RESUMEN
A 59-year-old woman was diagnosed with essential thrombocythemia in 1988 and had been treated with hydroxyurea, mitobronitol, busulfan, and ranimustine, in that order. Hepatosplenomegaly, low-grade fever, and body weight loss manifested, and a few blasts were noted in the peripheral blood studied in March 2002. A biopsied specimen of the bone marrow showed myelofibrosis but not a leukemia in August 2004. An abnormal karyotype with der(1; 13) appeared for the first time. She was treated with low-dose prednisolone. In January 2005, she experienced left hip joint pain, and magnetic resonance scanning showed a tumoral lesion in the femoral head. Histological diagnosis of the biopsied mass revealed that it was a granulocytic sarcoma, and radiotherapy was performed. In April 2005, bone scintigraphy showed multiple lesions. She became febrile and red blood cell transfusion-dependent with hepatosplenomegaly and a small number of circulating blasts. Intravenous cytarabine (low dose) and etoposide relieved the fever and hepatosplenomegaly; however, she developed a pathologic fracture of the right humerus. An additional karyotypic abnormality (7q22 deletion) was noted. She subsequently died of infection. Granulocytic sarcoma is very rare in essential thrombocythemia, and this patient may be the first reported case of essential thrombocythemia that developed multiple lesions and a pathologic fracture without transformation to overt leukemia.
Asunto(s)
Neoplasias Femorales , Mielofibrosis Primaria , Sarcoma Mieloide , Trombocitemia Esencial/complicaciones , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Transfusión Sanguínea , Deleción Cromosómica , Cromosomas Humanos Par 7 , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Resultado Fatal , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología , Fracturas del Fémur/genética , Fracturas del Fémur/patología , Fracturas del Fémur/terapia , Neoplasias Femorales/diagnóstico por imagen , Neoplasias Femorales/etiología , Neoplasias Femorales/genética , Neoplasias Femorales/patología , Neoplasias Femorales/terapia , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Persona de Mediana Edad , Mitobronitol/administración & dosificación , Mitobronitol/efectos adversos , Metástasis de la Neoplasia , Compuestos de Nitrosourea/administración & dosificación , Compuestos de Nitrosourea/efectos adversos , Mielofibrosis Primaria/diagnóstico por imagen , Mielofibrosis Primaria/etiología , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/patología , Mielofibrosis Primaria/terapia , Radiografía , Sarcoma Mieloide/diagnóstico por imagen , Sarcoma Mieloide/genética , Sarcoma Mieloide/patología , Sarcoma Mieloide/terapia , Trombocitemia Esencial/tratamiento farmacológico , Trombocitemia Esencial/patologíaRESUMEN
In a prospective, randomized trial the effectiveness of dibromomannitol (DBM), a brominated sugar alcohol derivative, was compared to busulfan in previously untreated patients. One hundred thirty-one patients were evaluated for response and survival. The effective dose of DBM was 4 mg/kg. The persistence of sensitivity to either DBM or busulfan was shown in a quantified fashion. Despite initial reports of the alleged unique effectiveness of DBM in treating chronic myeloid leukemia (CML), this study did not disclose any advantage of DBM over busulfan. Multivariate analysis investigating the importance of prognostic factors in CML indicated that age, sex, splenomegaly, and initial platelet count were important for predicting survival. Determination of such factors in CML are valuable in deciding those patients who could benefit from alternative forms of therapy. It also insures that study results are related to treatment rather than selection of patients with favorable or unfavorable prognostic factors.
Asunto(s)
Busulfano/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Manitol/análogos & derivados , Mitobronitol/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Busulfano/efectos adversos , Niño , Preescolar , Ensayos Clínicos como Asunto , Femenino , Humanos , Recuento de Leucocitos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Mitobronitol/efectos adversos , Pronóstico , Estudios Prospectivos , Distribución Aleatoria , Trombocitopenia/inducido químicamenteAsunto(s)
Manitol/análogos & derivados , Mitobronitol/efectos adversos , Policitemia Vera/tratamiento farmacológico , Alquilantes/administración & dosificación , Alquilantes/efectos adversos , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Pancitopenia/inducido químicamenteAsunto(s)
Antineoplásicos/efectos adversos , Oftalmopatías/inducido químicamente , Corticoesteroides/efectos adversos , Busulfano/efectos adversos , Quimioterapia Combinada , Antagonistas de Estrógenos/efectos adversos , Estrógenos/efectos adversos , Fluorouracilo/efectos adversos , Reacción Injerto-Huésped , Humanos , Mitobronitol/efectos adversos , Alcaloides de la Vinca/efectos adversosRESUMEN
Three hexitol derivatives, dibromomannitol (DBM), dibromodulcitol (DBD), and dianhydrogalactitol (DAG), originally investigated in Hungary, have been evaluated as anticancer agents in the United States. Their principal mechanism of action is attributed to alkylation via actual or derived epoxide groups. Their preclinical spectrum includes activity against murine leukemias and against the murine ependymoblastoma, which is particularly noteworthy for DAG. Dibromomannitol trials were targeted to chronic myelogenous leukemia but no advantage over busulfan therapy was demonstrable. Dibromodulcitol and DAG were sequentially evaluated for their usefulness against a wide variety of tumors. The activity of DBD against breast cancer has stimulated several continuing trials in this disease. On the other hand, DAG was disappointing in breast cancer and in several other malignancies, but some activity has been noted against lung cancer. Both DBD and DAG are being investigated for possible usefulness in the management of patients with intracranial neoplasms. The present clinical experience does not allow firm judgment on the advantage of one analogue over another. Such comparative analysis does point out the desirable direction of future studies as well as the limitations of current preclinical systems for the selection of analogues.