RESUMEN
BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/prevención & control , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/administración & dosificación , Lesión Renal Aguda/inducido químicamente , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/secundario , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Inyecciones Espinales , Linfoma de Células B Grandes Difuso/patología , Masculino , Metotrexato/efectos adversos , Persona de Mediana Edad , Prednisona/administración & dosificación , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Rituximab , Tasa de Supervivencia , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: The usefulness of positron emission tomography with computed tomography (PET-CT) in the surveillance of patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission after primary therapy is not well studied. METHODS: We performed a retrospective review of our database between 2002 and 2009 for patients with de novo DLBCL who underwent surveillance PET-CT after achieving complete metabolic response (CMR) following primary therapy. RESULTS: Four-hundred and fifty scans were performed in 116 patients, with a median follow-up of 53 (range 8-133) months from completion of therapy. Thirteen patients (11%) relapsed: seven were suspected clinically and six were subclinical (all within first 18 months). The positive predictive value in patients with international prognostic index (IPI) <3 was 56% compared with 80% in patients with IPI ≥3. Including indeterminate scans, PET-CT retained high sensitivity 95% and specificity 97% for relapse. CONCLUSION: Positron emission tomography with computed tomography is not useful in patients for the majority of patients with diffuse large B-cell lymphoma in CMR after primary therapy, with the possible exception of patients with baseline IPI ≥3 in the 18 months following completion of primary therapy. This issue could be addressed by a prospective clinical trial.
Asunto(s)
Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Monitoreo Fisiológico/métodos , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/estadística & datos numéricos , Imagen Multimodal/estadística & datos numéricos , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD20/inmunología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Terapia Recuperativa , Anciano , Anticuerpos Monoclonales Humanizados , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Transfusión de Eritrocitos , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Linfocitosis/tratamiento farmacológico , Linfocitosis/inmunología , Masculino , Persona de Mediana Edad , Terapia Recuperativa/métodosRESUMEN
Fludarabine combination chemotherapy achieves high response rates in chronic lymphocytic leukemia (CLL) and indolent lymphoma. The aim of this study was to investigate the incidence and characteristics of treatment-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) after treatment with fludarabine in combination for lymphoproliferative disorders and identify risk factors for its development. In all, 176 patients treated with fludarabine combination were followed for a median of 41 months (range 6-125 months). In all, 19 cases of t-MDS/AML have been identified for an overall rate of 10.8%. Median overall survival post-t-MDS/AML diagnosis was 11 months. Patients developing t-MDS/AML included 11/54 with follicular lymphoma (FL) (crude rate 20.4%), 5/82 with CLL (6.1%) and 3/24 with Waldenstrom macroglobulinemia or marginal zone lymphoma (12.5%). Most patients had other cytotoxic treatments (median 4, range 0-7) but three with FL had fludarabine combination as their only line of treatment. Of the eleven patients (6.3%) who received mitoxantrone with their first fludarabine combination, four (36.4%) developed t-MDS/AML (P=0.007). There was a trend toward prior cytotoxic therapy increasing the risk for t-MDS/AML (P=0.067). Fludarabine combination chemotherapy is associated with a moderate risk of t-MDS/AML particularly when combined with mitoxantrone. This complication should be considered when evaluating the potential benefit of this treatment in lymphoproliferative disorders.
Asunto(s)
Antineoplásicos/efectos adversos , Leucemia Mieloide Aguda/inducido químicamente , Síndromes Mielodisplásicos/inducido químicamente , Neoplasias Primarias Secundarias/inducido químicamente , Vidarabina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Vidarabina/efectos adversosRESUMEN
There is a major evolution in progress in the first-line therapy of chronic lymphocytic leukaemia. Several recent, large, clinical trials have documented superior outcomes with fludarabine-based therapy compared with treatment with alkylating agents. Monoclonal antibodies, especially rituximab, are establishing an important role for targeted treatment. It is expected that chemoimmunotherapy will become the preferred treatment for many patients in the near future. Specific challenges remain to be answered, however, especially the optimal treatment for the elderly, patients with autoimmune haemolysis and those with P53 deletions and mutations.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Humanos , Vidarabina/análogos & derivados , Vidarabina/uso terapéuticoRESUMEN
Fludarabine exposure leads to impaired peripheral blood stem cell (PBSC) mobilization in indolent lymphoproliferative disorders (LPD). We previously reported that only 34% of fludarabine-exposed patients mobilized successfully using granulocyte-colony stimulating factor (G-CSF; median 10 microg/kg/day) with or without chemotherapy, with unpredictable kinetics and moderate infectious morbidity. Stem cell factor (SCF) plus high-dose twice daily (b.d.) G-CSF may improve mobilization in these patients. SCF 20 microg/kg/day subcutaneously was given from day 1, G-CSF 12 microg/kg b.d. subcutaneously from day 4, apheresis commenced from day 6. Previous study patients served as historical controls. Thirty five patients with indolent LPD were enrolled, median age was 54 years (range 31-66), 66% male, median cumulative prior fludarabine dose was 660 (405-900) mg. Overall, 22 patients (63%) collected >or= 2.0 x 10(6)/kg PBSC (success), compared to 34% controls (odds ratio (OR) 3.2; 95% confidence interval (CI) (1.2, 9.3); P=0.021). Median CD34(+) yield overall was 2.3 x 10(6)/kg (0.53-8.97) from median four (2-6) aphereses. Study patients >or= 50 years mobilized successfully more frequently than controls (58 versus 17%; P=0.0065). Adjusting for age, successful mobilization remained significantly higher in the current study (OR 4.2; 95% CI (1.4, 14.0); P=0.008). SCF/high-dose b.d. G-CSF improves PBSC mobilization efficacy after fludarabine exposure, over mobilization using G-CSF as the mobilizing cytokine. This combined growth factor strategy is a preferred mobilization method for fludarabine-exposed patients.