News and Treatment Updates | Aplastic Anemia and MDS International Foundation (AAMDSIF)

News and Treatment Updates

Here's where you'll find a regularly updated, broad range of articles written by the AAMDSIF team, allied health organizations and news organizations. By staying well-informed, patients and families are practicing a form of self-support that will help them be more effective self-advocates when engaging with health care providers.

Pre-transplant inflammation and its associations with acute GvHD and mortality in pediatric allogeneic hematopoietic stem cell transplantation patients

Originally Published: 05/12/2025
Abstract In this explorative study we aimed to identify inflammatory serum proteins measured before allogeneic hematopoietic stem cell transplantation (HSCT) that are associated with acute Graft-versus-Host Disease (aGvHD) and mortality in pediatric HSCT recipients. We measured 28 inflammatory serum proteins in 384 pediatric patients (2010–2022) with malignant (30%) and non-malignant (70%) indications for allogeneic HSCT. A sample before the start of the conditioning (T1) was included, as well as a sample on the day of HSCT (T2). For patients who developed aGvHD we also included a sample at...

Reduced venetoclax exposure to 7 days vs standard exposure with hypomethylating agents in newly diagnosed AML patients

Originally Published: 04/17/2025
Abstract Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days (“7 + 7” regimen) from the first cycle (n = 82) vs patients treated...

Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes

Originally Published: 04/11/2025
Abstract Dissecting the preneoplastic disease states’ biological mechanisms that precede tumorigenesis can lead to interventions that can slow down disease progression and/or mitigate disease-related comorbidities. Myelodysplastic syndromes (MDS) cannot be cured by currently available pharmacological therapies, which fail to eradicate aberrant hematopoietic stem cells (HSCs), most of which are mutated by the time of diagnosis. Here, we sought to elucidate how MDS HSCs evade immune surveillance and expand in patients with clonal cytopenias of undetermined significance (CCUS), the pre-...

Cell-autonomous dysregulation of interferon signaling drives clonal expansion of SRSF2-mutant MDS stem/progenitor cells

Originally Published: 03/31/2025
Key Points SRSF2 mutations blunt responsiveness of MDS cells to IFN stimulation and promote their clonal fitness by downregulating STAT1 expression Proteasome inhibition restores STAT1 protein level and sensitivity of SRSF2-mutant MDS cells to IFN, suggesting a new therapeutic strategy Myelodysplastic syndromes (MDS) are myeloid malignancies often driven by mutations in genes encoding splicing factors (SFs). How these mutations drive the clonal expansion of MDS stem/progenitor cells to outcompete normal hematopoietic stem/progenitor cells (HSPCs) remains unexplained. Although a role for...

TP53-Mutated Acute Myeloid Leukemia and Blast Phase Myeloproliferative Neoplasm: Distinct Mutation Leads to Poorer Prognosis

Originally Published: 03/28/2025
ABSTRACT Patients with TP53 mutations in acute myeloid leukemia (AML) and blast phase myeloproliferative neoplasms (MPN-BP) experience similar poor clinical outcomes. A retrospective analysis of 39 patients with TP53 mutations (23 with AML and 16 with MPN-BP) revealed comparable mutation patterns associated with prognostic significance. A total of 47 distinct TP53 mutations were identified, including seven patients with multiple mutations. Based on clinical outcomes, we propose a two-tiered risk stratification for TP53-mutated AML and MPN-BP. The high-risk group mutations, such as splice...

Venetoclax and azacitidine in untreated patients with therapy-related acute myeloid leukemia, antecedent myelodysplastic syndromes or chronic myelomonocytic leukemia

Originally Published: 03/28/2025
Dear Editor, Secondary acute myeloid leukemia (sAML), a subset of AML, may arise from antecedent hematologic disorders (antecedent myelodysplastic syndrome or chronic myelomonocytic leukemia [A-MDS/CMML]) or complication of prior cytotoxic chemotherapy or radiation therapy (therapy-related AML [tAML]) [1]. It comprises about 25% to 35% of AML cases, occurring more frequently with age [2]. Rising incidence of sAML is potentially related to increased survival from prior malignancies, greater use of chemotherapy, and improved reporting of myeloid malignancies [2]. sAML is frequently associated...

How I treat secondary acute myeloid leukemia

Originally Published: 03/20/2025
Abstract Secondary acute myeloid leukemia (sAML) has traditionally been used to designate any AML disease arising from an antecedent hematologic disorder or after prior cytotoxic or radiation therapy. We now know sAML comprises multiple disease entities with distinct clinical and biological features: AML, myelodysplastic related; myeloproliferative neoplasm-blast phase; and AML post–cytotoxic therapy. These entities largely represent adverse-risk phenotypes with the majority of patients experiencing suboptimal outcomes with standard therapeutic options. Given the aging general population and...

How I use maintenance therapy in acute myeloid leukemia

Originally Published: 03/20/2025
Abstract Outcomes for acute myeloid leukemia (AML) have improved significantly in the past decade with the approval of novel therapeutics targeting diverse vulnerabilities of leukemic cells, expanded access to stem cell transplantation, and improved safety of transplantation. Although attainment of initial remission is now an expected outcome in most patients with AML receiving intensive or nonintensive induction regimens, maintaining long-term remission and decreasing the risk of relapse remain critical challenges. Maintenance approaches using assorted agents have yielded variable success...

Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes

Originally Published: 03/13/2025
Abstract Outcomes are poor in patients with higher-risk myelodysplastic syndromes (HR MDS) and frontline treatment options are limited. This phase 1b study investigated safety and efficacy of venetoclax, a selective B-cell lymphoma 2 inhibitor, at the recommended phase 2 dose (RP2D; 400 mg for 14 days per 28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days per 28-day cycle) for treatment-naive HR MDS. Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR),...

Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia With Myelodysplasia-Related Genetic Features: Relevance of the Genetic Underlying Category. A Retrospective Analysis on Behalf of the Acute Leukemia Working Party of the

Originally Published: 03/10/2025
ABSTRACT Patients (pts) with myelodysplasia-related AML (MR-AML) are now genetically recategorized, with three different groups in the International Consensus Classification: AML with mutated TP53 (TP53-AML), with myelodysplasia-related gene mutations (MR-GM AML), and with myelodysplasia-related cytogenetic abnormalities (MR-CG AML). Moreover, TP53-AML is determined by the presence of an additional complex karyotype (TP53-mut CK and non-CK AML, respectively). Nonetheless, the relevance of this classification to transplantation outcomes is largely unknown. We analyzed the outcomes of pts....