Revisiting accessible therapies for the management of Myelodysplastic Syndromes: A retrospective analysis of danazole, nandrolone or both. Free

“Revisiting accessible therapies for the management of myelodysplastic syndromes: a retrospective analysis of danazole, nandrolone or both” Introduction:

Androgen therapy has been explored as a potential disease-modifying strategy to improve hematologic parameters and reduce transfusion requirements in selected patients with myelodysplastic syndromes (MDS) particularly those with very low, low or intermediate risk. However, real-world data on hematologic response and transfusion independence in this population remain limited.

Methods:

We conducted a retrospective observational study including patients with MDS and treated with androgens (danazol, nandrolone, or both) between 2016 and 2025. Descriptive statistics were used to summarize clinical characteristics and response outcomes. Hematological responses were evaluated using the 2023 International Working Group criteria. Time to first response was calculated from treatment initiation to the first documented hematologic improvement. Kaplan Meier estimates were used to assess overall survival (OS). The cumulative incidence of hematological improvement (HI) considering death as a competing risk was estimated through the cumulative incidence function. Multivariable Fine-Gray regression was used to identify predictors associated with HI.

Results:

A total of 31 patients were analyzed, with a median age of 71 years (range 26–86). 61.3% of patients were male. The median hemoglobin at diagnosis was 8 g/dL (range 2.9–14.2), median platelet count was 20,900/mm³ (range 20–405,000), and median absolute neutrophil count (ANC) was 1,040/mm³ (range 0–45,871). The median number of monthly red blood cell transfusions prior to treatment initiation was 1 (range 0–5). Median duration of treatment was 168 days (range 15-1274). According to the IPSS-R, 35.5% were classified as Low, 45.2% as Intermediate, and 19.4% as High risk. The most frequent initial treatment was danazol in 58.1% of cases, followed by nandrolone in 29% and combination therapy in 12.9%. Overall, HI was observed in 54.8% of patients (n=17). Regarding lineage-specific responses, erythroid HI (HI-E) was achieved in 51.6%, platelet HI (HI-P) in 35.5%, and neutrophil HI (HI-N) in 25.8% of cases. Among patients who were red blood cell transfusion-dependent at baseline, 41.9% achieved transfusion independence. Platelet transfusion independence was achieved in 22.6% of patients. The median time to first documented hematologic response was 71 days (range 1-761). Erythropoietin was used concomitantly in 54.8% of patients (n = 17). During a median follow-up of 7 months, only two deaths were observed, and no patients progressed to higher-risk MDS or AML. The cumulative incidence of hematologic improvement reached 63.4% at 300 days, while non-relapse mortality (NRM) remained low at 4%. Despite the limited number of events, estimated overall survival was 100% at 6 months, 85.7% at 1 year, and 68.6% at 2 years. These estimates should be interpreted with caution due to the small number of deaths and limited long-term follow-up. Male sex was independently associated with a significantly lower rate of HI (HR = 0.08; 95% CI: 0.02–0.32; p = 0.0003). Higher ANC at diagnosis was positively associated with HI (HR = 1.0003; 95% CI: 1.000–1.001; p = 0.048). Compared to danazol alone, the use of nandrolone was associated with a lower hazard of HI (HR = 0.21; 95% CI: 0.05–0.95; p = 0.043), while the combination of both agents significantly increased the probability of achieving HI (HR = 8.72; 95% CI: 1.26–60.5; p = 0.029). Other variables, including age, IPSS-R, hemoglobin, and platelet count at diagnosis, were not significantly associated with HI.

Conclusions:

More than half of the patients treated with androgen therapy achieved HI within a median of two months. These results support the potential role of androgens in select patients and reinforce their utility in resource-limited settings or in patient's ineligible for other disease-modifying therapies.The relatively low incidence of death without hematologic response may illustrate a subgroup of non-responding patients who could still benefit from extended androgen therapy or alternative treatments.The low incidence of disease progression and favorable survival outcomes underscore the potential benefit of androgen therapy in this population.Future prospective studies are needed to define predictive markers of response and to explore the role of combination androgen therapy in MDS.