RESUMEN
The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (≥1 g/m2 ) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotrexate over a 6 year period in the haematology department of the Lyon Sud University Hospital (Hospices Civils de Lyon, France) were included. Potential risk factors for delayed methotrexate elimination were tested in a generalized linear model by univariate analysis: patient age, gender, methotrexate dose, administration of PPI or ranitidine, and concomitant nephrotoxic drugs. A total of 412 cycles of methotrexate were administered to 179 patients. Proton-pump inhibitors were co-administered with methotrexate in 127 cycles and ranitidine in 192 cycles. Ninety-three cycles included no antacid drugs. A total of 918 plasma methotrexate assays were performed. Methotrexate concentrations were checked at 24 hours in 92% of cycles. Delayed methotrexate elimination was observed in 20.9% of cycles. A total of 63 cycles with delayed methotrexate elimination were only identified on plasma methotrexate measures at 72 hours: ie, plasma methotrexate was in the normal range at 24 and 48 hour post injection. Use of PPI/ranitidine or no antacid drugs did not increase risk of delayed elimination, with respectively delayed methotrexate elimination in 20.5%, 21.9%, and 19.4% of cycles (P = .89). Impaired baseline creatinine clearance showed significant association in univariate analysis. Fifteen patients showed grade 1 acute kidney injury, 1 grade 2, 2 grade 3, and none grade 4. For half of these cases, delayed methotrexate elimination was observed and the 2 grade 3 events appeared in patients treated with PPIs. This retrospective study suggests that there is no association between concomitant use of proton-pump inhibitors (pantoprazole and esomeprazole) or ranitidine and delayed methotrexate elimination.
Asunto(s)
Metotrexato/farmacocinética , Inhibidores de la Bomba de Protones/farmacología , Ranitidina/farmacología , Adulto , Anciano , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacología , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interacciones Farmacológicas , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/metabolismo , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/administración & dosificación , Ranitidina/administración & dosificación , Estudios Retrospectivos , Factores de TiempoAsunto(s)
Sistema Nervioso Central/patología , Leucemia Linfocítica Crónica de Células B/patología , Protocolos de Quimioterapia Combinada Antineoplásica , Encéfalo/patología , Humanos , Inmunohistoquímica , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Médula Espinal/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Less than 20% of patients with follicular lymphoma (FL) present with Ann Arbor Stage I or II disease at diagnosis. Numerous therapeutic options exist, however radiation therapy is considered the standard of care for early-stage disease based on single-institution or retrospective series. Our aim was to revisit the outcome of patients with localized FL in the rituximab era. PATIENTS AND METHODS: We analyzed the characteristics and outcomes of 145 early-stage FL patients, who were retrospectively divided into six groups according to their initial treatment: watchful waiting (WW), chemotherapy alone (CT), radiotherapy alone (RT), combined radiotherapy and chemotherapy (RT-CT), rituximab alone (Ri), and immunochemotherapy (Ri-CT). RESULTS: Of the 145 patients, 84 (57.9%) had stage I disease and 61 (42.1%) stage II. The complete response (CR) rate varied from 57% for the Ri group to 95% for the RT-CT group. Overall survival (OS) at 7.5 y of patients treated after 2000 was better than that of those treated prior to 2000. OS did not significantly differ from one treatment to another. In contrast, a significant difference was found for progression-free survival (PFS) at 7.5 y, which favored Ri-CT (60%) therapy versus the others (p=0.00135). CONCLUSION: Delayed therapy initiation was associated with a similar OS than that observed in patients receiving immediate intervention. The "watchful waiting" strategy may thus be proposed as first-line therapy, similar to stage III and IV FL patients with a low tumor burden. However, when treatment is required, immunochemotherapy appears to be the best option.
Asunto(s)
Linfoma Folicular/terapia , Anciano , Quimioradioterapia , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoterapia , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Linfoma Folicular/radioterapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Asparaginasa/administración & dosificación , Linfocitos T CD4-Positivos/metabolismo , Antígeno CD56/inmunología , Leucemia/tratamiento farmacológico , Metotrexato/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Trasplante de Células Madre/métodos , Trasplante Homólogo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/inmunología , Resultado del TratamientoRESUMEN
The role of rituximab retreatment in relapsed B-cell lymphoma is not well known. We undertook a single center retrospective cohort study to investigate the efficacy of retreatment with rituximab with or without chemotherapy in patients with relapsed and refractory B-cell lymphomas. We only included patients treated first-line and in first progression; 178 patients were included in the study, of whom 29% had diffuse large B-cell lymphoma (DLBCL) and 28% had follicular lymphoma (FL). The overall response rate for the first treatment was 81% and for the second treatment was 66%. The median progression-free survival (PFS) for all patients from diagnosis was 13.2 months and from relapse was 12.5 months (not statistically different). For DLBCL the median PFS from diagnosis was 9.6 months and from relapse was 8.4 months, and for FL the median PFS from diagnosis was 26.4 months and from relapse was 19.2 months (not statistically different). The 5-year overall survival was 57%. In a historical comparison with rituximab-naive patients, rituximab-retreated patients had a shorter time to initial relapse than control patients, but there was no difference between the two groups for PFS from relapse. In conclusion, retreatment with rituximab, with or without chemotherapy, yields a high overall response rate in patients with relapsed and refractory B-cell lymphomas. Relapse occurring after rituximab-containing therapy appears to be more aggressive than that occurring after chemotherapy alone. The outcome of retreatment, in terms of progression-free survival, is similar to that of primary treatment.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino , Estudios de Casos y Controles , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B/patología , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab , Resultado del TratamientoRESUMEN
We report the case of an immunocompetent 23-year-old Caucasian woman, with symptoms including rectal bleeding, tenesmus and epreint, 6 months after an anal sexual trauma. The rectal examination showed a hardened, inflammatory and painful anal margin, associated with stenosis of the anal canal, suggesting abscess. The neurological examination showed numbing of the chin. Pelvic MRI and CT scan confirmed a bulky posterior tissular pelvic mass more than 7 cm in diameter, infiltrating the rectum and the anal canal. Final diagnosis confirmed by biopsy performed during rectosigmoidoscopy was an Epstein-Barr Virus-Associated Burkitt's lymphoma. Chemotherapy resulted in rapid regression of the tumoral mass.
Asunto(s)
Linfoma de Burkitt , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/diagnóstico por imagen , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/patología , Femenino , Humanos , Inmunocompetencia , Imagen por Resonancia Magnética , Recto/patología , Sigmoidoscopía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphoma (MCL). METHODS: This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment. Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total body irradiation in 26 patients (77%). RESULTS: After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 10(6)/kg. Three months after transplantation, 24 patients (71%) were in CR, and 7 patients (21%) were in PR. At 3 years from the day of transplantation, the estimated overall survival was 87%. With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years. Rituximab treatment before harvest did not delay hematopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days. CONCLUSIONS: Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities.