RESUMEN
BACKGROUND: The current standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) is an anthracycline plus cytarabine. Both anthracyclines and cytarabine have been associated with the development of typhlitis, a serious adverse event characterized by inflammation of the bowel wall in patients with profound neutropenia, diagnosed by abdominal CT imaging and clinical symptoms. Given the paucity of available data, the aim of our study was to determine the incidence of typhlitis among AML patients receiving induction chemotherapy with idarubicin 12â¯mg/m2 (IDA), daunorubicin 60â¯mg/m2 (DNA60), or daunorubicin 90â¯mg/m2 (DNA90). METHODS: Adult patients with AML or MDS receiving either daunorubicin or idarubicin along with cytarabine as part of their induction regimen between January 1, 2009 and June 30, 2013 were included. A definition of typhlitis required CT confirmation of inflammation of the cecum only, defined as non-tumoral bowel wall thickening with or without pericolonic fat infiltration and fluid, according to CTCAE version 4.03 along with clinical symptoms. The primary endpoint was to determine the incidence of typhlitis among IDA, DNA60, and DNA90. Secondary endpoints included characterizing the variability of doses used in induction therapy and identifying any potential risk factors for the development of typhlitis. RESULTS: The overall incidence of typhlitis was 2.5%. When the definition was broadened to include the colitis, enteritis, or enterocolitis, the incidence increased. The inter-reliability ratings of the 2 radiologists' evaluations for each definition indicated substantial agreement (0.803 cecum, 0.834 ileocecal region only, and 0.752 enterocolitis). Neither the anthracycline chosen, nor the dose had a statistically significant impact on the incidence of typhlitis. In patients that developed typhlitis, all patients had clinical symptoms in addition to documented cecum inflammation on CT scan. All patients were managed conservatively with intravenous broad-spectrum antibiotics. CONCLUSION: To our knowledge, this is the first study to compare the incidence of typhlitis in adult patients receiving idarubicin or daunorubicin for the treatment of AML. The cumulative incidence of typhlitis was similar to the currently published literature, with the incidence being similar irrespective of the anthracycline chosen or dose. All patients were managed conservatively with broad-spectrum antibiotics. A more definitive definition of typhlitis may help clinicians identify affected patients sooner and choose appropriate targeted therapy.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Idarrubicina/administración & dosificación , Idarrubicina/efectos adversos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Tiflitis/inducido químicamente , Tiflitis/epidemiología , Adulto , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Daunorrubicina/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Idarrubicina/uso terapéutico , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tiflitis/tratamiento farmacológicoRESUMEN
Children and adolescents with Burkitt Lymphoma (BL) and combined central nervous system (CNS) and bone marrow involvement still have a poor prognosis with chemotherapy alone. We therefore investigated in children and adolescents with bone marrow (≥25% blasts) and/or CNS-positive Burkitt lymphoma the chemoimmunotherapy combination of rituximab (375 mg/m(2) ) and the standard chemotherapy arm of our previously reported French-American-British (FAB) Lymphome Malins de Burkitt (LMB) 96 trial. Central pathological and cytogenetic characterization was also performed. There were 40 evaluable patients with Burkitt histology (25 with leukaemia and 15 with CNS disease ± leukaemia). The chemoimmunotherapy regimen was well tolerated. The incidence of grade III/IV mucositis during induction cycles with combined chemotherapy and rituximab was 31% and 26%, respectively. The 3-year event-free survival (EFS)/overall survival (OS) was 90% (95% confidence interval [CI], 76-96%) in the entire cohort and 93% (95% CI, 61-99%) in patients with CNS disease. Based on the results of this trial, an international randomized study of FAB/LMB 96 chemotherapy ± rituximab for high-risk patients is currently under investigation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Adolescente , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Médula Ósea/patología , Linfoma de Burkitt/genética , Niño , Quimioterapia de Consolidación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Esquema de Medicación , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Genes myc , Humanos , Inmunoterapia , Infusiones Intravenosas , Estimación de Kaplan-Meier , Linfoma de Células B/genética , Quimioterapia de Mantención , Masculino , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Prednisona/administración & dosificación , Prednisona/efectos adversos , Inducción de Remisión , Rituximab , Tiflitis/inducido químicamente , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Typhlitis or neutropenic enterocolitis (NEC) is a life-threatening condition that occurs in neutropenic patients. Early recognition is crucial owing to high death rate. We present a case of a 54-year-old man, diagnosed with non-Hodgkin lymphoma who received a first cycle of rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), prednisolone (R-CHOP) chemotherapy 10 days prior presenting. He developed fever, mucositis, watery diarrhoea and right lower quadrant pain with rebound tenderness. He also had neutropenia, with an absolute neutrophil count of zero. CT abdomen confirmed the diagnosis of typhlitis, demonstrating characteristic terminal ileum, caecal and right-sided colon involvement. Moreover, stool PCR was also positive for toxigenic Clostridium difficile. Therefore, the patient was diagnosed with concomitant typhlitis and C difficile-associated diarrhoea (CDAD). He was empirically treated with intravenous cefepime, intravenous metronidazole and oral vancomycin. His symptoms resolved in 10 days. This case illustrated a successful medical treatment of typhlitis in concomitance with CDAD.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enterocolitis Seudomembranosa/inducido químicamente , Linfoma no Hodgkin/tratamiento farmacológico , Tiflitis/inducido químicamente , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Cefepima , Cefalosporinas/uso terapéutico , Clostridioides difficile , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Quimioterapia Combinada , Enterocolitis Seudomembranosa/diagnóstico , Enterocolitis Seudomembranosa/tratamiento farmacológico , Humanos , Masculino , Metronidazol/uso terapéutico , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prednisona/efectos adversos , Radiografía , Rituximab , Tiflitis/diagnóstico por imagen , Tiflitis/tratamiento farmacológico , Vancomicina/uso terapéutico , Vincristina/efectos adversosRESUMEN
BACKGROUND: Aberrant mucosal immune responses to antigens of the resident microbiota are a significant cause of inflammatory bowel diseases (IBD), as are genetic and environmental factors. Previous work from our laboratory demonstrated that Helicobacter bilis colonization of immunocompetent, defined microbiota mice induced antigen-specific immune responses to the resident microbiota, yet these mice failed to develop colitis, suggesting that the immunological provocation induced by H. bilis alone was insufficient to induce disease. AIM: The purpose of this study was to test the hypothesis that the introduction of a bacterial provocateur such as H. bilis enhances the host's susceptibility to IBD following an inflammatory event. METHODS: Defined microbiota (DM) mice colonized with H. bilis were administered low dose (1.5%) dextran sodium sulfate (DSS) in drinking water for 5 days followed by a 4-day restitution period. Severity of lesions was assessed grossly and microscopically. Differential expression of select mucosal genes and histopathologic lesions was characterized. RESULTS: Helicobacter bilis colonization increased the severity of intestinal inflammation induced by an inflammatory trigger in the form of low-dose DSS. An analysis of the molecular and cellular mechanisms associated with H. bilis colonization revealed significant increases in expression of mucosal genes associated with lymphocyte activation and inflammatory cell chemotaxis as well as increased infiltration of mucosal macrophages and T cells in mice colonized with H. bilis prior to DSS treatment versus DSS treatment alone. CONCLUSIONS: These results indicate that prior colonization with H. bilis heightens the host's sensitivity to enteric inflammation by altering mucosal homeostasis and initiating immune cell activation and migration.
Asunto(s)
Colitis/inducido químicamente , Colitis/fisiopatología , Susceptibilidad a Enfermedades/fisiopatología , Infecciones por Helicobacter/complicaciones , Helicobacter/fisiología , Tiflitis/inducido químicamente , Tiflitis/fisiopatología , Animales , Movimiento Celular/fisiología , Colitis/patología , Colon/patología , Colon/fisiopatología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Helicobacter/patogenicidad , Infecciones por Helicobacter/fisiopatología , Homeostasis/fisiología , Macrófagos/patología , Masculino , Ratones , Índice de Severidad de la Enfermedad , Linfocitos T/patología , Tiflitis/patologíaRESUMEN
A rare case of acute typhlitis is reported. The patient had undergone chemotherapy for a breast cancer. Clinical and diagnostic tools as well as general and topical care are examined.
Asunto(s)
Antineoplásicos/efectos adversos , Hidrocarburos Aromáticos con Puentes/efectos adversos , Taxoides/efectos adversos , Tiflitis/inducido químicamente , Adulto , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Carcinoma Ductal/tratamiento farmacológico , Femenino , Humanos , Reoperación , Taxoides/administración & dosificación , Resultado del Tratamiento , Tiflitis/diagnóstico , Tiflitis/cirugíaRESUMEN
Pemetrexed is U.S. Food and Drug Administration-approved as a second line, single-agent treatment of recurrent metastatic non-small cell lung cancer. Gastrointestinal side effects, including stomatitis, diarrhea, and vomiting are reported to be less than 1% and rarely severe. In the premetrexed clinical trial database of 1327 patients, various types of colitis were reported by a total of nine patients (0.6%). Typhilitis is a gastrointestinal complication of chemotherapy, which presents as fever and abdominal pain. The diagnosis is supported by the findings of bowel wall thickening on computed tomographic imaging. Typhilitis is usually seen in the setting of severe chemotherapy-induced neutropenia for acute leukemia. Nevertheless, it is increasingly recognized as a complication of therapy in solid tumors. We present the first documented case of typhilitis after treatment with pemetrexed and successful therapy with supportive treatment.
Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Glutamatos/efectos adversos , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Tiflitis/inducido químicamente , Adenocarcinoma Bronquioloalveolar/complicaciones , Adenocarcinoma Bronquioloalveolar/diagnóstico por imagen , Adenocarcinoma Bronquioloalveolar/tratamiento farmacológico , Adulto , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Femenino , Guanina/efectos adversos , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Pemetrexed , Timidilato Sintasa/antagonistas & inhibidores , Tomografía Computarizada por Rayos X , Tiflitis/diagnóstico por imagenRESUMEN
INTRODUCTION: Typhlitis is a rare condition, characterized by necrotizing inflammation of the colon. It occurs mainly in neutropenic patients receiving chemotherapy for leukemia. EXEGESIS: We report the case of a 64-year-old woman with T-cell lymphocytic leukaemia, who exhibited asymptomatic reactivation of cytomegalovirus infection and developed subsequently typhlitis. CONCLUSION: The pathological mechanisms of typhlitis remain unclear in neutropenic patients. The role of cytotoxic drugs as well as both bacterial overgrowth and translocation has been postulated. In our patient, asymptomatic reactivation of cytomegalovirus infection may have increased chemotherapeutic-agents-digestive toxicity.