABVD. The final analysis of the trial showed a significant advantage in terms of freedom from treatment failure (difference 7·2% [95% CI 3·8-10·5] at 5 years) for patients who received two cycles of escalated BEACOPP and two cycles of ABVD. However, there was no difference in overall survival between the two groups. To evaluate long-term efficacy and toxicity of this strategy, we did a follow-up analysis. METHODS: Patients aged 18-60 years with performance status of 2 or less and primary diagnosis of early, unfavourable Hodgkin lymphoma (all histologies) were included in an international, randomised, open-label, phase 3 trial. Patients were randomly assigned to receive four cycles of ABVD (ABVD group) or two cycles of escalated BEACOPP and two cycles of ABVD (2 + 2 group), both groups also received 30 Gy involved field radiotherapy. The ABVD dosing regimen was doxorubicin 25 mg/m2 (days 1 and 15), bleomycin 10 mg/m2 (days 1 and 15), vinblastine 6 mg/m2 (days 1 and 15), and dacarbazine 375 mg/m2 (days 1 and 15), repeated on day 29. The escalated BEACOPP dosing regimen was cyclophosphamide 1250 mg/m2 (day 1), doxorubicin 35 mg/m2 (day 1), etoposide 200 mg/m2 (days 1-3), procarbazine 100 mg/m2 (days 1-7), prednisone 40 mg/m2 (days 1-14), vincristine 1·4 mg/m2 (day 8; maximum 2 mg), and bleomycin 10 mg/m2 (day 8), repeated on day 22. After closure of the ABVD group according to prespecified rules, patients were assigned to receive two cycles of escalated BEACOPP and two cycles of ABVD (non-randomised 2 + 2 group), which continued until the end of the predefined 5-year recruitment period. In this prespecified long-term follow-up analysis, we aimed to evaluate the secondary endpoints progression-free survival, overall survival, and long-term toxicity. To this end, we did a descriptive intention-to-treat analysis of all qualified HD14 patients and on the predefined subsets of randomised qualified HD14 patients and patients in the non-randomised 2 + 2 group. The trial was registered on the International Standard Randomised Controlled Trial database, 04761296. FINDINGS: Between Jan 28, 2003, and Dec 29, 2009, 1686 patients were randomly assigned to the ABVD group (847 [50·2%] patients) and the 2 + 2 group (839 [49·8%] patients). 370 additional patients were recruited to the non-randomised 2 + 2 group. 1550 (92%) randomly assigned patients (median observation time 112 months [IQR 80-132]) and 339 (92%) patients in the non-randomised 2 + 2 group (median observation time 74 months [58-100]) were included in the qualified analysis set. 10-year overall survival in the randomly assigned patients was 94·1% (95% CI 92·0-95·7) for the ABVD group and 94·1% (91·8-95·7) for the 2 + 2 group (HR 1·0 [95% CI 0·6-1·5]; p=0·88). 8-year overall survival in the non-randomised 2 + 2 group was 95·1% (95% CI 91·6-97·2). 10-year progression-free survival in the randomly assigned patients was 85·6% (95% CI 82·6-88·1) for the ABVD group and 91·2% (88·4-93·3) for the 2 + 2 group (HR 0·5% [95% CI 0·4-0·7]; p=0·0001), accounting for a significant difference of 5·6% (95% CI 1·9-9·2) favouring the 2 + 2 group (p=0·0001). In the non-randomised 2 + 2 group, 8-year progression-free survival was 94·5% (95% CI 91·1-96·6). Standardised incidence ratios of second primary malignancies were similar between the ABVD group (2·3 [95% CI 1·6-3·1]) and the 2 + 2 group (2·5 [1·8-3·4]; Gray's p=0·80). Standardised incidence ratio of second primary malignancies was 3·1 (95% CI 1·7-5·0) in the non-randomised 2 + 2 group. INTERPRETATION: This long-term analysis confirms superior tumour control in the 2 + 2 group compared with the ABVD group without translating into an overall survival difference. At longer follow-up, there is no difference regarding second primary malignancies between groups. In conclusion, the 2 + 2 regimen spares a significant number of patients from the burden of relapse and additional treatment without increased long-term toxicity. FUNDING: Deutsche Krebshilfe eV and Swiss Federal Government.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Alemanha/epidemiologia , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Segunda Neoplasia Primária/epidemiologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Intervalo Livre de Progressão , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vincristina/administração & dosagem , Vincristina/uso terapêutico
3.
Br J Haematol ; 2021 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33486762

RESUMO

Data on non-Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first-line treatment within the randomized German Hodgkin Study Group (GHSG) HD7-HD15 studies. After a median follow-up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five-year event-free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death.

5.
Viruses ; 12(9)2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32962125

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global health emergency. To improve the understanding of the systemic component of SARS-CoV-2, we investigated if viral load dynamics in plasma and respiratory samples are associated with antibody response and severity of coronavirus disease 2019 (COVID-19). SARS-CoV-2 RNA was found in plasma samples from 14 (44%) out of 32 patients. RNAemia was detected in 5 out of 6 fatal cases. Peak IgG values were significantly lower in mild/moderate than in severe (0.6 (interquartile range, IQR, 0.4-3.2) vs. 11.8 (IQR, 9.9-13.0), adjusted p = 0.003) or critical cases (11.29 (IQR, 8.3-12.0), adjusted p = 0.042). IgG titers were significantly associated with virus Ct (Cycle threshold) value in plasma and respiratory specimens ((ß = 0.4, 95% CI (confidence interval, 0.2; 0.5), p < 0.001 and ß = 0.5, 95% CI (0.2; 0.6), p = 0.002). A classification as severe or a critical case was additionally inversely associated with Ct values in plasma in comparison to mild/moderate cases (ß = -3.3, 95% CI (-5.8; 0.8), p = 0.024 and ß = -4.4, 95% CI (-7.2; 1.6), p = 0.007, respectively). Based on the present data, our hypothesis is that the early stage of SARS-CoV-2 infection is characterized by a primary RNAemia, as a potential manifestation of a systemic infection. Additionally, the viral load in plasma seems to be associated with a worse disease outcome.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , RNA Viral/sangue , Idoso , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Feminino , Alemanha/epidemiologia , Hospitalização , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , RNA Viral/análise , Sistema Respiratório/virologia , Índice de Gravidade de Doença , Carga Viral , Viremia/sangue , Viremia/patologia , Viremia/virologia
6.
Blood ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32877522

RESUMO

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with distinct pathological and clinical characteristics. Unlike the malignant cells in classical Hodgkin lymphoma, the disease-defining lymphocyte predominant cells in NLPHL are consistently positive for CD20 but do not express CD30. The clinical course of NLPHL is indolent in the majority of cases. Most patients present with early-stage disease at initial diagnosis. First-line treatment for stage IA NLPHL usually consists of limited-field radiotherapy (RT) alone. Patients with early-stage NLPHL other than stage IA and intermediate-stage disease mostly receive combined-modality treatment whereas individuals with advanced NLPHL are treated with chemotherapy alone. In relapsed NLPHL, conventional chemotherapy, anti-CD20 antibodies and RT represent active treatment modalities. Only patients with poor-risk characteristics such as early disease recurrence are candidates for aggressive salvage treatment with high-dose chemotherapy and autologous stem cell transplantation. The overall and relative survival of patients with NLPHL is excellent as indicated by a low excess mortality in comparison with the general population. In this article, we discuss treatment options for patients with NLPHL and factors that influence the choice of therapy on the basis of the available data and two clinical cases.

7.
Nat Commun ; 11(1): 2465, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424289

RESUMO

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD+ LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD+ B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD+ DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD+ BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies.


Assuntos
Antígenos de Bactérias/imunologia , Linfócitos B/imunologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/microbiologia , Moraxella catarrhalis/imunologia , Adolescente , Adulto , Idoso , Autoantígenos/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Criança , RNA Polimerases Dirigidas por DNA/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Doença de Hodgkin/sangue , Humanos , Imunoglobulina D/metabolismo , Fragmentos Fab das Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Receptores de Antígenos de Linfócitos B/metabolismo
8.
Mycoses ; 63(6): 528-534, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32339350

RESUMO

OBJECTIVES: Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID-19) associated invasive aspergillosis at a single centre in Cologne, Germany. METHODS: A retrospective chart review of all patients with COVID-19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. RESULTS: COVID-19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. CONCLUSION: Clinicians caring for patients with ARDS due to COVID-19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co-infection.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Aspergilose Pulmonar/complicações , /complicações , Idoso , Antifúngicos/uso terapêutico , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/virologia , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Alemanha , Hemorragia/etiologia , Hospitais de Ensino , Humanos , Unidades de Terapia Intensiva , Pneumopatias/etiologia , Masculino , Mananas/análise , Metapneumovirus/isolamento & purificação , Pessoa de Meia-Idade , Nitrilos/uso terapêutico , Pandemias , Infecções por Paramyxoviridae/etiologia , Pneumonia Viral/diagnóstico por imagem , Aspergilose Pulmonar/diagnóstico por imagem , Piridinas/uso terapêutico , Estudos Retrospectivos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Triazóis/uso terapêutico , Voriconazol/uso terapêutico
9.
Pathology ; 52(1): 142-153, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31785822

RESUMO

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an unusual subtype of Hodgkin lymphoma characterised by a distinct histopathological and clinical presentation. It mostly affects males and presents with localised disease and an indolent clinical course in the majority of cases. However, there are also patients with advanced NLPHL who frequently present with spleen and liver involvement, B-symptoms and a more aggressive clinical course. Different clinical presentations correlate with distinct histopathological characteristics. NLPHL can be divided into typical and variant histopathological growth patterns. The clinical course of most patients with a typical growth pattern is indolent whereas patients with a variant histology more often present with advanced stage disease and relapse occurs more frequently and earlier. Despite these differences, the prognosis after stage-adapted treatment is favourable for both patient groups. Some cases presenting with a variant histology show a histopathological and clinical overlap with T-cell/histiocyte rich large B-cell lymphoma (THRLBCL). Although being considered as aggressive B-cell lymphoma, THRLBCL exhibits many features that are similar to NLPHL, indicating a close relationship with regard to pathogenesis. Both lymphoma entities derive from germinal centre B-cells, show ongoing somatic hypermutation, and resemble each other in terms of gene expression of tumour cells, genomic imbalances and mutation patterns.


Assuntos
Linfócitos B/patologia , Doença de Hodgkin/patologia , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Doença de Hodgkin/diagnóstico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Patologia Clínica/métodos , Linfócitos T/patologia
10.
J Clin Oncol ; 38(7): 698-705, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626571

RESUMO

PURPOSE: The optimal treatment of newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. We therefore conducted a retrospective analysis using the database of the German Hodgkin Study Group (GHSG). PATIENTS AND METHODS: The long-term course of 471 patients with NLPHL (early stages, n = 251; intermediate stages, n = 76; advanced stages, n = 144) who had received stage-adapted first-line treatment in the randomized GHSG HD7 to HD15 studies was investigated. Treatment consisted of radiotherapy alone, chemotherapy alone, or combined-modality approaches. RESULTS: The median age at NLPHL diagnosis was 39 years (range, 16 to 75 years). Patients were mostly male (75.8%). The median observation time was 9.2 years. At 10 years, progression-free survival and overall survival estimates were 75.5% and 92.1% (early stages, 79.7% and 93.3%; intermediate stages, 72.1% and 96.2%; advanced stages, 69.8% and 87.4%), respectively. A total of 48 patients (10.2%) developed a second malignancy during follow-up (non-Hodgkin lymphoma, n = 13; leukemia, n = 6; solid tumor, n = 25; unspecified malignancy, n = 4). Death occurred in 43 patients (9.1%). However, only a minority of deaths were NLPHL related (n = 10), whereas second malignancies (n = 20) and nonmalignant conditions possibly associated with radiotherapy or chemotherapy (n = 13) caused the death in the majority of patients. CONCLUSION: The overall outcome of patients with NLPHL who had received Hodgkin lymphoma-directed first-line treatment in randomized GHSG trial protocols was good. Nonetheless, treatment optimization is still necessary to reduce toxicity in standard-risk patients and to improve the prognosis in high-risk patients.

12.
Am J Hematol ; 94(11): 1208-1213, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31396979

RESUMO

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can present with different histopathological growth patterns. The impact of these histopathological growth patterns on relapse characteristics is unknown. We therefore analyzed paired biopsies obtained at initial diagnosis and relapse from 33 NLPHL patients who had received first-line treatment within German Hodgkin Study Group (GHSG) trial protocols, and from a second cohort of 41 relapsed NLPHL patients who had been treated outside GHSG studies. Among the 33 GHSG patients, 21 patients presented with a typical growth pattern at initial diagnosis, whereas 12 patients had a variant histology. The histopathological growth patterns at initial diagnosis and at relapse were consistent in 67% of cases. A variant histology at initial diagnosis was associated with a shorter median time to lymphoma recurrence (2.8 vs 5.2 years; P = .0219). A similar tendency towards a shorter median time to lymphoma recurrence was observed for patients presenting with a variant histology at relapse, irrespective of the growth pattern at initial diagnosis. Results obtained from the 41 NLPHL patients who had been treated outside GHSG studies were comparable (median time to lymphoma recurrence for variant histology vs typical growth pattern at initial diagnosis: 1.5 vs 7.0 years). In conclusion, the histopathological growth pattern remains consistent at relapse in the majority of NLPHL cases, and has major impact on the time of relapse.


Assuntos
Intervalo Livre de Doença , Doença de Hodgkin/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Terapia Combinada , Feminino , Seguimentos , Alemanha/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Recidiva , Rituximab/uso terapêutico , Transplante Autólogo
13.
J Intensive Care ; 7: 41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410290

RESUMO

Background: With Sepsis-3, the increase in sequential organ failure assessment (SOFA) as a clinical score for the identification of patients with sepsis and quickSOFA (qSOFA) for the identification of patients at risk of sepsis outside the intensive care unit (ICU) were introduced in 2016. However, their validity has been questioned, and their applicability in different settings and subgroups, such as hematological cancer patients, remains unclear. We therefore assessed the validity of SOFA, qSOFA, and the systemic inflammatory response syndrome (SIRS) criteria regarding the diagnosis of sepsis and the prediction of in-hospital mortality in a multicenter cohort of hematological cancer patients treated on ICU and non-ICU settings. Methods: We retrospectively calculated SIRS, SOFA, and qSOFA scores in our cohort and applied the definition of sepsis as "life-threatening organ dysfunction caused by dysregulated host response to infection" as reference. Discriminatory capacity was assessed using the area under the receiver operating characteristic curve (AUROC). Results: Among 450 patients with hematological cancer (median age 58 years, 274 males [61%]), 180 (40%) had sepsis of which 101 (56%) were treated on ICU. For the diagnosis of sepsis, sensitivity was 86%, 64%, and 42% for SIRS, SOFA, and qSOFA, respectively. However, the AUROCs of SOFA and qSOFA indicated better discrimination for sepsis than SIRS (SOFA, 0.69 [95% CI, 0.64-0.73] p < 0.001; qSOFA, 0.67 [95% CI, 0.62-0.71] p < 0.001; SIRS, 0.57 [95% CI, 0.53-0.61] p < 0.001).In-hospital mortality was 40% and 14% in patients with and without sepsis, respectively (p < 0.001). Regarding patients with sepsis, mortality was similar in patients with positive and negative SIRS scores (39% vs. 40% (p = 0.899), respectively). For patients with qSOFA ≥ 2, mortality was 49% compared to 33% for those with qSOFA < 2 (p = 0.056), and for SOFA 56% vs. 11% (p < 0.001), respectively. SOFA allowed significantly better discrimination for in-hospital mortality (AUROC 0.74 [95% CI, 0.69-0.79] p < 0.001) than qSOFA (AUROC 0.65 [95% CI, 0.60-0.71] p < 0.001) or SIRS (AUROC 0.49 [95% CI, 0.44-0.54] p < 0.001). Conclusions: An increase in SOFA score of ≥ 2 had better prognostic accuracy for both diagnosis of sepsis and in-hospital mortality in this setting, and especially on ICU, we observed limited validity of SIRS criteria and qSOFA in identifying hematological patients with sepsis and at high risk of death.

15.
Eur J Haematol ; 103(3): 268-271, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211882

RESUMO

Follicular lymphoma is the most common subtype of the indolent non-Hodgkin lymphomas. Treatment usually consists of immuno-chemotherapy and results in long-lasting remissions in most cases. Progression-free survival with the second-generation anti-CD20 antibody obinutuzumab was shown to be better than with rituximab when given in combination with either bendamustine or anthracycline-based chemotherapy. Although treatment is generally well tolerated without an excessive rate of toxicities, there appear to be slightly more adverse events with obinutuzumab than with rituximab. Here, we report the case of a 45-year-old female patient that was diagnosed with a disseminated enterovirus infection while undergoing maintenance therapy with obinutuzumab after induction treatment with the combination of bendamustine and rituximab. Enterovirus RNA was detected in the blood, the cerebrospinal fluid, and the colon. A therapy with intravenous immunoglobulins was initiated since the patient presented with a severe treatment-related immunosuppression indicated by hypogammaglobulinemia. Nonetheless, she eventually died from the enterovirus infection without evidence of lymphoma progression. This case underscores that clinicians should be aware of rare but potentially fatal infectious complications related to treatment protocols containing anti-CD20 antibodies.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/etiologia , Linfoma Folicular/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Evolução Fatal , Feminino , Humanos , Linfoma Folicular/tratamento farmacológico , Quimioterapia de Manutenção , Pessoa de Meia-Idade
16.
Hemasphere ; 3(5): e296, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31942547
17.
Br J Haematol ; 185(1): 42-52, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30592027

RESUMO

About 30% of all Hodgkin lymphoma (HL) patients are ≥60 years old. As lenalidomide has promising single agent activity in multiple relapsed HL, we replaced bleomycin in ABVD with lenalidomide in this phase-I trial. Patients aged ≥60 years with early-unfavourable- or advanced-stage HL (Eastern Cooperative Oncology Group performance status ≤2, Cumulative Illness Rating Scale for Geriatrics score 0-7) received 4-8 cycles of AVD (doxorubicin, vinblastine, dacarbazine) and lenalidomide in escalation with overdose control. Dose-limiting toxicities (DLTs) included thromboembolism ≥grade 2, severe haematological toxicity, neutropenic fever and prolonged therapy delay. Twenty-five patients with a median age of 68 years were included, 68% had advanced-stage HL. A pre-defined stopping criterion for dose escalation after DLT evaluation of 20/24 patients suggested a recommended phase II dose (RPTD) of 20 mg. DLTs occurred in 10/24 evaluable patients, all treated with ≥20 mg, however, median relative dose intensity was 97% (interquartile range 49-104%). Grade 3 or higher toxicities occurred in all 22 patients at ≥20 mg lenalidomide but no treatment-related deaths occurred. Overall response rate was 80% for all patients (20/25) and 86% (19/22) at ≥20 mg lenalidomide. Three-year estimates for progression-free survival and OS were 69·7% (95% CI: 50·3-89·1%) and 83·8% (95%-CI: 69·3-98·4%), respectively. In conclusion, AVD with lenalidomide 20 mg is feasible and highly effective in older HL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Humanos , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento , Vimblastina/administração & dosagem
18.
Blood ; 132(14): 1519-1525, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30064977

RESUMO

The optimal treatment of patients with relapsed or refractory nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. To shed more light on treatment options and outcome, we performed an analysis using the database of the German Hodgkin Study Group (GHSG). Ninety-nine patients who had received first-line treatment within 12 prospective GHSG studies conducted between 1993 and 2009, and subsequently developed disease recurrence (n = 91) or had primary disease progression (n = 8), were included. At initial NLPHL diagnosis, the median age was 40 years and 76% of patients were male. First-line treatment consisted of radiotherapy (RT) alone (20%), chemotherapy with or without RT (74%), and the anti-CD20 antibody (Ab) rituximab (6%), respectively. The median follow-up from initial diagnosis was 11.2 years. The median time to disease recurrence was 3.7 years. The applied salvage approaches included single-agent anti-CD20 Ab treatment or RT alone (37%), conventional chemotherapy (CT) with or without anti-CD20 Ab treatment with or without RT (27%) and high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) (31%). No salvage treatment was given in 4% of patients. The 5-year progression-free survival and overall survival estimates after NLPHL recurrence were 75.6% and 89.5% (74.1% and 97.2% after single-agent anti-CD20 Ab treatment or RT alone; 68.0% and 77.8% after CT with or without anti-CD20 Ab treatment with or without RT; 84.6% and 89.8% after HDCT and ASCT). Hence, patients with relapsed or refractory NLPHL had a good overall prognosis. Factors such as time to disease recurrence and previous treatment may guide the choice of the optimal salvage approach for the individual patient.


Assuntos
Doença de Hodgkin/terapia , Linfócitos/patologia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Terapia Combinada , Feminino , Seguimentos , Alemanha/epidemiologia , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Rituximab/uso terapêutico , Terapia de Salvação , Transplante de Células-Tronco , Análise de Sobrevida , Adulto Jovem
19.
Dtsch Arztebl Int ; 115(31-32): 535-540, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30149835

RESUMO

BACKGROUND: Hodgkin lymphoma is the most common neoplasm in young adults, with an incidence of 2 to 3 cases per 100 000 persons per year. Risk-adapted chemotherapy and radiotherapy usually lead to cure. Finding ways to lessen the treatment- associated morbidity and mortality is a major goal of current research. METHODS: For the creation of an updated guideline (DKH grant number 111778), a systematic literature search was carried out in medical databases (MEDLINE, CENTRAL) and guideline databases (GIN) (search dates: January 2012 to June 2017). RESULTS: Results from 10 meta-analyses, 89 randomized and controlled trials, and 81 prospective or retrospective trials were evaluated. The use of positron emission tomography (PET) is strongly recommended in the initial diagnostic evaluation, as well as for the guidance of treatment in advanced stages. In early stages, two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and involved-site radiotherapy (IS-RT) at a dose of 20 Gy are recommended. For the treatment of intermedi- ate stages, two cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) + two cycles of ABVD and 30 Gy IS-RT are recommended. In advanced stages, two cycles of escalated BEACOPP are administered, and then PET is performed for the guidance of further treatment: two further cycles of escalated BEACOPP are recommended if the PET is negative and four further cycles if it is positive, followed by radiotherapy of PET- positive residual tumor tissue. The five-year survival of patients with Hodgkin lymphoma is 95%. In case of disease recurrence, high-dose chemotherapy followed by autologous stem-cell transplantation is performed, and targeted drugs including brentuxi- mab vedotin, nivolumab, and pembrolizuab are used. CONCLUSION: The highly favorable long-term prognosis of HL necessitates careful consideration of the intensity of treatment as well as thorough follow-up to enable the detection of late sequelae, such as second tumors or organ damage.


Assuntos
Doença de Hodgkin/classificação , Doença de Hodgkin/terapia , Adulto , Tratamento Farmacológico/métodos , Guias como Assunto , Doença de Hodgkin/fisiopatologia , Humanos , Estadiamento de Neoplasias/métodos , Prognóstico , Radioterapia/métodos
20.
J Clin Oncol ; 36(25): 2603-2611, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29989855

RESUMO

Purpose The prognostic effect of isolated infradiaphragmatic involvement in Hodgkin lymphoma (HL) is controversial, and there are little data about patients treated with current therapies. Therefore, we performed a risk factor analysis to focus on isolated nodal infradiaphragmatic disease in patients treated within the German Hodgkin Study Group trials HD13 (clinical trial information: ISRCTN63474366) and HD14 (clinical trial information: ISRCTN04761296) for early-stage HL. Patients and Methods Characteristics and outcomes of patients who had infradiaphragmatic HL were compared with patients who had supradiaphragmatic disease. Progression-free survival (PFS) and overall survival (OS) were estimated according to Kaplan-Meier methods and were compared between groups using the log-rank test and Cox proportional hazards regression, which was also applied for multivariable analyses that adjusted for relevant baseline characteristics. Results Of 2,903 qualified patients, 223 (7.7%) were diagnosed with isolated nodal infradiaphragmatic disease. In general, these patients were older, had a poorer performance status, were more often male, and had the nodular sclerosis subtype less often than those with supradiaphragmatic disease. After a median follow-up time of 51 months, PFS and OS were significantly worse in patients with infradiaphragmatic disease (5-year PFS and OS, 80.1% and 91.5% v 91.2% and 97.6% in patients with supradiaphragmatic disease; each P < .001). In multivariable analyses, infradiaphragmatic HL remained a significant risk factor in terms of PFS (hazard ratio [HR], 1.5; 95% CI, 1.04 to 2.2; P = .03) and OS (HR, 2.0; 95% CI, 1.2 to 3.5; P = .01). However, inferior PFS and OS could not be observed among those patients treated with the more intensive chemotherapy (two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] in HD13, and two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPPescalated] plus two cycles of ABVD in HD14; all patients received 30 Gy of involved-field radiotherapy). Conclusion Early-stage HL that presents with infradiaphragmatic disease only represents a distinct patient group with an inferior outcome. However, this adverse outcome can be outweighed by appropriate combined modality treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Metástase Linfática/patologia , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença de Hodgkin/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Intervalo Livre de Progressão , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
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