RESUMEN
Clinical trials in chronic myeloid leukemia (CML) are usually carried out in specialized centers whereas primary care for patients (pts) with CML is mainly provided by local oncology practices. The aim of this study was to assess treatment practices in pts with CML in the setting of private oncology practices in Germany. We collected data of 819 pts with a confirmed diagnosis (dx) of CML in 2013 or later from 43 practices. At dx, 84.2% (n=690) and 9.4% (n=77) of pts were in chronic or accelerated phase, 0.7% (n=6) had a blast crisis. Molecular monitoring was provided by EUTOS certified laboratories in 87.7% of pts. Typical BCR::ABL1 transcripts were detected in 86.6% (n=709). Molecular response was assessed after 2.8, 6.0, 9.4 and 12.9 m (mean) after start of treatment. Of the pts with available data, 11.1% did not achieve early molecular response and at 18 m, 83.7% had at least a major molecular response. 288 (35.2%) of pts switched to 2nd line (2L) treatment after a mean of 21.0 months. Reasons for 2L treatment were side effects in 43.4% and suboptimal response or failure in 31.4% of pts. 106 pts went on to third line (3L) treatment. 36.8 % of pts switched to and 92.8 % of pts still on 3L treatment achieved BCR::ABL1IS ≤1% at 12 m. In conclusion, in Germany pts with CML are routinely monitored by qPCR and good responses are achieved in the majority. Treatment changes are mainly due to adverse events rather than suboptimal responses.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Humanos , Estudios Retrospectivos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Crisis Blástica , Alemania/epidemiología , Proteínas de Fusión bcr-abl/genética , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
PURPOSE: The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification. METHODS: In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper-pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification. RESULTS: Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients. CONCLUSIONS: Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria.
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Trastornos Mieloproliferativos , Neoplasias , Mielofibrosis Primaria , Trombocitemia Esencial , Humanos , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/terapia , Estudios Retrospectivos , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/epidemiología , Trastornos Mieloproliferativos/terapiaAsunto(s)
Enfermedad de Hodgkin/epidemiología , Progresión de la Enfermedad , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Recurrencia Local de Neoplasia , Evaluación del Resultado de la Atención al Paciente , Factores de Riesgo , Trasplante AutólogoRESUMEN
Depending on stage and risk factor profile, up to 95% of patients with Hodgkin lymphoma at first presentation reach complete remission after the initial standard treatment including radiotherapy, combination chemotherapy or combined modality therapy. Patients who relapse after first complete remission can achieve a second complete remission and long-term disease-free survival with salvage treatment including radiotherapy for localized relapse in previously nonirradiated areas, conventional salvage chemotherapy, or high-dose chemotherapy with stem cell transplantation. In general, risk-adapted treatment strategies are used in the treatment of patients with Hodgkin lymphoma. Adequate staging of newly diagnosed patients enables optimal treatment planning, which is of particular importance for finding a balance between treatment efficacy and toxicity. In this review, an overview is given of the current knowledge of clinical and biological risk factors and the role of imaging modalities during and after treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/fisiopatología , Humanos , Masculino , Radioterapia , Recurrencia , Inducción de Remisión , Factores de Riesgo , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
PURPOSE: High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy. PATIENTS AND METHODS: Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points. RESULTS: From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001). CONCLUSION: Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/cirugía , Humanos , Estimación de Kaplan-Meier , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Trasplante de Células Madre de Sangre Periférica , PronósticoRESUMEN
For older patients with early unfavorable or advanced stage Hodgkin lymphoma (HL) the prognosis is much worse than for younger HL patients. We thus developed a new regimen, BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone), to improve both tolerability and efficacy of treatment for older HL patients. Between 2004 and 2005, 65 patients with early unfavorable or advanced stage HL aged between 60 and 75 years were enrolled in this phase 2 trial. Treatment consisted of 6 to 8 cycles of BACOPP. Residual tumor masses were irradiated. Primary endpoints were feasibility as determined by adherence to protocol and overall response rate. Secondary endpoints included toxicity, freedom from treatment failure, and progression free and overall survival. For the final analysis 60 patients (92%) were eligible; 75% of treatment courses were administered according to protocol. World Health Organization grade 3/4 toxicities occurred in 52 patients. Fifty-one patients (85%) achieved complete remission, 2 (3%) partial remission, and 4 (7%) developed progressive disease. With a median observation time of 33 months, 18 patients died (30%), including 7 treatment-associated deaths. Three patients died before response assessment. Thus, the BACOPP regimen is active in older HL patients but is compromised by a high rate of toxic deaths. This trial was registered at www.clinicaltrials.gov as #NCT00284271.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Bleomicina/administración & dosificación , Ciclofosfamida , Progresión de la Enfermedad , Doxorrubicina/administración & dosificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Alemania , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Inducción de Remisión , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
PURPOSE: To determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkin's lymphoma (HL). PATIENTS AND METHODS: The prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs. RESULTS: PROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P < .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P < .001). CONCLUSION: Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.
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Anemia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Eritropoyetina/uso terapéutico , Hematínicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anemia/sangre , Anemia/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Método Doble Ciego , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Epoetina alfa , Transfusión de Eritrocitos , Eritropoyetina/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Fatiga/tratamiento farmacológico , Fatiga/etiología , Femenino , Alemania , Hematínicos/efectos adversos , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Prednisona/efectos adversos , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Proteínas Recombinantes , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos , Adulto JovenRESUMEN
To date, there is little information on the impact of more aggressive treatment regimen such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) on the fertility of male patients with Hodgkin lymphoma (HL). We evaluated the impact of BEACOPP regimen on fertility status in 38 male patients with advanced-stage HL enrolled into trials of the German Hodgkin Study Group (GHSG). Before treatment, 6 (23%) patients had normozoospermia and 20 (77%) patients had dysspermia. After treatment, 34 (89%) patients had azoospermia, 4 (11%) had other dysspermia, and no patients had normozoospermia. There was no difference in azoospermia rate between patients treated with BEACOPP baseline and those given BEACOPP escalated (93% vs 87%, respectively; P > .999). After treatment, most of patients (93%) had abnormal values of follicle-stimulating hormone, whereas the number of patients with abnormal levels of testosterone and luteinizing hormone was less pronounced-57% and 21%, respectively. In univariate analysis, none of the evaluated risk factors (ie, age, clinical stage, elevated erythrocyte sedimentation rate, B symptoms, large mediastinal mass, extranodal disease, and 3 or more lymph nodes) was statistically significant. Male patients with HL are at high risk of infertility after treatment with BEACOPP.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azoospermia/inducido químicamente , Fertilidad/efectos de los fármacos , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Bleomicina/efectos adversos , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Etopósido/efectos adversos , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Alemania , Humanos , Hormona Luteinizante/sangre , Masculino , Valor Predictivo de las Pruebas , Prednisona/efectos adversos , Procarbazina/efectos adversos , Pronóstico , Recuento de Espermatozoides , Testosterona/sangre , Vincristina/efectos adversosRESUMEN
PURPOSE: Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL patients registered in the German Hodgkin Study Group (GHSG) database, comparing patient characteristics and treatment outcome with cHL patients. PATIENTS AND METHODS: We analyzed retrospectively 8,298 HL patients treated within the GHSG trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL. RESULTS: Complete remission and unconfirmed complete remission after first-line treatment was achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced stages of LPHL compared with cHL, respectively. Tumor control (freedom from treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50 months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%, respectively (P = .0166). In LPHL patients, negative prognostic factors were advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia (P = .010) for FFTF. Age >or= 45 years (P = .0125), advanced stage (P = .0153), and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS. CONCLUSION: The better prognosis of LPHL as compared with cHL might allow different treatment strategies, particularly for early-stage LPHL patients.
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Enfermedad de Hodgkin/patología , Linfocitos/patología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Supervivencia sin Enfermedad , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate treatment outcome of patients with early-stage favorable Hodgkin's lymphoma (HL) who experience disease relapse after primary treatment with two cycles of chemotherapy followed by radiotherapy (RT). PATIENTS AND METHODS: Of 1,129 patients with early-stage favorable HL enrolled onto the HD7/HD10/HD13 trials of the German Hodgkin Study Group, 42 patients were identified with treatment failure, of whom eight had primary progressive disease, seven had early relapse (< or = 12 months), and 27 had late relapse (> 12 months). We analyzed this group of patients for risk factors, salvage therapy, and treatment outcome. RESULTS: The median age was 41 years (range, 19 to 72 years); 24 patients were male, 15 patients had outfield relapse, 13 patients infield relapse, and nine patients outfield and infield relapse. At relapse, 24 patients were treated with conventional salvage chemotherapy, 14 patients were treated with high-dose chemotherapy followed by autologous stem-cell transplantation, and four patients were treated with RT alone. At 36 months median follow-up, freedom from second treatment failure (FF2F) and overall survival (OS) were 52% and 67%, respectively. According to the prognostic score for relapsed HL (duration of first remission, clinical stage, and anemia at relapse), patients with two or three poor prognostic features had a significantly worse outcome compared with patients with none or one of these factors (P < .05 for FF2F and OS). CONCLUSION: Relapse after primary treatment with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine followed by RT is rare. In our analysis, results were influenced by a high treatment-related mortality rate. Additional studies are needed to define the optimal salvage therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Recurrencia Local de Neoplasia/terapia , Adolescente , Adulto , Anciano , Terapia Combinada , Progresión de la Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Terapia Recuperativa , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: The BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) chemotherapy regimen for the treatment of advanced Hodgkin's lymphoma has a superior outcome, but its toxicity (mainly haematotoxicity) is pronounced and highly variable. The present study was conducted to address the role of pharmacokinetics in individual toxicity. STUDY DESIGN: Three plasma samples and a 24-hour urine collection for day 1 of the first three cycles of chemotherapy were analysed in 30 patients, and the pharmacokinetic parameters of the respective drugs were estimated by population pharmacokinetic methods (nonlinear mixed-effects model [NONMEM] software). Demographic data, doses and durations of infusion were also recorded. The effect of these parameters on platelet counts was estimated by analysis of covariance using a general linear model. RESULTS: The pharmacokinetic parameters and respective covariates were similar to the published data. The body surface area, peak concentrations of etoposide, urinary recovery of dechloroethylcyclophosphamide (formed by cytochrome P450 [CYP] 3A4) relative to the cyclophosphamide dose and number of cycles had a significant effect on toxicity. These factors explained 37% of the interindividual variability in the change in platelet counts from day 1 to day 8 of each cycle. CONCLUSION: The results show that the individual pharmacokinetics of BEACOPP drugs are an important link between dosage and toxicity. Accordingly, individualisation of treatment based on pharmacokinetics may result in more uniform toxicity. Individualisation may also allow escalation of the mean dose, which is probably related to better efficacy. As a consequence of the present study, infusion rates should be standardised, and the potential of a dose reduction in the first cycle and of CYP3A4 phenotyping should be addressed in clinical studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Recuento de Plaquetas , Adolescente , Adulto , Análisis de Varianza , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Superficie Corporal , Ciclofosfamida/administración & dosificación , Ciclofosfamida/análogos & derivados , Ciclofosfamida/orina , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/metabolismo , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Persona de Mediana Edad , Fenotipo , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m(2)) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.
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Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Trasplante de Células Madre , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales de Origen Murino , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/cirugía , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Over the last decade diagnostic techniques such as immunophenotyping as well as cytogenetic and molecular profiling gave new insights into the pathogenesis of malignant lymphoma and helped to establish the WHO classification. The recognition of well-defined biological entities with distinct response and relapse patterns led to the development of more specific treatment strategies for individual lymphoma subtypes. New treatment modalities such as the monoclonal antibody rituximab have improved the results of first-line treatment of patients with certain B-cell lymphoma subtypes substantially. Furthermore, new prognostic factors were described for different lymphoma entities leading to further differentiation of treatment. As a consequence, the quality of relapse after first-line therapy has changed and treatment strategies for relapsed disease need to be redefined. This review summarises current salvage treatment options for common lymphoma subtypes taking into account variables which should be considered before an individual patient is treated. We focus on follicular lymphoma, diffuse large B-cell lymphoma and Hodgkin disease since these are most frequent and evidence-based salvage strategies are beginning to emerge.
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Linfoma/terapia , Terapia Recuperativa/métodos , Enfermedad de Hodgkin/terapia , Humanos , Linfoma Folicular/terapia , Linfoma de Células B Grandes Difuso/terapia , Radioinmunoterapia , Trasplante de Células Madre , Trasplante Autólogo , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
Hodgkin and Reed-Sternberg cells are derived from germinal center B cells. Amplification of identical rearranged and mutated immunoglobulin genes from different Hodgkin and Reed-Sternberg cells from the same patient also answered the question of the malignant nature because the clonality-the key criterion of malignancy-of Hodgkin and Reed-Sternberg cells was hereby shown. In addition, it could be demonstrated that Hodgkin and Reed-Sternberg cells do not only expand clonally within 1 affected lymph node, but also clonally disseminate in advanced-stage disease and relapse even after clinical complete remission. Recent publications demonstrate that a probably small subset of Hodgkin disease exists with T-cell derivation of the respective Hodgkin and Reed-Sternberg cells. The management of Hodgkin's disease is undergoing a paradigm shift as a result of very effective drug regimens that are capable of inducing high remission rates, the use of combined chemoradiotherapy with involved-field irradiation in early stages, the introduction of effective salvage chemotherapy of relapsed Hodgkin's disease with peripheral stem cell transplantation, a better understanding of prognostic factors, economic constraints, and a more sensitive realization of the magnitude of late treatment mortality.
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Enfermedad de Hodgkin , Terapia Combinada , Supervivencia sin Enfermedad , Reordenamiento Génico de Linfocito B/genética , Reordenamiento Génico de Linfocito B/inmunología , Centro Germinal/inmunología , Centro Germinal/patología , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Humanos , Mutación/inmunología , Pronóstico , Células de Reed-Sternberg/inmunología , Células de Reed-Sternberg/patología , Inducción de Remisión , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
PURPOSE: Several scores have described sex as a prognostic factor in patients with Hodgkin's lymphoma (HL). However, little is known how sex-specific factors influence treatment outcome. We systematically investigated sex differences with regard to pretreatment characteristics and therapy-related variables, and examined their influence on the outcome of HL patients. PATIENTS AND METHODS: This analysis comprises 4,626 HL patients of all prognostic risk groups who were enrolled onto the multicenter studies HD4 to HD9 of the German Hodgkin Study Group. At 5.5 years, 2,050 female and 2,576 male patients were analyzed. RESULTS: Male and female patients had similar prognostic factors. There was more acute chemotherapy-related hematotoxicity in women, especially more severe leucopenia (WHO grade 3/4, 69.9% female and 55.2% male; P < .0001). Importantly, this did not translate into more infections. Female patients had similar response rates but fewer relapses and deaths, leading to a significantly better freedom from treatment failure (FFTF; at 66 months, 81% female [95% CI, 79% to 82%] and 74% male [95% CI, 72% to 76%]). Severe leucopenia during chemotherapy was strongly associated with better FFTF, both for males and females. In addition, when only those patients who developed severe leucopenia within the first two cycles of chemotherapy were included, the factor maintained its protective role. CONCLUSION: The protective role of severe leucopenia suggests the testing of a more individualized therapy. In future trials, this therapy may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedad de Hodgkin/tratamiento farmacológico , Leucopenia/inducido químicamente , Recurrencia Local de Neoplasia/tratamiento farmacológico , Factores Sexuales , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Alemtuzumab , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/administración & dosificación , Resistencia a Antineoplásicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
PURPOSE: To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-rich classical Hodgkin's lymphoma (LRCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL). PATIENTS AND METHODS: From a total of 2,715 patients with biopsy-proven HL treated within the trials HD7 to HD12 of the German Hodgkin's Study Group, 100 patients (4%) with LRCHL, 145 patients (5%) with lymphocyte-predominant HL (LPHL), 1,688 patients (62%) with nodular sclerosis, 731 patients (27%) with mixed cellularity, and 23 patients (1%) with lymphocyte depletion were identified. Patients with LRCHL had a median age of 38 years (range, 16 to 74 years). RESULTS: Compared with other histologic subtypes, patients with LRCHL are, on average, older and usually present with early stages of disease (stage I, 34%; stage II, 46%). The median time of follow-up was 32.2 months (95% CI, 28.2 to 37.0 months). Complete and partial remission was achieved in 96 patients (96%) and four patients (4%), respectively, with LRCHL. The event-free and overall survival rates were 97% (95% CI, 93% [corrected] to 100% [corrected]) and 97% (95% CI, 93% [corrected] to 100% [corrected]), respectively, at 30 months. Only three patients died; all of the deaths were caused by treatment-related toxicities. CONCLUSION: LRCHL is a distinct subtype of CHL, with features of CHL and LPHL, and is a rare entity accounting for only 4% of HLs. LRCHL has a different pattern of clinical presentation and age and sex distribution than other CHLs. It is associated with an excellent prognosis if treated with current treatment regimens. When treating patients with LRCHL, great attention should be paid to avoid acute toxicities.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Anciano , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Femenino , Alemania , Enfermedad de Hodgkin/clasificación , Humanos , Linfocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dosificación Radioterapéutica , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The Sixth International Symposium on Hodgkin's disease was held in Cologne, Germany, between September 18 and 21, 2004, organized by the German Hodgkin Study Group (GHSG) and chaired by Volker Diehl. Since 1987 the international symposia were held at regular intervals in Cologne with the aim to facilitate international cooperation and to bring together new scientific and clinical results reached in the field of Hodgkin's disease. The expanding number of participants from about 300 attendees at the first symposium to almost 800 from 48 countries at the Sixth International Symposium indicates the increasing importance of this meeting. For the second time a patient seminar with more than 350 attendees has been organized. This sixth meeting was going to be unique, since the GHSG celebrated its 25th anniversary and honored Volker Diehl, the group's founder in recognition of his work during more than 25 yr. The symposium was held at the University of Cologne's main building, creating a special, scientific and familiar atmosphere. Throughout the symposia carried out by the GHSG, preclinical and clinical several topics have always been of basic interest and have provided a basis for discussion and scientific exchange.
Asunto(s)
Ensayos Clínicos como Asunto , Enfermedad de Hodgkin , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/fisiopatología , Enfermedad de Hodgkin/terapia , HumanosRESUMEN
Initial staging of Hodgkin's disease is crucial to determine the location and extent of disease, and is the hallmark for the choice of treatment. At present, the established radiological technique for staging Hodgkin's disease is computed tomography (CT). Modern multidetector row CT scanners allow fast imaging from the scull base to the groins during a single breath hold with a spatial resolution of approximately 1 mm. Both, nodal and extranodal involvement of Hodgkin's disease can be diagnosed with CT. Magnetic resonance (MR) imaging is another useful cross-sectional imaging modality for staging Hodgkin's disease. The development of fast MR imaging techniques has considerably reduced imaging time without compromising the quality of MR images. As a consequence, MR imaging is now considered to be as diagnostic as CT for staging Hodgkin's disease. The excellent soft-tissue contrast and the lack of exposure to ionizing radiation are the main advantages of MR imaging. For the detection of extranodal Hodgkin's disease, MR imaging is superior to assess involvement of the brain, the spinal cord and bone marrow; while CT allows excellent evaluation of lung disease. Common major problems in staging Hodgkin's disease are still the detection of nodal involvement in normal sized lymph nodes and residual tumor masses after therapy. In the future, newly developed lymphotropic contrast agents for MR imaging might be helpful to answer these questions.