RESUMEN
A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).
Asunto(s)
Hematínicos , Síndromes Mielodisplásicos , Humanos , Lenalidomida/farmacología , Hematínicos/farmacología , Eritropoyesis , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Factor Estimulante de Colonias de Granulocitos/farmacología , Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Resultado del TratamientoAsunto(s)
Cromosomas Humanos Par 1 , Cromosomas Humanos Par 21 , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Proteínas de Unión al ADN/genética , Leucemia Mieloide/genética , Proteínas de Fusión Oncogénica/genética , Factores de Transcripción/genética , Transcripción Genética , Enfermedad Aguda , Resultado Fatal , Femenino , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/terapia , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación GenéticaRESUMEN
We report a prematurely born patient with a 68,XX karyotype. She presented with syndactyly of 2nd and 3rd toes, minor facial features, microcephaly, slender hands, bicuspid aortic valve, patent ductus arteriosus and hypotonia. Comparison with other reported cases is given.