RESUMEN
We report the case of a 61-year-old Canadian male of Maltese descent investigated for unexplained polycythemia. Decreased p50 suggested the presence of a high oxygen affinity hemoglobin (Hb) variant. Molecular genetic testing demonstrated that he carries a novel missense mutation (HBB: c.258T>G), resulting in a PheâLeu substitution at position 85 of the ß chain. The novel Hb variant has been designated Hb Kennisis in recognition of where the proband resides. Two other missense mutations have been reported at this position [Hb Bryn Mawr or Hb Buenos Aires, ß85(F1)PheâSer (HBB: c.257T>C); Hb Grantham, ß85(F1)PheâCys; (HBB: c.257T>G)], both of which have increased oxygen affinity.
Asunto(s)
Hemoglobinas Anormales/genética , Mutación Missense , Oxígeno/metabolismo , Policitemia/genética , Globinas beta/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Hemoglobinas Anormales/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Policitemia/sangre , Policitemia/diagnóstico , Policitemia/fisiopatología , Unión Proteica , Globinas beta/metabolismoRESUMEN
The purpose of this study was to determine the recommended phase II dose of liposomal doxorubicin (Caelyx ; Doxil in the United States) in combination with cyclophosphamide and vincristine for previously treated patients with good performance status with relapsed or refractory small-cell lung cancer. Twenty-one eligible patients were enrolled between November 1999 and September 2001 and received liposomal doxorubicin 25-40 mg/m2, cyclophosphamide 750-1000 mg/m2, and vincristine 1.2 mg/m2 intravenously (I.V.) every 21 days. At doses of liposomal doxorubicin 40 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V., 1 of 6 patients had dose-limiting neutropenia and fever in cycle 2 and 2 of 6 developed grade 3 hand-foot syndrome during cycle 3. Therefore, the recommended phase II doses are liposomal doxorubicin 35 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V. every 21 days. Antitumor activity was seen at all dose levels. This combination is well tolerated and has evidence of antitumor activity. A phase II evaluation is ongoing.
