RESUMEN
Patients undergoing treatment for acute lymphoblastic leukaemia (ALL) are at risk of coagulopathy, especially thromboembolism. We conducted a survey on practices in the assessment and management of coagulopathy during the new ALLTogether protocol in 29 (17 paediatric, 12 adult) Nordic and Baltic cancer centres. While 92% of adult centres used thromboprophylaxis with low-molecular-weight heparin, no paediatric centre did. Almost all providers performed baseline coagulation studies, but only 59% continued the assessment. Fibrinogen replacement was conducted in 59%, and antithrombin replacement in 28% of the centres. The survey highlights the need for guidelines in the management of coagulopathy during ALL therapy.
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Trastornos de la Coagulación Sanguínea , Leucemia-Linfoma Linfoblástico de Células Precursoras , Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Antitrombinas/efectos adversos , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Niño , Fibrinógeno/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tromboembolia Venosa/inducido químicamente , Tromboembolia Venosa/prevención & control , Adulto JovenRESUMEN
Considering treatment changes and an improved prognosis of non-Hodgkin lymphoma (NHL) over time, knowledge regarding long-term health outcomes, including late effects of treatment, has become increasingly important. We report on time trends of second primary malignancies (SPMs) in Swedish NHL patients, encompassing the years before as well as after the introduction of anti-CD20 antibody therapy. We identified NHL patients in the Swedish Cancer Register 1993 to 2014 and matched comparators from the Swedish Total Population Register. The matched cohort was followed through 2017. By linking to the Swedish Lymphoma Register, subcohort analyses by NHL subtype were performed. Flexible parametric survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of SPM among patients and comparators. Among 32 100 NHL patients, 3619 solid tumors and 217 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) cases were observed, corresponding to a 40% higher rate of solid tumors (HRsolid tumors = 1.4; 95% CI, 1.4-1.5) and a 5-fold higher rate of MDS/AML (HRMDS/AML = 5.2; 95% CI, 4.4-6.2) than for comparators. Overall, the observed excess risks for solid tumors or MDS/AML remained stable over the study period, except for follicular lymphoma, where the excess rate of MDS/AML attenuated with time (P for trend = .012). We conclude that NHL survivors have an increased risk of both solid tumors and hematologic malignancies, in particular MDS/AML. Stable excess risks over time indicate that contemporary treatment standards are not associated with modified SPM risk. Encouragingly, decreasing rates of MDS/AML were noted among patients with follicular lymphoma, possibly due to the increasing use of nonchemotherapy-based treatments.
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Leucemia Mieloide Aguda , Linfoma Folicular , Linfoma no Hodgkin , Síndromes Mielodisplásicos , Neoplasias Primarias Secundarias , Humanos , Incidencia , Leucemia Mieloide Aguda/etiología , Linfoma Folicular/epidemiología , Síndromes Mielodisplásicos/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Suecia/epidemiologíaRESUMEN
PURPOSE: Osteonecrosis is a burdensome treatment-related toxicity that is mostly diagnosed during or soon after 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy for acute lymphoblastic leukemia (ALL), possibly indicating a pathogenic role of these drugs. METHODS: We prospectively registered symptomatic osteonecrosis during treatment of 1234 patients aged 1.0-45.9 years treated according to the Nordic Society of Hematology and Oncology (NOPHO) ALL2008 protocol. MTX/6MP metabolites were measured as part of the NOPHO ALL2008 maintenance therapy study. RESULTS: After a median follow-up of 5.6 years [interquartile range (IQR) 3.6-7.5], 68 patients had been diagnosed with symptomatic osteonecrosis. The cumulative incidence was 2.7% [95% confidence interval (CI) 1.6-3.8%] for patients aged < 10 years, 14.9% (95% CI 9.7-20.2%) for patients aged 10.0-17.9 years, and 14.4% (95% CI 8.0-20.8%) for patients aged ≥ 18 years. The median time from diagnosis of ALL to diagnosis of osteonecrosis in these age groups was 1.0 year (IQR 0.7-2.0), 2.0 years (IQR 1.1-2.4), and 2.2 years (IQR 1.8-2.8), respectively (p = 0.001). With 17,854 blood samples available for MTX and 6MP metabolite analysis, neither erythrocyte levels of 6-thioguanine (TG) nucleotides (p > 0.99), methylated 6MP metabolites (p = 0.37), MTX polyglutamates (p = 0.98) nor DNA-TG (p = 0.53) were significantly associated with the hazard of osteonecrosis in Cox models stratified by the three age groups and adjusted for sex. CONCLUSION: Maintenance therapy intensity determined by 6MP and MTX metabolites was not associated with the risk of developing osteonecrosis in the NOPHO ALL2008 cohort.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mercaptopurina/efectos adversos , Metotrexato/efectos adversos , Osteonecrosis/inducido químicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Niño , Preescolar , Aductos de ADN/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Humanos , Lactante , Masculino , Mercaptopurina/administración & dosificación , Mercaptopurina/farmacocinética , Metotrexato/administración & dosificación , Metotrexato/análogos & derivados , Metotrexato/metabolismo , Metotrexato/farmacocinética , Persona de Mediana Edad , Ácido Poliglutámico/análogos & derivados , Ácido Poliglutámico/metabolismo , Ácido Poliglutámico/farmacocinética , Estudios Prospectivos , Tioguanina/metabolismo , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias del Mediastino/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/epidemiología , Masculino , Neoplasias del Mediastino/epidemiología , Persona de Mediana Edad , Análisis de Supervivencia , Suecia/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
Patients with high-risk aggressive B-cell lymphoma exhibit poor survival after R-CHOP. More intensive regimens yield higher rates of remission but also of complication. We investigated all 401 patients < 70 years with high-risk (age-adjusted [aa] international prognostic index [IPI] ≥2, extranodal, or bulky) aggressive B-cell lymphoma hospitalized at Karolinska for urgent start of immunochemotherapy (129 R-Hyper-CVAD; 261 R-CHOP/R-CHOEP). Patients showed IPI 3-5 (70%), WHO PS ≥2 (49%), bulky disease (70%), extranodal (75%) and CNS (8%) involvement. Five-year overall/progression-free survival (OS/PFS) was better in patients who started R-Hyper-CVAD (84%/77%) compared with R-CHOP/R-CHOEP (66%/55%). Differences were independent in multivariable analysis, seen in all patient categories, and accentuated in extreme high-risk disease: R-Hyper-CVAD vs. R-CHOP/R-CHOEP showed 5-year PFS 69% vs.40% in aaIPI 3 and 88% vs. 38% in CNS involvement. For validation, survival was compared between the two Karolinska sites and calendar periods. Survival was superior 2006-2010 at the site that introduced R-Hyper-CVAD/R-MA 2006, identical at both sites 2011-2017 after the other site adopted R-Hyper-CVAD/R-MA 2011, and excellent 2018-2020 when R-Hyper-CVAD/R-MA use increased to 75% of patients. Despite considerable toxicity, also patients aged 61-69 years showed better survival with R-Hyper-CVAD/R-MA. This is the largest single-centre series of patients treated with R-Hyper-CVAD/R-MA, showing favourable outcome in high-risk aggressive B-cell lymphoma.
RESUMEN
OBJECTIVES: As new, effective therapies emerge for acute lymphoblastic leukaemia (ALL), the results of clinical trials need to relate to standard of care. METHODS: We used the population-based Swedish ALL Registry to evaluate characteristics, treatment and long-term outcome in 933 patients with diagnosis between 1997 and 2015. RESULTS: The median age was 53 years. The frequency of Philadelphia (Ph)-positive leukaemia was 34% of examined B-ALL with a peak incidence at 50-59 years. Five-year overall survival (OS) improved between 1997-2006 and 2007-2015; in patients 18-45 years from 50% (95% CI 43-57) to 65% (95% CI 58-72), 46-65 years from 25% (95% CI 18-32) to 46% (95% CI 37-55) and >65 years from 7% (95% CI 2.6-11) to 11% (95% CI 5.9-16) (P < 0.05). Men with Ph-neg B-ALL 46-65 years had inferior OS compared with women (P < 0.01). Standardised mortality ratio was 5.7 (95% CI 5.0-6.3) for patients who survived 5 years from diagnosis. In multivariable analysis, Ph-positive disease was not associated with impaired prognosis but with lower risk of death in 2007-2015. CONCLUSIONS: In a population-based cohort, OS has improved in adult ALL, especially for Ph-positive disease but for middle-aged men with Ph-negative B-ALL outcome was poor. Cure without late toxicity or relapse is still desired.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Vigilancia en Salud Pública , Sistema de Registros , Inducción de Remisión , Análisis de Supervivencia , Suecia/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
The treatment of choice in steroid-resistant immune thrombocytopenia is still controversial due to the recent advent of new drugs (anti-CD20 antibodies and thrombopoietin mimetics) that have encouraged a generalized tendency to delay splenectomy. Consequently, it is extremely importance to define the efficacy and safety of splenectomy in the long term. We retrospectively analyzed the data of 233 patients affected by immune thrombocytopenia who underwent splenectomy between 1959 and 2001 in 6 European hematologic institutions and who have now a minimum follow up of ten years from surgery. Of the 233 patients, 180 (77%) achieved a complete response and 26 (11%) a response. Sixty-eight of 206 (33%) responsive patients relapsed, mostly (75%) within four years from first response. In 92 patients (39.5%), further treatment was required after splenectomy that was effective in 76 cases (83%). In 138 patients (59%), response was maintained free of any treatment at last contact. No significant association between baseline characteristics and likelihood of stable response was found. Overall, 73 (31%) and 58 (25%) patients experienced at least one infectious or hemorrhagic complication, which was fatal in 2 and 3 patients, respectively. A stable response to splenectomy was associated with a lower rate of infections (P=0.004) and hemorrhages (P<0.0001). Thrombosis developed in 18 patients (8%) and was fatal in 4. Splenectomy achieved a long-term stable response in approximately 60% of cases. Complications mainly affected non-responding patients and were fatal in a minority.
Asunto(s)
Púrpura Trombocitopénica Idiopática/cirugía , Esplenectomía , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Pronóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To determine whether men and women with rheumatoid arthritis are prescribed anti-tumour necrosis factor (anti-TNF) treatment at different levels of disease activity. METHODS: Data from the Swedish national biologics registry ARTIS were used to analyse characteristics of patients' disease at the start of the first anti-TNF treatment. Means for men and women were compared using t-tests, and non-normally distributed covariates were compared using the Wilcoxon rank-sum test. Linear regression models, adjusted for age and calendar year, were used to investigate the association between sex and each disease activity measurement. RESULTS: Women were younger and had longer disease duration at treatment start than men. Tender joint count, erythrocyte sedimentation rate, patient's global assessment, patient-reported pain and health assessment questionnaire scores were significantly higher in women, whereas men had a higher level of C-reactive protein (p<0.05 for all comparisons). Swollen joint count and physician's global assessment did not differ by sex. CONCLUSIONS: For women with rheumatoid arthritis, treatment with anti-TNF therapy was initiated at a higher level of subjective disease activity than for men, but at the same level of physician-reported disease activity. These data imply that patients' subjectively experienced disease activity may be discounted in the treatment decision.