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1.
Lancet Haematol ; 8(3): e171, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33636140
2.
Ann Hematol ; 100(4): 1049-1058, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33641019

RESUMO

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial ("real-world") patients, aged 16-59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18-59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ensaios Clínicos como Assunto/estatística & dados numéricos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Inglaterra/epidemiologia , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Prednisona/administração & dosagem , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/epidemiologia , Procarbazina/administração & dosagem , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
3.
Rinsho Ketsueki ; 62(1): 14-19, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33551419

RESUMO

Although classic Hodgkin's lymphoma (CHL) sometimes develops after treatment for multiple myeloma (MM), simultaneous diagnosis of both malignancies is extremely rare without previous treatment history. Here we describe a case of a 54-year-old female who complained of left cervical lymphadenopathy. Biopsy specimen from the left cervical lymph node revealed mixed-cellularity CHL. Bone marrow aspirate comprised 10.3% plasma cells. She was diagnosed with MM due to involved: uninvolved serum free light chain ratio of >100. She achieved complete response for CHL after 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy along with 30 Gy of involved-field radiotherapy. Three years later, bortezomib, lenalidomide, and dexamethasone (VRd-lite) therapy was initiated for MM. Severe neutropenia during her 1st cycle prompted a dosage reduction of lenalidomide and bortezomib. Partial response was achieved after 4 cycles of VRd-lite followed by high-dose melphalan/autologous stem cell transplantation. No severe adverse events were recorded. This was followed by 4 cycles of carfilzomib, lenalidomide, and dexamethasone therapy, which resulted in complete remission. As the number of elderly people increases, multiple myeloma patients with previous history of other malignancies would increase. Our case has shown that VRd-lite therapy may be suitable for those patients.


Assuntos
Doença de Hodgkin , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Transplante Autólogo
4.
BMJ Case Rep ; 14(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563686

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) can cause a wide range of skin infections, however MRSA panniculitis without bacteremia is a rare manifestation. Here, we report a woman in her 20s with relapsed Hodgkin lymphoma undergoing stem cell mobilisation who presented with bilateral subcutaneous nodules over her shins. Ultrasound scan of one nodule showed non-specific inflammatory changes. Punch biopsy of a nodule showed lobular panniculitis with Gram-positive cocci. Blood cultures were negative but a culture from the biopsy grew MRSA. She was started on doxycycline with improvement in her symptoms. This case serves as a reminder to consider infections as a cause of panniculitis in immunocompromised patients.


Assuntos
Mobilização de Células-Tronco Hematopoéticas , Paniculite/microbiologia , Infecções Estafilocócicas/microbiologia , Adulto , Antibacterianos/uso terapêutico , Biópsia , Doxiciclina/uso terapêutico , Feminino , Doença de Hodgkin/terapia , Humanos , Hospedeiro Imunocomprometido , Staphylococcus aureus Resistente à Meticilina , Paniculite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico
5.
BMJ Case Rep ; 14(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408107

RESUMO

A 38-year-old male patient presented to the ear, nose and throat department with shortness of breath over last 2 months. The CT scan of the neck and chest revealed a 3.3×3 cm tumour behind the right thyroid lobe extending into the tracheo-oesophageal (TO) groove with tracheal compression. The ultrasound scan of the neck and targeted fine needle aspiration followed by core biopsy raised a suspicion of Hodgkin's lymphoma. The patient underwent a right hemithyroidectomy and incisional biopsy of the right TO groove tumour. The histology confirmed a Hasenclever's three nodular sclerosing Hodgkin's lymphoma for which he received adjuvant chemotherapy. An incidental pT1a pN0 thyroid papillary microcarcinoma in the adjacent thyroid parenchyma was completely excised. This represents a case of TO Hodgkin's lymphoma, of which there are no current published case reports. We aim to raise awareness about this rare condition by sharing the diagnostic work up and successful management in a multidisciplinary team setting.


Assuntos
Carcinoma Papilar/diagnóstico , Neoplasias Esofágicas/diagnóstico , Doença de Hodgkin/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Sons Respiratórios , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Traqueia/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia com Agulha de Grande Calibre , Carcinoma Papilar/complicações , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Quimioterapia Adjuvante , Diagnóstico Diferencial , Dispneia/etiologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Esôfago/diagnóstico por imagem , Esôfago/patologia , Esôfago/cirurgia , Doença de Hodgkin/complicações , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Achados Incidentais , Masculino , Esvaziamento Cervical , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/complicações , Neoplasias da Traqueia/patologia , Neoplasias da Traqueia/cirurgia , Resultado do Tratamento , Ultrassonografia
6.
BMJ Case Rep ; 14(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408110

RESUMO

A 10-year-old boy underwent stem cell transplant for Hodgkin's lymphoma and developed vomiting and seizure in the postoperative period. An ophthalmic referral was made from intensive care unit, to rule out papilledema. On examination, there was no papilledema in both eyes, instead there were areas of retinal necrosis with no haemorrhages or vitritis in right eye. Cerebrospinal fluid serology was negative for herpes but MRI showed hyperintensity in temporal lobe. A clinical diagnosis of progressive outer retinal necrosis (PORN) was made and fundus picture was documented with help of a smartphone and 20D lens. High-dose intravenous injection acyclovir was started and PORN lesion improved on treatment.


Assuntos
Antivirais/administração & dosagem , Transplante de Medula Óssea/efeitos adversos , Infecções por Herpesviridae/diagnóstico , Doença de Hodgkin/terapia , Retina/patologia , Retinite/diagnóstico , Aciclovir/administração & dosagem , Criança , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/imunologia , Doença de Hodgkin/imunologia , Humanos , Imunossupressores/efeitos adversos , Achados Incidentais , Imagem por Ressonância Magnética , Masculino , Necrose/diagnóstico , Necrose/tratamento farmacológico , Necrose/imunologia , Retina/diagnóstico por imagem , Retina/virologia , Síndrome de Necrose Retiniana Aguda/diagnóstico , Retinite/tratamento farmacológico , Retinite/imunologia , Resultado do Tratamento , Ativação Viral/imunologia
7.
Lancet Haematol ; 8(1): e67-e79, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33357485

RESUMO

PET using 18F-fluorodeoxyglucose is central to the management of patients with Hodgkin lymphoma, and PET-adapted strategies have facilitated major improvements in overall survival. Although unmet needs include addressing fertility preservation, cardiovascular health, and survivorship issues, along with a need for better cure rates in the older patient, the improved survival of most patients with Hodgkin lymphoma globally is a triumph of the complementary approaches and collaboration of many cooperative groups in the study of PET-guided therapy. The optimal strategy for this highly curable lymphoma, however, remains a topic of intense discussion and polarises opinion among clinicians. In this Review, we seek not to debate the many controversies that exist but to better inform the treating haematologist to assist in navigating a patient-specific approach. Focusing primarily on phase 3 studies, we chart the changes in management based on the most relevant technological advance in the past decade, the standardisation of PET-CT for staging, interim, and end-of-treatment response assessment of Hodgkin lymphoma.


Assuntos
Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/normas , Intervalo Livre de Doença , Humanos , Estadiamento de Neoplasias/normas , Taxa de Sobrevida
8.
Crit Rev Oncol Hematol ; 157: 103175, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33321295

RESUMO

Second breast cancer (SBC) is the most common solid cancer among Hodgkin Lymphoma (HL) female survivors. We reviewed the related modifying risk factors, radiation-induced carcinogenesis, tumors characteristics, management specificities, prevention and surveillance modalities based on current evidence. The risk of developing SBC may be influenced essentially by the age at HL treatment, follow-up latency, dose of irradiation received and the extent of irradiated field. SBCs generally develop at younger age, they are often bilateral, and exhibit more aggressive biological features and worse prognosis. No firm answer about the benefits of breast surveillance is provided by literature, but compelling evidence tends toward a clinical benefit in early detection. Increasing awareness among health providers' care and current survivors as well as the implementation of screening measures is crucial. Great efforts are ongoing in individualizing treatment strategies for future HL patients and response-adapted approaches are holding promise in prevention of these second malignancies.


Assuntos
Neoplasias da Mama , Doença de Hodgkin , Segunda Neoplasia Primária , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/terapia , Humanos , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Sobreviventes
9.
PLoS One ; 15(12): e0242218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370316

RESUMO

Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual's burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aberrações Cromossômicas/efeitos dos fármacos , Doença de Hodgkin/terapia , Meiose/efeitos dos fármacos , Análise do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Adulto , Células-Tronco Germinativas Adultas/efeitos dos fármacos , Células-Tronco Germinativas Adultas/efeitos da radiação , Sobreviventes de Câncer , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Aberrações Cromossômicas/efeitos da radiação , Estudos de Coortes , Preservação da Fertilidade , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Meiose/efeitos da radiação , Mitoxantrona/efeitos adversos , Mutagênese/efeitos dos fármacos , Mutagênese/efeitos da radiação , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Prednisona/efeitos adversos , Dosagem Radioterapêutica , Espermatogênese/efeitos dos fármacos , Espermatogênese/efeitos da radiação , Espermatozoides/fisiologia , Espermatozoides/efeitos da radiação , Testículo/efeitos dos fármacos , Testículo/efeitos da radiação , Fatores de Tempo , Vimblastina/efeitos adversos , Vincristina/efeitos adversos
10.
Ann Hematol ; 99(10): 2385-2392, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748163

RESUMO

Up to 30% of patients with classical Hodgkin lymphoma (cHL) are not responsive to frontline therapy or relapse after primary treatment. In these cases, autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care. The combination of brentuximab vedotin and bendamustine (BV + B) is an effective salvage regimen in this challenging subpopulation. This nationwide multicenter study investigated the real-world efficacy and safety of the BV + B regimen as a bridge to AHSCT in patients with primary refractory or relapsed cHL. A total of 41 cHL patients underwent AHSCT after receiving at least 1 cycle of BV + B (with brentuximab vedotin given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1-2 every 4 weeks). After a median of 3 (1-6) cycles of BV + B, the objective response rate was 78%, with 29 (70.7%) patients achieving complete remission. Twelve (29.3%) patients relapsed after AHSCT, 2 (4.9%) of them died, while 2 (4.9%) patients are lost to follow-up. After a median of 17 months of follow-up, the estimated 2-year overall- and progression-free survival after AHSCT was 93 and 62%, respectively. Features of advanced disease at recurrence (p = 0.038) and the presence of stage IV cHL at relapse (p = 0.024) are strong predictor markers of unfavorable outcomes. Twenty-four (58.5%) patients experienced adverse events of any grade, while no grade IV toxicities were reported. BV + B is an effective salvage option with a manageable toxicity profile in cHL. The real-world safety and efficacy of this combination are similar to the observations made on the study population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Brentuximab Vedotin/administração & dosagem , Brentuximab Vedotin/efeitos adversos , Terapia Combinada , Avaliação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Neutropenia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
11.
Int J Hematol ; 112(5): 674-689, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32748216

RESUMO

We conducted a multicenter study on anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) before/after allogeneic hematopoietic cell transplantation (allo-HCT) for Hodgkin lymphoma. Anti-PD-1 mAbs were administered to 25 patients before allo-HCT and to 20 after allo-HCT. In pre-allo-HCT setting, the median interval from the last administration to allo-HCT was 59 days. After allo-HCT, 12 patients developed non-infectious febrile syndrome requiring high-dose corticosteroid. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGvHD) were 47.1%. Eight patients who had GvHD prophylaxis with post-transplant cyclophosphamide (PTCy) had less frequent aGvHD (grade II-IV, 14.6% versus 58.8%; P = 0.086). The 1 year overall survival (OS), relapse/progression, and non-relapse mortality rates were 81.3%, 27.9%, and 8.4%. In post-allo-HCT setting, the median interval from allo-HCT to the first administration was 589 days. The overall and complete response rates were 75% and 40%. At 100 days after anti-PD-1 therapy, the cumulative incidences of grade II-IV aGvHD, moderate-to-severe chronic GvHD, and grade 3-4 immune-related toxicity were 15.0%, 30.0%, and 30.0%. While the 1 year relapse/progression rate was 47.4%, the 1 year OS probability was 89.7%. In conclusion, immune-related complications were frequent despite modifications of GvHD prophylaxis or anti-PD-1 mAb dosing. In anti-PD-1-mAb-pretreated patients, PTCy-based GvHD prophylaxis may be effective.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Receptor de Morte Celular Programada 1/imunologia , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Ciclofosfamida/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/mortalidade , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Segurança , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
12.
Ann Hematol ; 99(11): 2565-2576, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32507911

RESUMO

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Nivolumabe/administração & dosagem , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Transplante de Células-Tronco , Taxa de Sobrevida
13.
Cancer Treat Rev ; 88: 102042, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32521386

RESUMO

Since the clinical introduction of anti-CD20 monoclonal antibodies into lymphoma treatment, immunologic approaches in lymphoma have made substantial progress. Advances in our understanding of tumor immunology have led to the development of strategies to overcome immunologic barriers responsible for an ineffective immune response. Specifically, therapeutic agents have been developed and tested against molecules that are responsible for T-cell exhaustion. The use of monoclonal antibodies against immune checkpoints in the adaptive immune system, such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, has changed the landscape of cancer therapy including the treatment of lymphoma. This achievement has recently been accompanied by the development of novel immune checkpoint inhibitors targeting the innate immune system, including the CD47-SIRPα signaling pathway, and this approach has yielded promising results. To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells.


Assuntos
Doença de Hodgkin/imunologia , Doença de Hodgkin/terapia , Imunoterapia/métodos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/terapia , Imunidade Adaptativa , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Imunidade Inata , Ensaios Clínicos Controlados Aleatórios como Assunto , Linfócitos T/imunologia
14.
Pediatr Blood Cancer ; 67(8): e28365, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32491274

RESUMO

Hepatic involvement in Hodgkin lymphoma (HL) is uncommon (∼5% of patients) but always implies stage IV disease. Accurate staging is mandatory for making the appropriate risk assignment and treatment decisions. The Staging Evaluation and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) international working group conducted a systematic literature review of liver involvement in HL patients with the aim to propose a universally acceptable definition for liver involvement in pediatric HL. Thirty-three articles describing 6985 pediatric and adult HL patients were reviewed, of which 539 (7.7%) mentioned liver involvement. The literature did not provide a uniform definition of hepatic involvement and we propose consensus criteria derived from the EuroNet and Children's Oncology Group protocols, where liver involvement is defined as any hepatic lesion on computed tomography scan that correlates with 18 F-FDG uptake greater than background liver. A clear definition of liver lesions is necessary to consistently identify liver involvement and compare its impact on outcomes among protocols worldwide.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Lactente , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Estadiamento de Neoplasias , Adulto Jovem
15.
Ann Hematol ; 99(7): 1575-1581, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32500223

RESUMO

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Estudos de Casos e Controles , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Etoposídeo/uso terapêutico , Feminino , Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/sangue , Doença de Hodgkin/complicações , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/complicações , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
17.
Am J Hematol ; 95(8): 978-989, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32384177

RESUMO

DISEASE OVERVIEW: Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8480 new patients annually and representing approximately 10% of all lymphomas in the United States. DIAGNOSIS: Hodgkin lymphoma is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. RISK STRATIFICATION: An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. RISK-ADAPTED THERAPY: Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy, followed by involved-field radiation therapy. Patients with advanced stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents including brentuximab vedotin and anti-PD-1 antibodies are now being incorporated into frontline therapy. MANAGEMENT OF RELAPSED/REFRACTORY DISEASE: High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant or participation in a clinical trial should be considered.


Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Feminino , História do Século XXI , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
J Cancer Res Ther ; 16(1): 1-6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362601

RESUMO

Background: Hodgkin's lymphoma (HL) can be treated with combined modality treatment (CMT) to limit long-term toxicities in the early favorable stage. Early unfavorable and advanced stage HL is mainly treated with chemotherapy followed by radiation to the bulky site. This study examines the impact of CMT in early as well as advanced stage HL. Materials and Methods: From 2001 to 2011, 125 patients with Stage I to IV HL were analyzed. Median age of the patients was 25 years (range 12-68 years). CMT, chemotherapy, and radiation alone were given to 51, 64, and 10 patients, respectively. Chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was given to 100 patients, 6 patients received ABVD-like regimen, and 9 patients received cyclophosphamide, vincristine, procarbazine, and prednisone regimen. Radiotherapy (RT) was given to 61 (49%) patients, involved field RT to 55 (90%), and extended-field RT to 6 (10%) patients, respectively. Median radiation dose was 30 Gy (18-40 Gy). Results: All 25 patients with early-stage achieved complete response (CR) with CMT. At a median follow-up of 70 months (range 12-230 months), relapse was seen in two patients (1 local and 1 distant). Of 26 patients with advanced stage, 25 achieved a CR and 1 had stable disease with CMT. Relapse occurred in one patient (distant). In patients with early-stage treated with chemotherapy only ( n = 30, 24%), 9 patients had relapse (4 local and 5 distant) while in those with RT only ( n = 10, 8%), 4 developed distant relapse. In patients with advanced stage treated with chemotherapy only ( n = 34, 27%), 8 relapsed (5 local and distant, 3 distant only). Patients with relapse were salvaged with CMT ( n = 6), chemotherapy ( n = 15), or RT ( n = 3). Two patients have died. Five years' disease-free survival (DFS) in patients with early favorable stage, early unfavorable stage, and advanced stage was 91%, 82%, and 73%, respectively ( P = 0.026). DFS was significantly better with CMT than chemotherapy or radiation alone. Five years' overall survival (OS) was 93%, 92%, and 84%, respectively ( P = 0.139). Second malignancy occurred in 3 (2.4%) patients; carcinoma of the tongue, pseudomyxoma peritonei, and non-HL each, respectively. None of these patients had received prior radiation. Conclusion: CMT improved DFS in patients with HL. OS was similar in all patients irrespective of treatment combinations. The incidence of second malignancy was 2.4%.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Radioterapia/mortalidade , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Criança , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
19.
Cancer Radiother ; 24(4): 335-339, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32444284

RESUMO

Hodgkin lymphoma (HL) is a disease characterized by a high curability rate, and the treatment benefit-risk balance must be carefully addressed to achieve complete disease control with low risk of long-term toxicities. Most patients are treated with a combination of chemotherapy and radiotherapy, after disease staging and response to treatment evaluated by FDG PET/CT. We report the case of a 28-year-old patient concomitantly diagnosed of a Hodgkin lymphoma and active tuberculosis. Initial staging was difficult due to pulmonary and abdominal tuberculosis localization that induced FDG PET/CT hypermetabolism. Anti-tuberculosis treatment was first started, allowing secondary an early accurate Hodgkin lymphoma staging by FDG PET/CT. The patient was then treated by chemotherapy and radiotherapy. Helical TomoTherapy® was used with involved site (IS) irradiation volume was performed to decrease the high doses to organs-at-risk (OAR), especially lungs in this context of tuberculosis.


Assuntos
Doenças do Colo/tratamento farmacológico , Doença de Hodgkin/terapia , Tuberculose Gastrointestinal/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antituberculosos/uso terapêutico , Bleomicina/administração & dosagem , Doenças do Colo/complicações , Doenças do Colo/diagnóstico por imagem , Doenças do Colo/metabolismo , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Doença de Hodgkin/complicações , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Humanos , Pulmão , Linfonodos/diagnóstico por imagem , Linfonodos/metabolismo , Masculino , Órgãos em Risco , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radioterapia de Intensidade Modulada , Medição de Risco , Tomografia Computadorizada por Raios X , Tuberculose Gastrointestinal/complicações , Tuberculose Gastrointestinal/diagnóstico por imagem , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagem , Vimblastina/administração & dosagem
20.
Pediatr Blood Cancer ; 67(7): e28322, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32391955

RESUMO

BACKGROUND: The WHO Global Initiative for Childhood Cancer aims to increase survival to at least 60% for all children with cancer globally, with initial focus on six common curable cancer types. Frequent causes of treatment failure in low income countries (LICs) are treatment abandonment and death during treatment. Here, we report on the outcome at the end of treatment of patients with newly diagnosed common and curable cancer types, admitted in the Queen Elizabeth Central Hospital, Blantyre, Malawi. PROCEDURE: Outcome at end of treatment was documented and analyzed retrospectively for all children with a working diagnosis of a common and curable cancer type (ALL, Hodgkin disease, Wilms tumor, retinoblastoma, and Burkitt lymphoma) admitted over a 2-year period. Patients with a misdiagnosis were excluded. Outcomes were categorized as alive without evidence of disease, treatment abandonment, death during treatment, or persistent disease. RESULTS: We included 264 patients. Seven patients with a misdiagnosis were excluded. At the end of treatment, 53% (139 of 264) of patients were alive without evidence of disease, 19% (49 of 264) had abandoned treatment, 23% (61 of 264) had died during treatment, and 6% (15 of 264) had persistent disease. CONCLUSION: Survival of children with common and curable cancers is (significantly) below 50%. Almost half (42%) of the patients either abandoned treatment or died during treatment. Strategies to enable parents to complete treatment of their child and improved supportive care are needed. Such interventions may need to be given priority to improve the currently poor survival.


Assuntos
Linfoma de Burkitt/mortalidade , Doença de Hodgkin/mortalidade , Neoplasias/mortalidade , Retinoblastoma/mortalidade , Tumor de Wilms/mortalidade , Adolescente , Linfoma de Burkitt/patologia , Linfoma de Burkitt/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Lactente , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Malaui , Masculino , Neoplasias/patologia , Neoplasias/terapia , Prognóstico , Neoplasias da Retina/mortalidade , Neoplasias da Retina/patologia , Neoplasias da Retina/terapia , Retinoblastoma/patologia , Retinoblastoma/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Tumor de Wilms/patologia , Tumor de Wilms/terapia
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