RESUMEN

BACKGROUND: Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. METHODS: This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). FINDINGS: Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24-42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65-0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45-0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6-96·1) for BrECADD and 90·9% (88·7-93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7-99·5) and 98·2% (97·2-99·3), respectively. INTERPRETATION: BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma. FUNDING: Takeda Oncology.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/efectos adversos , Brentuximab Vedotina/uso terapéutico , Ciclofosfamida/uso terapéutico , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Dacarbazina/uso terapéutico , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/mortalidad , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Resultado del Tratamiento

RESUMEN

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches.

RESUMEN

Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Enfermedades Pulmonares , Humanos , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Femenino , Masculino , Adulto , Dinamarca/epidemiología , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Anciano , Bleomicina/efectos adversos , Bleomicina/administración & dosificación , Adulto Joven , Incidencia , Procarbazina/efectos adversos , Procarbazina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Estudios de Cohortes , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Adolescente , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación

RESUMEN

PURPOSE: Patients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS). PATIENTS AND METHODS: This study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort). RESULTS: In total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis. CONCLUSION: The new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI.

Asunto(s)

Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/terapia , Supervivencia sin Enfermedad , Área Bajo la Curva , Aprendizaje Automático , Supervivencia sin Progresión

RESUMEN

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

Asunto(s)

Variaciones en el Número de Copia de ADN , Linfoma de Células B Grandes Difuso , Humanos , Estudios Retrospectivos , Perfil Genético , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Proteínas Adaptadoras Transductoras de Señales/genética

RESUMEN

Identifying risk factors for intensive care unit (ICU) admission in acute leukemia (AL) patients may guide decision-making and improve prognosis. We included all adult AL patients receiving high-intensive chemotherapy in Denmark from 2005 to 2016. We examined risk factors [crude and adjusted (a) relative risks (RRs) with 95% confidence intervals (CI)] and calculated RRs of death after 1-, 3-, and 5-years in ICU-admitted patients compared with matched cohorts. In 1417 AML and 306 ALL patients, the 1-year risk of ICU admission was 28.1% for AML and 26.4% for ALL patients, with the majority related to the first course of chemotherapy. Performance status >1 was associated with increased risk. The 1-year mortality was higher in ICU-admitted patients (AML: 69.7 vs. 35.0% [aRR 2.74;CI = 2.17-3.47]; ALL 65.0 vs. 20.0% [aRR 3.04;CI = 1.54-6.02]). The excess mortality decreased with time. In this study, performance status was associated with increased risk of ICU admission and identifies high-risk patients. ICU admission was associated with high mortality, especially within the first year.

Asunto(s)

Unidades de Cuidados Intensivos , Leucemia Mieloide Aguda , Enfermedad Aguda , Adulto , Estudios de Cohortes , Dinamarca/epidemiología , Mortalidad Hospitalaria , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

We analysed a large cohort of Hodgkin lymphoma (HL) patients in order to characterize: (1) the pattern of late recurrence of lymphoid malignancies (LR) after initial treatment for HL over a 35-year period; (2) the clinicopathological parameters influencing the risk of LR; and (3) the outcome of patients experiencing LR. We reviewed data of 3350 HL patients diagnosed in Denmark between 1982 and 2018 and registered in the Danish National Lymphoma Registry (LYFO). LR was defined as a recurrence of lymphoid malignancy at least five years after initial diagnosis. LR occurred in 58 patients, with a cumulative incidence at 10, 15 and 20 years of 2.7%, 4.0% and 5.4% respectively. LR was more frequently observed in patients with nodular lymphocyte-predominant HL (NLPHL) [hazard ratio (HR) 4.5; 95% confidence interval (CI): 2.4-8.4, p < 0.001]. In classical HL (cHL) patients, older age and lymphocytopenia were risk factors for LR with HRs of 1.04 per additional year (95% CI: 1.02-1.06) and 5.6 (95% CI: 2.7-11.5) respectively. Mixed cellularity histological subtype was a risk factor for LR, but only in females, with a HR of 5.4 (95% CI: 1.4-20.4, p = 0.014). In contrast to what was observed in NLPHL, LR in cHL was associated with an almost threefold increased risk of death compared with patients in continuous complete remission. Approximately one fifth (22.4%) of patients with LR experienced a second relapse.

Asunto(s)

Enfermedad de Hodgkin , Linfoma , Dinamarca/epidemiología , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/terapia , Humanos , Recurrencia Local de Neoplasia , Sistema de Registros

RESUMEN

In classic Hodgkin lymphoma (cHL), the tumour microenvironment (TME) is of major pathological relevance. The paucity of neoplastic cells makes it important to study the entire TME when searching for prognostic biomarkers. Cure rates in cHL have improved markedly over the last several decades, but patients with primary refractory disease still show inferior survival. We performed a proteomic comparison of pretreatment tumour tissue from ABVD treatment-refractory versus ABVD treatment-sensitive cHL patients, in order to identify biological differences correlating with treatment outcome. Formalin-fixed paraffin-embedded tumour tissues from 36 patients with cHL, 15 with treatment-refractory disease, and 21 with treatment-sensitive disease, were processed for proteomic investigation. Label-free quantification nano liquid chromatography tandem mass spectrometry was performed on the tissues. A total of 3920 proteins were detected and quantified between the refractory and sensitive groups. This comparison revealed several subtle but significant differences in protein expression which could identify subcluster characteristics of the refractory group. Bioinformatic analysis of the biological differences indicated that a number of pathologically activated signal transduction pathways are disturbed in ABVD treatment-refractory cHL.

RESUMEN

Treatment of early relapses of T lymphoblastic leukemia/lymphoma is often unsuccessful. We tested an experimental regimen containing daratumumab and nelarabine in two young patients with early relapses of T lymphoblastic lymphoma and T-ALL, respectively. Both patients achieved a deep complete remission. Combining daratumumab with chemotherapy may have a role in relapsing T lymphoblastic leukemia/lymphoma.

RESUMEN

The 2016 update of the WHO classification update of lymphoid malignancies includes new entities and modifications, which affect current treatment paradigms and provide a framework for new interventional strategies, as summarised in this review. With the increasing understanding of the pathogenetic mechanisms behind lymphoid malignancies involving surface markers, signaling transduction pathways, epigenetic modulations as well as the tumour micro-environment, novel agents and immune therapeutic strategies have been developed. These precision medicine approaches are gradually improving the prognosis of lymphoma patients. Methods reliably assessing the quality of clinical responses also contribute to this general prognostic improvement.

Asunto(s)

Linfoma , Humanos , Linfoma/diagnóstico , Medicina de Precisión , Pronóstico , Microambiente Tumoral

RESUMEN

Recent technological advances have led to an increasing understanding of the pathogenetic mechanisms behind lymphoid malignancies. Based on his new knowledge, novel agents and immune therapeutic strategies have been developed. The combination of diagnostic, therapeutic and surveillance-related precision medicine approaches may eventually represent the key for a substantial improvement in both life expectancy and quality of life, also for those patient groups presently characterised by the highest unmet clinical need, as argued in this review.

Asunto(s)

Neoplasias , Calidad de Vida , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Medicina de Precisión

RESUMEN

PURPOSE: The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care. MATERIALS AND METHODS: All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use. RESULTS: A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 v 57.1; P = .871 for males and 63.8 v 61.2; P = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 v 60.8; P = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% v 6.3%; P < .001; females 13.6% v 5.5%; P = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators. CONCLUSION: The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivientes de Cáncer/estadística & datos numéricos , Preservación de la Fertilidad/estadística & datos numéricos , Enfermedad de Hodgkin/tratamiento farmacológico , Nacimiento Vivo/epidemiología , Padres , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Adolescente , Adulto , Estudios de Casos y Controles , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Pronóstico , Adulto Joven

Asunto(s)

Antígenos CD , Linfoma de Células B Grandes Difuso , Antígenos de Diferenciación Mielomonocítica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Pronóstico , Receptores de Superficie Celular

RESUMEN

BACKGROUND: The programmed cell death protein 1 (PD-1) and its ligand 1 and 2 (PD-L1/PD-L2) regulate the immune system, and the checkpoint pathway can be exploited by malignant cells to evade anti-tumor immune response. Soluble forms (sPD-1/sPD-L1/sPD-L2) exist in the peripheral blood, but their biological and clinical significance is unclear. METHOD: Time-resolved immunofluorometric assay (TRIFMA) and enzyme-linked immunosorbent assay (ELISA) were used to measure sPD-1, sPD-L1, and sPD-L2 levels in serum from 131 lymphoma patients and 22 healthy individuals. RESULTS: Patients had higher sPD-1 and sPD-L2 levels than healthy individuals. In diffuse large B-cell lymphoma, patients with high International Prognostic Index score had higher sPD-1 levels and sPD-L2 levels correlated with subtype according to cell of origin. Compared to other lymphoma types, follicular lymphoma displayed higher sPD-1 and lower sPD-L1 levels along with lower ligand/receptor ratios. CONCLUSION: This is the first study to simultaneously characterize pretherapeutic sPD-1, sPD-L1, and sPD-L2 in a variety of lymphoma subtypes. The relation between higher sPD-1 levels and adverse prognostic factors suggests a possible biological role and potential clinical usefulness of sPD-1. Moreover, the reverse expression pattern in follicular lymphoma and T-cell lymphoma/leukemia may reflect biological information relevant for immunotherapy targeting the PD-1 pathway.

Asunto(s)

Antígeno B7-H1/sangre , Biomarcadores de Tumor/sangre , Regulación Leucémica de la Expresión Génica , Leucemia/sangre , Linfoma de Células B/sangre , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células T/sangre , Proteína 2 Ligando de Muerte Celular Programada 1/sangre , Receptor de Muerte Celular Programada 1/sangre , Adulto , Apoptosis , Antígeno B7-H1/química , Donantes de Sangre , Estudios de Casos y Controles , Recuento de Células , Pruebas Diagnósticas de Rutina , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoterapia , Ligandos , Linfoma de Células B/inmunología , Linfoma de Células B/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Proteína 2 Ligando de Muerte Celular Programada 1/química , Receptor de Muerte Celular Programada 1/química

RESUMEN

BACKGROUND: Nationwide studies of ocular adnexal lymphoma (OAL) are very rare in the literature, and knowledge on incidence, subtype distribution and long-term survival data is limited. This is the largest national study of OAL to date. This study sought to find information on incidence, changes in incidence, clinical findings, distribution of subtypes, survival and prognostic factors. METHODS: Patients diagnosed with OAL from January 1, 1980 to December 31, 2017 were identified in Danish registers, and clinical as well as survival data were collected. The data were analysed with Kaplan-Meier plots and log-rank test. RESULTS: 387 patients were included in the study. The major lymphoma subtypes were extranodal marginal-zone B cell lymphoma (EMZL) (55%), diffuse large B cell lymphoma (DLBCL) (13%), mantle cell lymphoma (MCL) (11%) and follicular lymphoma (FL) (10%). OAL is a disease of the elderly (median age 69 years). The incidence of lymphoma of the ocular adnexal region has increased significantly throughout the time period of the study (Pearson correlation coefficient, r=0.65; P<0.001). In the period 1980-1984, the incidence was 0.086 per 100 000, which increased to 0.307 per 100 000 in the period 2013-2017. Low-grade, low-stage primary lymphomas were treated with radiotherapy, whereas patients with high-stage, high-grade and/or relapsed disease were treated with chemotherapy. Low-grade subtypes EMZL (89%) and FL (56%) had better 10-year disease-specific survival than the high-grade lymphomas DLBCL (38%) and MCL (31%)(p<0.001). CONCLUSION: OAL is increasing in incidence in the Danish population for unknown reasons. However, the prognosis for most OAL is favourable, as highlighted in this national long-term study.

Asunto(s)

Neoplasias de la Conjuntiva/epidemiología , Neoplasias de los Párpados/epidemiología , Enfermedades del Aparato Lagrimal/epidemiología , Linfoma/epidemiología , Neoplasias Orbitales/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Neoplasias de la Conjuntiva/patología , Dinamarca/epidemiología , Supervivencia sin Enfermedad , Neoplasias del Ojo/epidemiología , Neoplasias del Ojo/patología , Neoplasias de los Párpados/patología , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Enfermedades del Aparato Lagrimal/patología , Linfoma/patología , Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma de Células B de la Zona Marginal/patología , Linfoma Folicular/epidemiología , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células del Manto/epidemiología , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Neoplasias Orbitales/patología , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia

RESUMEN

PURPOSE: Contemporary data on mortality of hematological patients admitted to the intensive care unit (ICU) are missing. In a Danish nationwide set-up, we assessed 30-day and 1-year mortality in this population including impact of age and comorbidity, with non-hematological patients as reference. METHODS: This population-based cohort study included all non-surgical patients > 15 years of age admitted to an ICU in Denmark between 2010 and 2015. Data on hematological malignancies were obtained from the Danish Hematological Database, and information on the Charlson Comorbidity Index was obtained from the Danish National Patient Registry. Thirty-day and 1-year mortality was estimated using the Kaplan-Meier method. We used Cox proportional hazards regression to estimate hazard ratios. RESULTS: We included 2122 ICU patients with a hematological malignancy and 88,951 non-hematological ICU patients. The 30-day mortality was 44% (95% confidence interval: 42-47%) among hematological patients and 27% (27-27%) among non-hematological patients. Similarly, 1-year mortality was 66% (64-68%) and 37% (37-37%), respectively. The corresponding hazard ratio with adjustment for age, sex, and comorbidity was 1.62 (1.54-1.71). Excess mortality was observed in all subgroups of age or of comorbidity. For example, the 1-year mortality for patients with Charlson Comorbidity Index Score > 3: 70% (66-74%) among hematological patients and 62% (61-63%) among non-hematological patients. CONCLUSION: ICU patients with hematological malignancy had higher mortality than other ICU patients. However, one third of critically ill patients with a hematological malignancy is alive 1 year after ICU admission.

Asunto(s)

Neoplasias Hematológicas , Unidades de Cuidados Intensivos , Estudios de Cohortes , Enfermedad Crítica , Dinamarca/epidemiología , Neoplasias Hematológicas/terapia , Mortalidad Hospitalaria , Humanos

RESUMEN

The burden of late effects among Hodgkin lymphoma (HL) survivors treated according to contemporary protocols remains poorly characterized. We used nation-wide registers to assess number of inpatient bed-days and specialist outpatient visits among 1048 HL-patients (<25 years, diagnosed 1990-2010) and 5175 country-, sex-, and age-matched comparators. We followed them for up to 24 years, with time-dependent assessment of relapse status. International Classification of Diseases (ICD-10) chapter-specific hazard ratios (HRs) were assessed in Cox regression analyses, and nonparametric statistics described patterns of health-care-use. Relative to comparators, relapse-free survivors were at increased risk of infections, diseases of the blood, endocrine, circulatory and respiratory systems, and unspecific symptoms, HRs ranging from 1.86 to 3.05. Relative to comparators, relapsed survivors had at statistically significantly increased risk of diseases reflecting practically all investigated disease-chapters, HRs ranging from 1.60 to 18.7. Among relapse-free survivors, 10% of the patients accounted for 80% of all hospital bed days, and 55% were never hospitalized during follow-up. Among relapsed-survivors, 10% of the patients accounted for 50% of the bed days, and only 24% were never hospitalized during follow-up. In contrast, 10% of the comparators accounted for 90% of hospital bed days and 75% were never hospitalized. These findings challenge the impression of a uniformly distributed long-term morbidity among all HL survivors and emphasize the need for early identification and attention to patients particularly susceptible to late effects, such as relapsed survivors.

Asunto(s)

Supervivientes de Cáncer/estadística & datos numéricos , Enfermedad de Hodgkin/complicaciones , Hospitalización/estadística & datos numéricos , Adolescente , Niño , Preescolar , Estudios de Cohortes , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/terapia , Humanos , Lactante , Masculino , Recurrencia , Análisis de Regresión , Suecia/epidemiología , Adulto Joven

RESUMEN

18 F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico-pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG-PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into 'low' and 'high' diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19·2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3-year progression-free-survival (PFS) was 80% for patients with 'low BMU', 87% for 'high BMU', 69% for 'unifocal' and 51% for 'multifocal' lesions; median follow-up was 38 months. The presence of bone lesions, both uni- and multifocal, was associated with significantly inferior PFS (log rank P = 0·0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/metabolismo , Neoplasias Óseas/diagnóstico por imagen , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos/farmacocinética , Estudios Retrospectivos , Suecia/epidemiología , Resultado del Tratamiento , Adulto Joven

RESUMEN

In Hodgkin lymphoma (HL) bleomycin can induce pulmonary toxicity (BPT). BPT consists of respiratory tract symptoms during bleomycin-exposure and radiologic pulmonary lesions without concomitant infection. Older age, bleomycin dose, smoking history and the use of granulocyte-colony stimulating factor (G-CSF) have been suggested as possible risk factors for BPT. It is still debated whether BPT affects overall (OS) and progression-free survival (PFS). We investigated the incidence of BPT along with possible risk factors in 412 HL patients treated in 1990-2014. BPT occurred in 34 patients (8%) and was significantly associated with disseminated disease and B-symptoms. It was more frequent in elderly patients (p = .05) but not significantly correlated with a history of smoking. BPT occurred more often in patients receiving G-CSF (p = .03), particularly the poly-ethylenglycol-bound molecule. All significant risk correlations were limited to the age group >45 years. In the present cohort, BPT did not influence OS or PFS regardless of age.

Asunto(s)

Bleomicina/efectos adversos , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/epidemiología , Lesión Pulmonar/epidemiología , Lesión Pulmonar/etiología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/uso terapéutico , Dinamarca/epidemiología , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Historia del Siglo XX , Historia del Siglo XXI , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/historia , Humanos , Incidencia , Lesión Pulmonar/historia , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven

RESUMEN

We report a case presenting with recurrent episodes of severe hypothermia preceding the diagnosis of Hodgkin lymphoma. The episodes of hypothermia were accompanied by other symptoms of autonomic dysfunction, mainly hypotension, which could be caused by autonomic neuropathy as part of a paraneoplastic syndrome. In comparison with previous reports describing an association between the presence of hypothermia and an adverse outcome, the present patient has responded well to lymphoma-specific treatment and is currently in an ongoing complete remission. Due to the peculiar cyclic pattern of the hypothermic episodes presented in this case, we hypothesize whether intermittent release of disease-related chemo- and cytokines could be a plausible pathogenetic explanation.