RESUMEN
As we learn more about the etiology and cancer risks associated with Lynch syndrome (LS), the phenotypic spectrum of this condition and its genotype-phenotype correlations are being elucidated. We report a patient with past history of multiple cancers including colon and kidney cancer, and recently diagnosed with jejunal adenocarcinoma. The patient had microsatellite instability and immunohistochemistry (MSI/IHC) testing performed on his small bowel cancer in order to evaluate his risk for LS. The MSI/IHC results on his tumor tissue were reported as abnormal and subsequent blood draw revealed the presence of a germline MSH6 mismatch repair gene mutation. This case highlights the phenotypic variability of LS and complications it may present in evaluation for diagnosis and appropriate surveillance and management recommendations. To our knowledge, this is the first report of MSI/IHC being done on small bowel cancer to evaluate for this condition and subsequently confirmed via molecular analysis.
Asunto(s)
Adenocarcinoma/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias del Yeyuno/genética , Adenocarcinoma/patología , Anciano , Carcinoma de Células Renales/patología , Proteínas de Unión al ADN/genética , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Neoplasias del Yeyuno/patología , Neoplasias Renales/patología , Masculino , Inestabilidad de Microsatélites , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/genética , LinajeRESUMEN
Immunotherapy utilizing CAMPATH-1H for patients with chemotherapy-refractory chronic lymphocytic leukemia has yielded encouraging results with many reports of complete remission. Here we report the outcome of two patients with CD4-positive T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded rapidly to treatment and subsequently developed CD4 lymphopenia. One patient remained in complete remission after 14 weeks of treatment. Serial peripheral blood flow cytometry revealed that the CD52 antigen was present throughout treatment. The other patient who was initially CD52-positive, became CD52-negative after 6 weeks of treatment, and developed progressive symptoms of T cell prolymphocytic leukemia. Immunotherapy was stopped, chemotherapy proved futile, and the patient died. This change in phenotype from CD52-positive to -negative during CAMPATH-1H therapy points out a need to develop strategies for maintaining antigenic expression during monoclonal antibody therapy.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Antineoplásicos/farmacología , Antígenos CD/análisis , Antígenos de Neoplasias , Resistencia a Antineoplásicos , Glicoproteínas/análisis , Leucemia Prolinfocítica/patología , Anciano , Anciano de 80 o más Años , Alemtuzumab , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/administración & dosificación , Antígenos CD/efectos de los fármacos , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/patología , Antígeno CD52 , Resultado Fatal , Femenino , Glicoproteínas/efectos de los fármacos , Humanos , Inmunofenotipificación , Leucemia Prolinfocítica/tratamiento farmacológico , Leucemia Prolinfocítica/genética , Leucemia Prolinfocítica de Células T/tratamiento farmacológico , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/patología , Activación de Linfocitos/genética , Masculino , Persona de Mediana Edad , Fenotipo , Inducción de RemisiónRESUMEN
PURPOSE: We conducted a retrospective analysis to evaluate the safety and efficacy of Campath-1H, an anti-CD52 humanized monoclonal antibody, in previously treated T-prolymphocytic leukemia (T-PLL) patients in a compassionate-use program. PATIENTS AND METHODS: Seventy-six patients with T-PLL (including four chemotherapy-naive patients) received 3, 10, and 30 mg of Campath-1H on sequential days, followed by 30 mg three times weekly, as 2-hour intravenous infusions, for 4 to 12 weeks. RESULTS: Median patient age was 60 years (range, 35 to 84). Spleen liver, lymph node, and skin involvement were present in 64%, 40%, 54%, and 18% of patients, respectively. All tested patients had CD2, CD7, CD4, and/or CD8 positivity, whereas CD5 and CD3 were positive in 98% and 96% of tested patients, respectively. The objective response rate was 51% (95% confidence interval [CI], 40% to 63%), with a 39.5% complete response (CR) rate (95% CI, 28% to 51%). The median duration of CR was 8.7 months (range, 0.13+ to 44.4), and median time to progression was 4.5 months (range, 0.1 to 45.4) compared with 2.3 months (range, 0.2 to 28.1) after first-line chemotherapy. The median overall survival was 7.5 months (14.8 months for CR patients). The most common Campath-1H-related adverse events were acute reactions during or immediately after infusions. Fifteen infectious episodes occurred during treatment in 10 patients (13%), leading to treatment discontinuation in three. Eight patients experienced possibly related, late-onset infections. Severe thrombocytopenia and/or neutropenia occurred in six patients (8%), leading to treatment discontinuation in four. Two treatment-related deaths occurred. CONCLUSION: Campath-1H is an active drug in T-PLL patients for whom first-line therapy has failed. It has a favorable risk/benefit ratio and should be prospectively investigated in chemotherapy-naive patients.