Prolonged complete remission of myelodysplastic syndrome treated with danazol, retinoic acid and low-dose prednisone

Abstract

Myelodysplastic syndrome (MDS) is a diverse group of clonal hematologic neoplasms. Different medications have been tried in MDS; however, no effective treatment has been yet established. We report a patient with MDS who achieved a complete remission in response to combination therapy of danazol, retinoic acid, and prednisone. A 53-year-old female presented with pancytopenia, macrocytosis, and hypercellular bone marrow with erythroid hyperplasia and dysplasia and 10% ringed sideroblasts. Cytogenetic studies revealed the presence of two abnormal clones. She was diagnosed as having MDS-refractory anemia and was given blood transfusions to maintain blood cell counts at acceptable levels. At the same time, she was started on a combination of danazol (600 mg/day), retinoic acid (100 mg/day), and prednisone (10 mg every other day). Fourteen months later, the patient was in complete hematologic remission; she had normal peripheral blood count, and the blood smear showed normal morphology. Bone marrow studies revealed normal trilineage hematopoiesis. She was continued on the same combination treatment for 86 months, and she remained in complete clinical remission. Eighty-eight months from diagnosis, she relapsed with acute myeloid leukemia. This is the first reported case of MDS-RA that sustained a complete hematologic remission for a prolonged period in response to this combination treatment. This report indicates that restoration of normal hematopoiesis, prolongation of disease-free survival, and delay in the transformation to acute leukemia may be achieved by this combination of treatment in a subset of patients with MDS, especially refractory anemia with severe thrombocytopenia.

Dramatic remission of anemia after thymectomy in a patient of idiopathic myelofibrosis with thymoma

“…Danazol, a synthetic attenuated androgen, has been used widely for anemia in variety of disorders, including pure red cell aplasia, autoimmune hemolytic anemia, aplastic anemia, and IMF [9][10][11][12][13][14]. Cervantes et al [15] reported 30 IMF patients who took danazol for 20.5 months and 11 patients (37%) achieved complete remission (transfusion cessation with normal hemoglobin level).…”

Genomic Predictors Associated With Exceptional Response to Systemic Therapy in Advanced Pancreatic Cancer

“…10,11 One study evaluating distinct molecular subtypes in pancreatic cancer that included 178 patients from The Cancer Genome Atlas found only 2 patients with BAGE2 deletions, which showed no correlation with exceptional response or favorable outcomes. 12 Our study highlights the importance of searching for biomarkers of response to identify smaller subsets of patients who experience exceptional responses not observed in the broader population. For example, the original trials of EGFR inhibitors in lung adenocarcinoma with no biomarker selection showed only modest activity, but once EGFR was identified as a predictive biomarker in a subset of patients, the true activity of these drugs became apparent.…”

“…Although the patient might welcome such access, it could raise concerns among parents, caregivers, and guardians regarding the level of details visible to the patient. 12,13…”

“…10,11 Additionally, danazol has proven useful in immunological cytopenias; its androgenic features, which promote healthy hematopoiesis and decrease neoplastic cell clones, are thought to be responsible for its efficacy. [11][12][13] One study noted a 5-year overall survival rate of approximately 60% for patients with aplastic anemia treated with danazol. 14 There is, however, conflicting evidence that androgens may be helpful in MDS.…”

Danazol inhibits aromatase activity of endometriosis-derived stromal cells by a competitive mechanism

“…Danazol, the 2,3-isoxazol derivative of 17␣-ethynyl T, is a synthetic androgen and has been used for the treatment of endometriosis (8), mastopathy (9), myelodysplastic syndrome (10), and other diseases (11). Several pharmacological effects of danazol have been reported, including inhibition of gonadotropin release (12), competitive inhibition of steroidogenic enzymes (13), modulation of immunological function (14), and suppression of cell proliferation (15).…”