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1.
BMJ Case Rep ; 17(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569735

RESUMO

A male patient in his 60s was admitted to our hospital with symptoms of dyspnoea, asthenia, diaphoresis and acute kidney failure. No tumour or infection was detected in initial screening. However, laboratory examination suggested that the acute kidney failure was due to an intrarenal cause, exhibiting a tubular injury pattern and indications of tumour lysis syndrome. Initial hydration therapy, paired with intravenous rasburicase, rapidly improved the kidney function. Unfortunately, the kidney function deteriorated once again, prompting a kidney biopsy that revealed an aggressive diffuse large B-cell non-Hodgkin lymphoma of the kidney. The chemotherapy, comprised of R-CHOP scheme, led to a full recovery of the kidney function and complete remission of the lymphoma. Primary renal non-Hodgkin lymphoma without nodal manifestation is rare, and its pathophysiology is poorly understood. Therapy schemes can vary significantly between cases, relying primarily on non-renal-specific haemato-oncological guidelines. Therefore, further studies are needed to develop the best therapeutic approaches.


Assuntos
Injúria Renal Aguda , Linfoma não Hodgkin , Masculino , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Rim/diagnóstico por imagem , Rim/patologia , Injúria Renal Aguda/diagnóstico , Vincristina/uso terapêutico , Rituximab/uso terapêutico
2.
Biomolecules ; 14(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38672512

RESUMO

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 µM to 50 µM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.


Assuntos
Benzoxazinas , Canabidiol , Sobrevivência Celular , Dronabinol , Linfoma não Hodgkin , Morfolinas , Naftalenos , Humanos , Cães , Canabidiol/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dronabinol/farmacologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Benzoxazinas/farmacologia , Naftalenos/farmacologia , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Endocanabinoides/farmacologia , Endocanabinoides/metabolismo
3.
Nat Commun ; 15(1): 2608, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521835

RESUMO

Identifying sex differences in outcomes and toxicity between males and females in oncology clinical trials is important and has also been mandated by National Institutes of Health policies. Here we analyze the Trialtrove database, finding that, strikingly, only 472/89,221 oncology clinical trials (0.5%) had curated post-treatment sex comparisons. Among 288 trials with comparisons of survival, outcome, or response, 16% report males having statistically significant better survival outcome or response, while 42% reported significantly better survival outcome or response for females. The strongest differences are in trials of EGFR inhibitors in lung cancer and rituximab in non-Hodgkin's lymphoma (both favoring females). Among 44 trials with side effect comparisons, more trials report significantly lesser side effects in males (N = 22) than in females (N = 13). Thus, while statistical comparisons between sexes in oncology trials are rarely reported, important differences in outcome and toxicity exist. These considerable outcome and toxicity differences highlight the need for reporting sex differences more thoroughly going forward.


Assuntos
Neoplasias Pulmonares , Linfoma não Hodgkin , Estados Unidos , Feminino , Humanos , Masculino , Rituximab/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
Viruses ; 16(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38543695

RESUMO

It has been suggested that the effect of coronavirus disease 2019 (COVID-19) booster vaccination in patients with B-cell non-Hodgkin's lymphoma (B-NHL) is inferior to that in healthy individuals. However, differences according to histological subtype or treatment status are unclear. In addition, there has been less research on patients who subsequently develop breakthrough infections. We investigated the effects of the first COVID-19 booster vaccination for patients with B-NHL and the clinical features of breakthrough infections in the Omicron variant era. In this study, B-NHL was classified into two histological subtypes: aggressive lymphoma and indolent lymphoma. Next, patients were subdivided according to treatment with anticancer drugs at the start of the first vaccination. We also examined the clinical characteristics and outcomes of patients who had breakthrough infections after a booster vaccination. The booster effect of the COVID-19 mRNA vaccine in patients with B-NHL varied considerably depending on treatment status at the initial vaccination. In the patient group at more than 1 year after the last anticancer drug treatment, regardless of the histological subtype, the booster effect was comparable to that in the healthy control group. In contrast, the booster effect was significantly poorer in the other patient groups. However, of the 213 patients who received the booster vaccine, 22 patients (10.3%) were infected with COVID-19, and 18 patients (81.8%) had mild disease; these cases included the patients who remained seronegative. Thus, we believe that booster vaccinations may help in reducing the severity of Omicron variant COVID-19 infection in patients with B-NHL.


Assuntos
COVID-19 , Linfoma não Hodgkin , Linfoma , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Vacinas de mRNA , Infecções Irruptivas , Estudos de Coortes , SARS-CoV-2/genética , RNA Mensageiro , Linfoma não Hodgkin/tratamento farmacológico , Vacinação , Anticorpos Antivirais
5.
Eur J Oncol Nurs ; 69: 102540, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38461728

RESUMO

PURPOSE: This study aimed to explore the incidence and severity of vincristine-induced peripheral neuropathy (VIPN) in non-Hodgkin lymphoma (NHL) survivors (primary aim) and its impact on daily life by comparing common cancer symptoms, functional status, and quality of life (QoL) among survivors with acute, long-term, and non-VIPN (secondary aim). METHODS: This cross-sectional study examined 144 NHL survivors. Standardized questionnaires were used to assess common cancer symptoms, functional status, and QoL with the European Organization for the Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC-QLQ-C30). VIPN (Chemotherapy-Induced Peripheral Neuropathy) status was classified using EORTC-QLQ-CIPN20. A self-designed interference scale was developed to determine the impact of the VIPN on daily activities. The Kruskal-Wallis test and Spearman rank correlation were used in this study. RESULTS: Among the survivors of acute and long-term VIPN, the highest incidences and most severe symptoms were found for hand numbness and foot cramps. A significant moderate correlation was found between disturbances in daily activities and acute or long-term VIPN, including gait changes, going up or down the stairs, and imbalance-related falls. Acute and long-term VIPN survivors showed worse symptoms (fatigue, insomnia, and constipation) and lower QoL than non-VIPN survivors did. In acute VIPN, social function was significantly affected, whereas in long-term VIPN, emotional and cognitive functions were affected. CONCLUSION: Numbness and cramps should be addressed in survivors of acute and long-term VIPN. Preventing falls is recommended for NHL survivors with VIPN, and psychological support is suggested for long-term VIPN survivors.


Assuntos
Linfoma não Hodgkin , Neoplasias , Doenças do Sistema Nervoso Periférico , Humanos , Vincristina/efeitos adversos , Qualidade de Vida/psicologia , Estudos Transversais , Estado Funcional , Hipestesia , Cãibra Muscular , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/psicologia , Sobreviventes , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia
6.
Front Immunol ; 15: 1303310, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533514

RESUMO

Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules' expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Transcriptoma , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Microambiente Tumoral
7.
PLoS One ; 19(3): e0300330, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38466704

RESUMO

BACKGROUND: The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. METHODS: The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. RESULTS: Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). CONCLUSION: Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.


Assuntos
Linfoma não Hodgkin , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Estudos Retrospectivos , Incidência , Programa de SEER , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/tratamento farmacológico , Prognóstico
8.
Adv Drug Deliv Rev ; 207: 115193, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38311111

RESUMO

The favorable benefit-risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An integrated, fit-for-purpose clinical pharmacology package was designed to support regulatory approval. To address key clinical pharmacology questions without dedicated clinical pharmacology studies, we leveraged non-clinical and clinical data for polatuzumab vedotin, published clinical data for brentuximab vedotin, a similar antibody-drug conjugate, and physiologically based pharmacokinetic and population pharmacokinetic modeling approaches. We review strategies and model-informed outcomes that contributed to regulatory approval of polatuzumab vedotin plus bendamustine and rituximab in R/R DLBCL. These strategies made polatuzumab vedotin available to patients earlier than previously possible; depending on the strength of available data and the regulatory/competitive environment, they may also prove useful in accelerating the development of other agents.


Assuntos
Imunoconjugados , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Farmacologia Clínica , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico
9.
Surg Oncol Clin N Am ; 33(2): 447-466, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401918

RESUMO

Although there are more than 100 clinically distinct lymphoid neoplasms with varied prognoses and treatment approaches, they generally share high sensitivity to glucocorticoids, cytotoxic chemotherapy, and radiation. The disease control rates for lymphoid malignancies are higher than many solid tumors, and many are curable even when presenting with extensive involvement. Novel targeted therapies have improved disease control and cure rates for nearly all subtypes of lymphoid neoplasms. Surgical oncologists will primarily be involved in obtaining biopsies of sufficient quality to allow accurate diagnosis. However, there are scenarios in which surgical intervention may be necessary to address an oncologic emergency.


Assuntos
Linfoma não Hodgkin , Linfoma , Mieloma Múltiplo , Cirurgiões , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Linfoma/terapia , Prognóstico
10.
Cell Rep Med ; 5(2): 101414, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38330942

RESUMO

ADG106, a ligand-blocking agonistic antibody targeting CD137 (4-1BB), exhibits promising results in preclinical studies, demonstrating tumor suppression in various animal models and showing a balanced profile between safety and efficacy. This phase 1 study enrolls 62 patients with advanced malignancies, revealing favorable tolerability up to the 5.0 mg/kg dose level. Dose-limiting toxicity occurs in only one patient (6.3%) at 10.0 mg/kg, resulting in grade 4 neutropenia. The most frequent treatment-related adverse events include leukopenia (22.6%), neutropenia (22.6%), elevated alanine aminotransferase (22.6%), rash (21.0%), itching (17.7%), and elevated aspartate aminotransferase (17.7%). The overall disease control rates are 47.1% for advanced solid tumors and 54.5% for non-Hodgkin's lymphoma. Circulating biomarkers suggest target engagement by ADG106 and immune modulation of circulating T, B, and natural killer cells and cytokines interferon γ and interleukin-6, which may affect the probability of clinical efficacy. ADG106 has a manageable safety profile and preliminary anti-tumor efficacy in patients with advanced cancers (this study was registered at ClinicalTrials.gov: NCT03802955).


Assuntos
Linfoma não Hodgkin , Neoplasias , Neutropenia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Anticorpos Monoclonais , Resultado do Tratamento
11.
Braz J Med Biol Res ; 57: e13284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359273

RESUMO

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.


Assuntos
Anticorpos Monoclonais Humanizados , Linfoma não Hodgkin , Humanos , Infusões Intravenosas , Linfoma não Hodgkin/tratamento farmacológico , Estudos Prospectivos , Centros de Atenção Terciária
12.
Adv Ther ; 41(3): 1226-1244, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38302846

RESUMO

INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used. METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen. RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% with ≥ 2 and ≥ 3 prior LOTs, respectively). Median duration of follow-up was 7.7 months. Most patients (57.1%) were male; mean standard deviation (SD) age was 63 (14.7) years. Overall and complete response rates (95% confidence interval (CI) were 52% (48-56) and 23% (19-27). Median duration of response and duration of complete response were 3.5 and 18.4 months. Median progression-free and overall survival (95% CI) was 3.0 (2.8-3.3) and 12.9 (10.1-16.9) months, respectively. Patients with a higher number of prior LOTs, primary refractoriness, refractoriness to last LOT, refractoriness to last anti-CD20-containing regimen, and prior CAR T exposure had worse outcomes (i.e., challenging-to-treat R/R DLBCL) compared with those without these characteristics. CONCLUSIONS: Outcomes in patients with R/R DLBCL treated with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents remain poor, especially for those with challenging-to-treat R/R DLBCL. These findings underscore the unmet need for new, safe, and effective therapies, especially for challenging-to-treat R/R DLBCL populations.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Rituximab/uso terapêutico , Lenalidomida/uso terapêutico , Estudos Retrospectivos , Padrão de Cuidado , Linfoma não Hodgkin/tratamento farmacológico , Resultado do Tratamento , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Análise de Dados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
13.
Cancer Med ; 13(2): e6965, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38348996

RESUMO

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. METHODS: A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. RESULTS: Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). CONCLUSIONS: The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Humanos , Carmustina/efeitos adversos , Gencitabina , Transplante de Células-Tronco Hematopoéticas/métodos , Melfalan/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo/métodos , Linfoma não Hodgkin/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Etoposídeo/efeitos adversos , Citarabina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Condicionamento Pré-Transplante/métodos
14.
Medicine (Baltimore) ; 103(7): e37100, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363899

RESUMO

Lymphoblastic lymphoma (LBL) is a rare, aggressive non-Hodgkin lymphoma (NHL) that has no established therapeutic approaches. The aim of this study was to investigate optimal treatments and prognostic risk models for patients with LBL in East Asia. We retrospectively examined the clinical data and treatment courses of adult patients diagnosed as LBL by WHO 2017 classification system. Median overall survival (OS) of the 78 patients with LBL was 38.3 months. There was no significant difference in OS between the patients who were treated with acute lymphoblastic leukemia (ALL)-like protocols and with NHL-like protocols (72.4 months vs 37.5 months, respectively, P = .546). The patients treated with ALL-like protocols had significantly shorter progression-free survival (PFS) (median 11.7 months for ALL-like protocols vs 27.0 months for NHL-like protocols, P = .030). A multivariable analysis found that central nervous system (CNS) prophylaxis, relapse of CNS lesions, leukemic transformation, and response to initial treatment were risk factors for OS of patients with LBL. Hematopoietic stem cell transplantation had no survival benefit, compared with chemotherapy-only treatment. Less intensive chemotherapy may be more optimal for patients in East Asia. Prophylaxis and management of CNS lesions should be emphasized throughout the treatment of LBL.


Assuntos
Linfoma não Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ásia Oriental/epidemiologia
16.
Future Oncol ; 20(2): 71-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38179936

RESUMO

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov).


Assuntos
Linfoma não Hodgkin , Humanos , Estudos Prospectivos , Linfoma não Hodgkin/tratamento farmacológico , Resultado do Tratamento , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto
17.
Can J Diabetes ; 48(3): 195-203.e1, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38211830

RESUMO

OBJECTIVES: The aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described. METHODS: We conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities. RESULTS: Our cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts. CONCLUSIONS: Hyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration.


Assuntos
Diabetes Mellitus , Glucocorticoides , Neoplasias Hematológicas , Hiperglicemia , Humanos , Feminino , Hiperglicemia/epidemiologia , Hiperglicemia/induzido quimicamente , Hiperglicemia/mortalidade , Masculino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Idoso , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Adulto , Estudos de Coortes , Ontário/epidemiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/epidemiologia
18.
Ann Hematol ; 103(5): 1635-1642, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38246951

RESUMO

Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4-29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Sulfonamidas , Realidade Virtual , Humanos , Pessoa de Meia-Idade , Prednisona , Vincristina , Etoposídeo , Anticorpos Monoclonais Murinos , Ciclofosfamida , Rituximab , Linfoma não Hodgkin/tratamento farmacológico , Doxorrubicina , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
20.
Blood Cancer J ; 14(1): 23, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38272863

RESUMO

Bispecific antibodies (BsAbs) are a new group of targeted therapies that are revolutionizing the treatment landscape of B-cell non-Hodgkin's lymphoma (B-NHL). In the relapsed/refractory setting, salvage chemotherapy and autologous stem cell transplantation are capable of curing 50% of patients, whereas the other half will have a dismal outcome with a median overall survival of less than 12 months. This unmet need reinforced the importance of innovative therapies like the BsAbs and CAR-T cell therapies. In this review, we delve into BsAbs in B-NHL from the preclinical development to clinical data in both refractory and frontline settings, and then discuss future perspectives.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B , Linfoma não Hodgkin , Humanos , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo , Linfoma não Hodgkin/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Terapia de Salvação
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