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1.
Lancet Haematol ; 7(9): e660-e670, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32853585

RESUMO

BACKGROUND: Recognising that the immune suppressive microenvironment promotes tumour growth in Hodgkin lymphoma, we hypothesised that activating immunity might augment the activity of targeted chemotherapy. We evaluated the safety and activity of combinations of brentuximab vedotin with nivolumab or ipilimumab, or both in patients with relapsed or refractory Hodgkin lymphoma. METHODS: In this multicentre, open-label, phase 1/2 trial, patients with relapsed or refractory Hodgkin lymphoma aged 18 years or older who had relapsed after at least one line of therapy, with an Eastern Cooperative Oncology Group performance status of 2 or lower, and adequate organ and marrow function, with no pulmonary dysfunction were eligible for inclusion. Phase 1 primary objectives were to determine the maximum tolerated dose and dose limiting toxicities of brentuximab vedotin combined with ipilimumab (ipilimumab group), nivolumab (nivolumab group), or both (triplet therapy group) using a 3 + 3 dose escalation design with expansion cohorts. During the dose escalation phase, patients were enrolled sequentially into one of six cohorts: in the ipilimumab group fixed brentuximab vedotin 1·8 mg/kg with ipilimumab 1 mg/kg (cohort A) or 3 mg/kg (cohort B); in the nivolumab group fixed nivolumab 3 mg/kg with brentuximab vedotin 1·2 mg/kg (cohort D) or 1·8 mg/kg (cohort E); and in the triplet therapy group fixed nivolumab 3 mg/kg and ipilimumab 1 mg/kg with brentuximab vedotin 1·2 mg/kg (cohort G) or 1·8 mg/kg (cohort H). Additional patients were enrolled in the expansion phase at the same doses of cohorts B, E, and H. All drugs were given intravenously; brentuximab vedotin and nivolumab were given every 3 weeks, ipilimumab was given every 6 weeks in the ipilimumab group and every 12 weeks in the triplet therapy group. All eligible and treated patients were included in the analysis. This phase 1/2 study is registered with ClinicalTrials.gov, NCT01896999. The phase 2, randomised portion of the trial is still enrolling. FINDINGS: Between March 7, 2014, and Dec 28, 2017, 64 patients were enrolled; two patients in the ipilimumab group and one patient in the nivolumab group were excluded due to ineligibility after enrolment and 61 were evaluable. A total of six dose limiting toxicities were reported in four patients, and the doses used in cohorts B, E, and H were established as maximum tolerated doses and patients were subsequently enrolled onto expansion cohorts (C, F, and I) with these schedules. There were ten (43%) grade 3-4 treatment related adverse events in the ipilimumab group, three (16%) in the nivolumab group, and 11 (50%) in the triplet therapy group including: eight (13%) of 64 patients reporting rash, and colitis, gastritis, pancreatitis and arthritis, and diabetic ketoacidosis each occurring in one (2%) patient. There were two (3%) treatment related deaths, one in the nivolumab group and one in the triplet therapy group. The overall response rate was 76% (95% CI 53-92) in the ipilimumab group, 89% (65-99) in the nivolumab group, and 82% (60-95) in the triplet therapy group, and the complete response rate was 57% (95% CI 34-78%) in the ipilimumab group, 61% (36-83%) in the nivolumab group, and 73% (50-89%) in the triplet therapy group. With a median follow-up of 2·6 years (IQR 1·8-2·9) in the ipilimumab group, 2·4 years (2·2-2·6) in the nivolumab group, and 1·7 years (1·6-1·9) in the triplet therapy group, median progression-free survival is 1·2 years (95% CI 1·7-not reached) in the ipilimumab group, but was not reached in the other two treatment groups. Median overall survival has not been reached in any of the groups. INTERPRETATION: There are clear differences in activity and toxicity of the three combination regimens. The tolerability and preliminary activity for the two most active regimens, brentuximab vedotin with nivolumab and the triplet therapy, are being compared in a randomised phase 2 trial (NCT01896999). FUNDING: Eastern Cooperative Oncology Group-American College of Radiology Imaging Network and the National Cancer Institute of the National Institutes of Health.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Ipilimumab/uso terapêutico , Nivolumabe/uso terapêutico , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Brentuximab Vedotin/efeitos adversos , Progressão da Doença , Quimioterapia Combinada , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Hipersensibilidade/etiologia , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Dor/etiologia , Intervalo Livre de Progressão , Recidiva , Taxa de Sobrevida , Resultado do Tratamento
2.
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
3.
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
4.
Radiology ; 295(3): 651-661, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32286191

RESUMO

Background CT and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT performances following immune therapy are not well known in patients with relapsed or refractory Hodgkin lymphoma (RRHL). Purpose To compare CT and PET/CT for prognostic value of early response evaluation following nivolumab therapy. Materials and Methods This retrospective study included patients from 34 institutions who underwent early imaging response evaluation from July 2013 to April 2017. Three experienced readers classified imaging response by using Cheson et al and 2016 Lymphoma Response to Immunomodulatory Therapy Criteria as follows: complete (metabolic) response, partial (metabolic) response, stable disease or no metabolic response, or progressive (metabolic) disease. Primary CT and PET assessments were performed at a median of 2.0 months (interquartile range, 1.7-3.7 months) after nivolumab initiation. Kaplan-Meier analysis was used to determine the relationship of primary CT and PET assessment response categories to overall survival (OS). Agreements between primary and secondary imaging assessments were assessed by using κ analysis. Results A total of 45 patients (median age, 37 years; range, 18-77 years; 25 men) underwent a primary assessment using CT and PET/CT; 36 patients also underwent a subsequent assessment. Eleven patients (24%) died after a median follow-up of 21.2 months. CT and PET response categories were associated with OS (P = .03 for primary CT assessment; P = .02 for primary PET assessment). There was no pseudoprogression at primary CT and PET assessments. At the primary assessment, response categories by using CT were reclassified by using PET in 44% (20 of 45) of patients. Among these, 55% (11 of 20) were reclassified to complete metabolic response (complete metabolic response rate: 29% [13 of 45 patients] vs complete response rate: 4% [two of 45 patients]), with a 2-year OS probability of 100%. At the secondary assessment, complete response rate using CT increased to 17% (six of 36 patients), hence a better agreement with PET (κ = 0.78; P < .001). Conclusion Early CT and PET/CT at a median of 2 months after initiation of nivolumab predicted overall survival in relapsed or refractory Hodgkin lymphoma. Early PET detected additional patients with complete metabolic response. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Scott and Wang in this issue.


Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Feminino , Doença de Hodgkin/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
5.
Pediatr Blood Cancer ; 67(5): e28230, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134194

RESUMO

AIMS: Classic Hodgkin lymphoma (cHL) is a common malignancy of the pediatric age. Although clinical-radiological features are routinely used for disease risk stratification, the role of tumor histology has yet to be defined. This study aimed to characterize the clinical-pathological features of a large cohort of pediatric cHL specifically investigating the relevance of tumor histology for the prognostic stratification of patients. METHODS AND RESULTS: The study considered 96 clinically annotated cases of pediatric cHL treated according to the AIEOP-LH2004 protocol. The following histological parameters were considered: (i) cHL variant; (ii) grade of nodular sclerosis (NS); (iii) staining for Bcl2 and p53, and expression of B-cell (BCA) and T-cell antigens (TCA) by Hodgkin/Reed-Sternberg cells. The study population consisted of 51 males and 45 females (median age: 13.6 years) with five-year overall and progression-free survival of 94% and 81%, respectively. Most cases featured NS morphology (96%) with a prevalence of NS1 over NS2 grades. Two NS2 variants were recognized (sarcomatous/syncytial and fibrohistiocytic). A consistent subset of cases disclosed positivity for BCA (34%), TCA (26%), p53 (13%), and Bcl2 (19%). Clinical-pathological correlations showed a more aggressive clinical course for NS2 over NS1 cases. The NS2 fibrohistiocytic variant was associated with the worst outcome. No other histological features correlated with prognosis. CONCLUSIONS: Pediatric cHL is a clinically and histologically heterogeneous neoplasm. The majority of cases disclose NS morphology and aberrant phenotypes are frequently encountered. In the pediatric population, NS grading and NS2 subtyping bear significant prognostic impact.


Assuntos
Doença de Hodgkin , Proteínas de Neoplasias/metabolismo , Células de Reed-Sternberg , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/metabolismo , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Células de Reed-Sternberg/metabolismo , Células de Reed-Sternberg/patologia , Estudos Retrospectivos , Taxa de Sobrevida
6.
Cancer Radiother ; 24(3): 206-214, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32171674

RESUMO

PURPOSE: The aim of this study was to extensively describe the epidemiological, clinical and therapeutic outcomes of adolescents and young adults (AYA) population with classical Hodgkin Lymphoma (cHL). Then, a comparison between AYAs and adults and between the subgroups of AYAs treated with the same adult protocol was accomplished to further inform on optimal therapy approach of choice for adolescent patients. MATERIAL AND METHODS: In this mono-centric, retrospective study, we reviewed the medical records. We analyzed 112 consecutive North Tunisian patients, including 66 AYAs (15 to 39 years) and 46 adults (≥40years) affected by cHL treated from 2000 to 2015 at Salah Azaiez Institute. Then, we performed a comparative analysis between AYA and 46 adult patients and a subgroup analysis between adolescents and young adults. All patients were treated according to the national protocol for HL, edited by the Tunisian Society of Hematology. The treatment included chemotherapy and involved-field radiotherapy (RT) at a dose of 20 or 30 Grays (Gy) for responders and 36Gy for non-responders. RESULTS: AYA patients presented with adverse features with nodular sclerosis subtype (p=3.88×10-02) and mediastinal mass involvement (p=9.40×10-04). At a median follow-up of 51 and 32 months for AYAs and adults, respectively, no statistical difference in terms of 3 and 5-years overall survival (OS) and event-free survival (EFS) was shown. Using the Kaplan-Meier method, in AYAs, the ABVD regimen has an impact on 3-years EFS (p=4.63×10-02). The 36Gy RT was associated with the best 3-years EFS (p=9.24×10-03). Besides, AYA patients with advanced-stage had the worst 3-years OS (76%) (p=2.41×10-02). Although the adolescents and young adults shared similar clinical presentation, we noted that the adolescent group had the worst 3-years EFS (48%), but the best 3-years OS (91%). We identified 15% of primary refractory patients and a rate of toxicity of 5.3% in AYA. CONCLUSION: The treatment approach used is well tolerated by adult patients. However, the AYA patients and particularly adolescent subgroup had more advanced disease at diagnosis and should be treated more intensively in dedicated units. RT dose<36Gy and ABVD chemotherapy were associated with lower EFS in this population.


Assuntos
Doença de Hodgkin/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Mecloretamina/administração & dosagem , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Dosagem Radioterapêutica , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Tunísia/epidemiologia , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto Jovem
7.
Leuk Res ; 90: 106311, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32050133

RESUMO

INTRODUCTION: The optimal management of elderly patients (pts) with Hodgkin's lymphoma is not yet defined. The aims of the present study were: 1) to evaluate clinical and laboratory characteristics of elderly pts; 2) to indentify risk factors for unfavorable outcome. PATIENTS AND METHODS: The outcome of 182 pts ≥ 60 years (y) was retrospectively analyzed (median age, 67y). Mixed cellularity histology was diagnosed in 49.5 %, advanced stage of disease was in 68.7 % pts, CIRS > 3 in 35.7 %, ECOG PS ≥ 2 in 22.9 % (60-69y) of pts. Chemotherapy (CMT) alone was used in 69.2 % and combination of CMT and radiotherapy in 26.9 % of pts. Anthracycline-based CMT received 83.5 % of pts. The median follow-up was 4.5y. RESULTS: The overall response/complete remission rate was 85.6/70.7 %. The median progression free survival (PFS) and overall survival (OS) were 10y and 11.3y, respectively. Estimated 5-y PFS and 5-y OS were 65.7 % (in contrast to 98.2 % in pts < 60y; p < 0.001) and 70.5 % (99.4 % in pts < 60y; p < 0.001). Overall 70 (38.5 %) elderly pts died. The independent risk factors for a shorter OS included CIRS > 3, lymphopenia < 8 % and anthracycline-free CMT, for a shorter PFS anthracycline-free CMT and lymphopenia < 8 %. CONCLUSION: CIRS > 3, lymphopenia < 8 % and anthracycline-free chemotherapy appear to be significant for unfavorable outcome.


Assuntos
Doença de Hodgkin/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , República Tcheca/epidemiologia , Gerenciamento Clínico , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Vigilância em Saúde Pública , Sistema de Registros , Resultado do Tratamento
8.
Ann Hematol ; 99(3): 549-555, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31980860

RESUMO

To evaluate the outcomes of refractory/relapsed cHL patients after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in Beijing Cancer hospital and to identify the prognostic risk factors. We retrospectively analyzed 115 relapsed/refractory cHL patients who accepted HDCT and ASCT in our cancer center and had complete follow-up data from April 2000 to May 2017. Ages of these 115 patients at ASCT ranged from 14 to 63 (median age 28). Forty-four (38.3%) patients achieved CR and 50 (43.5%) patients achieved PR before ASCT. Thirty-seven (48.7%) patients of those 76 patients who did PET-CT before ASCT had negative PET-CT scans. The median follow-up time was 72 months. A total of 23 patients died in our study. The 5-year OS and PFS rates of all patients after ASCT were 78.7% and 53%, respectively. The 5-year OS rates after ASCT of patients who were in CR or PR or less than PR status before ASCT were 92.8%, 68.2%, and 76.2%, respectively (log-rank = 2.913, p = 0.233). And their 5-year PFS rates after ASCT were 69.2%, 54.2%, and 18.5%, respectively (log-rank = 13.615, p = 0.001). Univariate analysis revealed that ECOG (p = 0.010; hazard ratio = 1.578), disease status before ASCT (CR: p = 0.001; hazard ratio = 0.227) and after ASCT (CR: p < 0.001; hazard ratio = 0.154), and PET-CT results after ASCT (p = 0.023; hazard ratio = 0.438) significantly impact patients' PFS while number of pretransplant salvage chemotherapy (p = 0.037; hazard ratio = 2.521), radiotherapy (p = 0.046; hazard ratio = 0.423), and disease status after ASCT (CR: p = 0.010; hazard ratio = 0.197) significantly affected patients' OS. Multivariate analysis shown only disease status before ASCT (p = 0.002) had significant impact on PFS and disease status after ASCT (p = 0.021) had significant impact on OS. R/R HL patients can still obtain long-term PFS after HDCT and ASCT and disease status before ASCT was the most significant prognostic factor for PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Transplante de Células-Tronco , Adolescente , Adulto , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
9.
Ann Hematol ; 99(2): 265-276, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897675

RESUMO

Autologous stem cell transplantation (autoSCT) can achieve long-term remission in primary refractory or relapsed Hodgkin lymphoma (r/r HL); however, still up to 50% of patients relapse after autoSCT. In this retrospective analysis, we investigated the impact of autologous stem cell transplantation in a consecutive, unselected cohort of primary refractory and relapsed Hodgkin lymphoma patients (n = 66) with the majority of patients treated in the pre-brentuximab vedotin and immune checkpoint inhibitor era. In our cohort, a 5-year overall survival (OS) from autoSCT of 59.5% and a 5-year progression-free survival (PFS) after autoSCT of 46.1% was achieved. Multivariate analysis revealed primary refractory disease and early relapse (< 12 months) after initial therapy as well as the presence of B symptoms at relapse as independent risk factors associated with a higher risk for relapse and an inferior PFS and OS. Several other clinical factors, including the presence of extranodal disease at relapse and failure to achieve a complete response to salvage chemotherapy, were associated with a trend towards an inferior survival. Patients relapsing after autoSCT had a particularly poor outcome, regardless of eligibility to undergo allogeneic stem cell transplantation (alloSCT). We further evaluated recently published prognostic models for r/r HL patients undergoing autoSCT and could validate several risk scores in our independent "real world" cohort.


Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
10.
Ann Hematol ; 99(2): 293-299, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897678

RESUMO

The objective of this study is to investigate the prognostic value of the percentage change of maximum standardized uptake value (ΔSUVmax) assessed by PET/CT scan after 2 cycles of chemotherapy (iPET2) in patients with classic Hodgkin's lymphoma (CHL). ΔSUVmax was calculated as follows: the ratio of (SUVmax at baseline-SUVmax at iPET2)/SUVmax at baseline which was determined before initiation of ABVD chemotherapy. The median ΔSUVmax of 46 patients at iPET2 was 87.9% (range - 6.1-100.0%). The optimal ΔSUVmax cutoff value for progression-free survival (PFS) was 83.0% with the receiver operating characteristic curve. The area under the curve for PFS was 0.886 (95% CI 0.788-0.984, p < 0.001). The median PFS of 29 (63.0%) patients who achieved a SUVmax reduction of more than 83.0% was 34 months. The median PFS of 17 (37.0%) patients with ΔSUVmax < 83.0% was 9 months. This difference was significant (p < 0.001). Cohen's kappa coefficient of Deauville Score (DS)- and ΔSUVmax-judged positivity was 0.752 (95% CI 0.592-0.992, p < 0.001), suggesting a strong consistency. Multivariate analysis showed that ΔSUVmax at iPET2 less than 83.0% of SUVmax at diagnosis was an independent factor predicting PFS [HR = 11.339, 95% CI 2.485-51.742, p = 0.002]. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ΔSUVmax<83.0% was 84.6%, 81.8%, 67.7%, 93.1%, and 82.6%, which was similar to that of DS as 61.5%, 87.9%, 66.7%, 85.3%, and 80.4%, respectively. ΔSUVmax<83.0% of iPET2 effectively predicts prognosis of patients with CHL treated with ABVD.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Vimblastina/administração & dosagem
11.
Ann Hematol ; 99(2): 255-264, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897676

RESUMO

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Proteínas de Neoplasias/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína C-Reativa/metabolismo , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
12.
Pediatr Blood Cancer ; 67(4): e28167, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31925920

RESUMO

We describe 12 pediatric patients (8-16 years) with primary refractory (N = 6) or first relapse (N = 6) Hodgkin lymphoma (HL) treated with ifosfamide, gemcitabine, and vinorelbine (IGEV). The overall response rate to IGEV was 100%, with seven (58%) complete responses (CR) and five (42%) partial responses. Successful CD34+ stem cell mobilization was achieved in all patients. Following subsequent autologous stem cell transplantation, 10 patients (83%) achieved CR. At a median follow-up of 71 months, 11 patients had no evidence of disease. Five-year second event-free survival and overall survival were 83% ± 11.0% and 90.0% ± 9.5%, respectively. IGEV is an effective salvage regimen for children with relapsed/refractory HL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas , Doença de Hodgkin , Terapia de Salvação , Transplante de Células-Tronco , Adolescente , Autoenxertos , Criança , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Ifosfamida/administração & dosagem , Masculino , Taxa de Sobrevida , Vinorelbina/administração & dosagem
13.
Pediatr Blood Cancer ; 67(2): e28058, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31724304

RESUMO

BACKGROUND: Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center. PROCEDURE: Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18 FDG-PET-CT-based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late-response assessment [LRA]) if not in complete response (CR; Deauville < 4) at ERA. Stages IA/IB/IIA were low risk (LR) and received two cycles of ABVD (adriamycin/bleomycin/vinblastine/dacarbazine). Stages IAX/IBX/IIAX/IIB/IIIA were intermediate risk (IR), and stages IIBE/IIBX/IIIAE/IIIAX/IIIB/IVA/IVB were high risk (HR). Both received two cycles of OEPA (oncocristine/etoposide/prednisolone/adriamycin). Those in ERA-CR received two cycles of ABVD if LR, and two and four cycles of COPDac (cyclophosphamide/oncocristine/prednisolone/dacarbazine), respectively, for IR and HR. Involved-field radiotherapy (IFRT) was given to bulky sites and ERA < CR. Those at LRA < CR (Deauville < 3) or progression at any stage received salvage regimens. RESULTS: In the study period, 126 patients were identified who received the above protocol. There were 12 LR, and 114 advanced staged Hodgkin lymphoma (AHL) (18, IR; 96, HR) of which 91 (79.8%) had bulky sites. Eight (66.6%) LR and 93 (83%) AHL patients achieved ERA-CRs. IFRT was given to 4 (33.3%) LR patients with ERA < CR, and 92 (80.7%) of AHL (91 bulky sites; 1 ERA < CR). At a median follow-up of 31 months (range, 17-62), three-year event-free survival (EFS) and overall survival (OS) were both 100% for LR, and 94.4% (95% CI, 66.0%-99.2%) for IR, whereas for HR it was 90.3% (95% CI, 82.2%-94.8%) and 92.6% (95% CI, 85.2%-96.4%), respectively. CONCLUSIONS: Children with HL have favorable outcomes with manageable toxicities when treated on a risk-stratified and adapted approach. A high proportion of AHL have bulky disease necessitating IFRT, a concern that will have to be factored in future strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Centros de Atenção Terciária/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Humanos , Índia , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Ann Hematol ; 99(2): 277-282, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872362

RESUMO

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Transplante de Células-Tronco , Adulto , Autoenxertos , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Taxa de Sobrevida , Vimblastina/administração & dosagem
15.
Ann Hematol ; 99(2): 301-307, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31844933

RESUMO

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.


Assuntos
Brentuximab Vedotin/administração & dosagem , Doença de Hodgkin , Transplante de Células-Tronco , Adulto , Aloenxertos , Autoenxertos , Brentuximab Vedotin/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida
16.
Ann Hematol ; 99(2): 283-291, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872361

RESUMO

FDG-positron emission tomography (PET) performed early during therapy in advanced Hodgkin lymphoma patients has been confirmed as being important for progression-free survival. A group of patients with a negative interim-PET (i-PET) showed a positive end induction PET (e-PET). The aim of this study was to evaluate the clinical characteristics of patients with a positive e-PET as a secondary end point of the HD0801 study. A total of 519 patients with advanced-stage de novo Hodgkin lymphoma received initial treatment and underwent an i-PET. Patients with negative results continued the standard treatment. i-PET negative patients were then evaluated for response with an e-PET and those patients found to have a positive one were also then given a salvage therapy. Among 409 i-PET negative, 16 interrupted the therapy, 393 patients were evaluated with an e-PET, and 39 were positive. Sixteen out of 39 underwent a diagnostic biopsy and 15 were confirmed as HD. Seventeen out of 39 e-PET were reviewed according to the Deauville Score and, in sixteen, it was confirmed positive (10 DS 5, 6 DS 4). With the exception of high LDH value at diagnosis (p = 0.01; HR 95% CI 1.18-4.89), no clinical characteristics were significantly different in comparison with e-PET negative patients. Positive e-PET after a negative i-PET has a worse outcome when compared with i-PET positive patients salvaged with therapy intensification. It was not possible to identify clinical characteristics associated with a positive e-PET.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fluordesoxiglucose F18/administração & dosagem , Doença de Hodgkin , Tomografia por Emissão de Pósitrons , Transplante de Células-Tronco , Adulto , Autoenxertos , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Estudos Prospectivos , Taxa de Sobrevida , Vimblastina/administração & dosagem
17.
Anticancer Res ; 39(12): 6859-6862, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810953

RESUMO

BACKGROUND/AIM: Hodgkin's lymphoma (HL) accounts for 1% of cancers and is of largely unknown pathogenesis. This study intended to find clues about potential causes (etiology) of HL through observations on patients and their families. PATIENTS AND METHODS: In 37 years of a medical oncology practice in Basel, Switzerland, 36 out of 2201 patients (1.6%) had HL. Etiological information has been obtained from the patients with the help of a German translation of the NCI Medical History Questionnaire for Cancer Etiology, and through the study of their medical charts. RESULTS: Findings of etiological interest were observed in the medical history of 26 out of the 36 patients with HL; these findings were grouped as follows: benign tumors (25%), carcinogenic exposures (19%), immunologic disorders (19%), secondary malignancies (14%), infections (11%), congenital disorders (8%) and tonsillectomies (6%). Twenty-two out of 36 patients had one or more relatives with cancer. CONCLUSION: Personal and family history of patients with HL is a readily available useful tool for etiology research. The fact that HL is frequently associated with other cancers in patients and their relatives points to causal genetic factors.


Assuntos
Doença de Hodgkin/etiologia , Doença de Hodgkin/mortalidade , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Anamnese , Pessoa de Meia-Idade , Fatores de Risco , Suíça/epidemiologia , Adulto Jovem
18.
Blood Cancer J ; 9(12): 100, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827067

RESUMO

Effective salvage options inducing high complete metabolic response (CMR) rates without significant toxicity are needed for Hodgkin lymphoma (HL) patients failing induction treatment and who are candidate to autologous stem cell transplantation (ASCT). Brentuximab vedotin (BV) and bendamustine are active monotherapies in the relapsed/refractory setting and their combination (the BBV regimen) possibly enhances their activity. This single-arm multicenter phase 2 study investigated the efficacy and safety of BBV as first salvage therapy in 40 patients with relapsed/refractory HL. Thirty-eight patients were evaluable for efficacy: 30 (78.9%) had a CMR and 2 (5.3%) a partial response, leading to an overall response rate (ORR) of 84.2%. The ORR in the primary refractory subset was 75.0%, among relapsed patients it was 94.4%. Thirty-five patients could mobilize peripheral blood stem cells and 33 underwent ASCT. At a median follow-up of 23 months, the estimated 3-year overall survival and progression-free survival are 88.1% and 67.3%. During therapy, only 3 grade IV cases of neutropenia occurred and resolved within a week. No grade 4 extrahematologic toxicities were reported; skin reactions were however rather frequent (65%). These results suggest that the BBV regimen exhibits promising efficacy and a manageable toxicity in a challenging subpopulation of HL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina , Brentuximab Vedotin , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Terapia de Salvação , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
19.
Lancet Haematol ; 6(11): e551-e561, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31564649

RESUMO

BACKGROUND: Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS: We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS: Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION: Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING: European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic.


Assuntos
Doença de Hodgkin/diagnóstico , Adulto , Antineoplásicos/uso terapêutico , Parto Obstétrico , Intervalo Livre de Doença , Feminino , Idade Gestacional , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Nascimento Vivo , Gravidez , Cuidado Pré-Natal , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
In Vivo ; 33(5): 1599-1604, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471410

RESUMO

BACKGROUND/AIM: Methotrexate (MTX)-associated classical Hodgkin lymphoma (CHL) is a rare disease, and its prognosis remains unclear. MATERIALS AND METHODS: Our study retrospectively compared clinicopathological features and clinical outcomes of patients with MTX-CHL (n=6) and sporadic CHL (n=40). RESULTS: MTX-CHL was more frequently the mixed cellularity subtype and positive for Epstein-Barr virus, but less frequently positive for CD20 than sporadic CHL. Clinically, MTX-CHL was more frequent in advanced stage than sporadic CHL and often associated with extranodal disease. After the cessation of MTX, transient spontaneous regression was observed in two MTX-CHL cases. Eventually, all patients with MTX-CHL required chemotherapy, which gave similar complete remission rates at 2 years compared to sporadic CHL. Patients with MTX-CHL tended to have a higher incidence of grade 3 or more neutropenia. CONCLUSION: The present study revealed differences in clinicopathological features but similarities in clinical outcomes of MTX-CHL and sporadic CHL.


Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/etiologia , Imunossupressores/efeitos adversos , Metotrexato/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Imunossupressores/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Avaliação de Sintomas , Adulto Jovem
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