Novel therapy for managing TP53 Mutated Myelodysplastic Syndrome
TP53 mutation is found in 5-10% of patients with de novo MDS and 20-30% of those with therapy-related MDS and is seen to confer a poorer prognosis. P53-targeted therapy has long been sought. The authors of this article demonstrate some understanding of the process of oncogenesis resulting from TP53 mutation in MDS and introduce a new agent (APR-246), currently in clinical trial, which shows promise in managing TP53 mutated MDS.
Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry
This large registry study of chelated vs non-chelated patients with low risk MDS demonstrated a significant improvement in overall survival for patients undergoing iron chelation. The strength of this study was the inclusion of “real world” MDS patients with a mean age of 70+. Chelated patients were more likely to experience an erythroid response and lower transfusion burden, supporting other studies suggesting iron chelation has a beneficial effect on haematopoiesis.
MYELODYSPLASTIC SYNDROMES: Genetics of MDS
With the use of advanced genomics this article provides a comprehensive registry of driver mutations recurrently found in MDS patients and correlates these with disease phenotype and prognosis.
Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes
Immune checkpoint molecule upregulation is seen as an important mechanism of azacitidine resistance and has been the basis of clinical trials investigating the use of hypomethylating agents in combination with immune checkpoint blockade. This article discusses the scientific background behind this approach to therapy in acute myeloid leukaemia and myelodyslastic syndrome.
Effects of erythropoiesis-stimulating agents on overall survival of International Prognostic Scoring System Low/Intermediate-1 risk, transfusion-independent myelodysplastic syndrome patients: a cohort study
This letter to the editor summarises a study used to assess the impact of erythropoiesis-stimulating agents (ESA) treatment on overall survival and on the evolution of MDS into acute myeloid leukaemia.
The Medalist Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions
This Phase 3 randomized double-blind placebo controlled study demonstrated that treatment with luspatercept resulted in a significantly reduced transfusion burden compared with placebo. Luspatercept is thought to work by accelerating the maturation of red cells, thus reducing red blood cell transfusion requirements in patients with anaemia due to IPSS-R very low-, low-, or intermediate-risk MDS with ring sideroblasts who require red blood cell transfusions.
Update on the pathologic diagnosis of chronic myelomonocytic Leukemia
Daniel A. Arber Attillio Orazi
This is a review of the current diagnostic criteria for chronic myelomonocytic leukaemia which now incorporates the use of molecular genetic studies, helping to inform prognosis.
Targeting TP53 Mutations in Myelodysplastic Syndromes
David Sallman, MD
Assistant Member, Malignant Hematology Department
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Mutation Clearance after Transplantation for Myelodysplastic Syndrome
Minimal residual disease monitoring in haematological malignancies is seen as standard of care in the evaluation of response to treatment and the prediction of relapse risk. This article considers the potential benefit of molecular monitoring after transplantation for myelodysplastic syndrome.