Complete remission of t(11;17) positive acute promyelocytic leukemia induced by all-trans retinoic acid and granulocyte colony-stimulating factor

The combined use of retinoic acid and chemotherapy has led to an important improvement of cure rates in acute promyelocytic leukemia. Retinoic acid fo rces terminal maturation of the malignant cells and this application repres ents the first generally accepted differentiation-base therapy in leukemia. Unfortunately, similar approaches have failed in other types of hematologi cal malignancies suggesting that the applicability is limited to this speci fic subgroup of patients. This has been endorsed by the notorious lack of r esponse in acute promyelocytic leukemia bearing the variant t(11;17) transl ocation. Based on the reported synergistic effects of retinoic acid and the hematopoietic growth factor granulocyte colony-stimulating factor (G-CSF), we studied maturation of t(11;17) positive leukemia cells using several co mbinations of retinoic acid and growth factors. In cultures with retinoic a cid or G-CSF the leukemic cells did not differentiate into mature granulocy tes, but striking granulocytic differentiation occurred with the combinatio n of both agents. At relapse, the patient was treated with retinoic acid an d G-CSF before reinduction chemotherapy. With retinoic acid and G-CSF treat ment alone, complete granulocytic maturation of the leukemic cells occurred in vivo, followed by a complete cytogenetical and hematological remission. Bone marrow and blood became negative in fluorescence in situ hybridizatio n analysis and semi-quantitative polymerase chain reaction showed a profoun d reduction of promyelocytic leukemia zinc finger-retinoic acid receptor-al pha fusion transcripts. This shows that t(11;17) positive leukemia cells ar e not intrinsically resistant to retinoic acid, provided that the proper co stimulus is administered. These observations may encourage the investigatio n of combinations of all-trans retinoic acid and hematopoietic growth facto rs in other types of leukemia. (C) 1999 by The American Society of Hematolo gy.