Myelodysplastic Syndrome

P2, N=68, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting

P2, N=40, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting

P2/3, N=116, Completed, Byung-Sik Cho | Unknown status --> Completed

P2, N=68, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting | Trial completion date: Feb 2023 --> Mar 2026

P=N/A, N=60, Recruiting, University of Leipzig | N=134 --> 60

P1/2, N=36, Recruiting, Groupe Francophone des Myelodysplasies | Not yet recruiting --> Recruiting

P1/2, N=40, Suspended, Sclnow Biotechnology Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=30, Recruiting, University of Southern California | Not yet recruiting --> Recruiting

Most importantly, mice transplanted with Casp8-/- BM cells developed MDS-like disease within 4 months of transplantation as demonstrated by anemia, thrombocytopenia and myelodysplasia. Our study suggests an essential role for a balance in Casp8, Ripk3-Mlkl and Ripk1-Tbk1 activities in the regulation of survival and self-renewal of HSPCs, the disruption of which induces inflammation and BM failure, resulting in MDS-like disease.

The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission...CONCLUSIONS The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy.

P1, N=13, Active, not recruiting, University Health Network, Toronto | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Jun 2021 --> Jun 2024

P1, N=30, Active, not recruiting, Otsuka Pharmaceutical Co., Ltd. | Trial completion date: Dec 2023 --> Jan 2026 | Trial primary completion date: Dec 2023 --> Jan 2026

P2, N=59, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P2, N=16, Active, not recruiting, Robert Redner, MD | Completed --> Active, not recruiting | Trial completion date: Feb 2023 --> Dec 2028

P1/2, N=112, Not yet recruiting, Apollo Therapeutics Ltd

No abstract available

Lower-risk MDS (LR-MDS) treatment ranges from observation to supportive measures and erythropoiesis-stimulating agents (ESAs), with emerging therapies like luspatercept showing promise...Emerging treatments, including oral HMAs and novel agents targeting FLT3, and IDH 1/2 mutations, show promise. Future research should refine treatment strategies for this elderly population focusing on quality-of-life improvement.

Fifty-two percent of patients received anti-thymocyte-globulin-based graft-versus-host disease prophylaxis, 32% calcineurin-inhibitor-based prophylaxis, and 7% post-transplant cyclophosphamide-based prophylaxis...This exploratory finding has to be validated in an independent data set. In summary, the existing body of evidence is not (yet) consistent enough to recommend use of donor KIR genotype information for donor selection in routine clinical practice.

P2, N=20, Completed, Seoul National University Hospital | Unknown status --> Completed | N=40 --> 20 | Trial completion date: Jun 2020 --> Jul 2023 | Trial primary completion date: Jun 2019 --> Jul 2023

P2, N=196, Recruiting, Kirsten Grønbæk | Trial completion date: Sep 2027 --> Dec 2027 | Trial primary completion date: Sep 2024 --> Dec 2025

P=N/A, N=300, Enrolling by invitation, The First Affiliated Hospital of Soochow University | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=15, Terminated, Shanghai Antengene Corporation Limited | N=59 --> 15 | Trial completion date: Mar 2024 --> Sep 2023 | Active, not recruiting --> Terminated; The study was stopped early because the sponsor decided to change the study-drug development strategy

Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

AML cases defined by differentiation (WHO2022) and AML not otherwise specified (ICC) are categorized as lacking specific defining genetic abnormalities, WHO2022 labels this as a myeloid neoplasm post cytotoxic therapy (MN-pCT), described as an appendix after specific diagnosis. Similarly, in ICC, it can be described as "therapy-related", without a separate AML category.

Myelodysplastic syndromes (MDS) patients with DEAD-box helicase 41 (DDX41) mutations have been reported to be treated effectively with lenalidomide; however, there are no randomized studies to prove it. We retrospectively analyzed the genetic features and clinical characteristics of these patients. Our findings suggest that MDS patients with DDX41 mutation may benefit from the therapy, for six subjects received this regimen as initial therapy and five of the six subjects achieved complete remission.

Additional characteristic observations included pigmentary deposition in approximately half of the cases and skeletal difficulties in one-quarter. We propose that early diagnosis of patients who exhibit relatively mild phenotypes of skin or skeletal lesions is important for managing and improving the quality of life of patients with AMeD syndrome.

Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

No abstract available

P=N/A, N=144, Recruiting, Rigshospitalet, Denmark | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2026 --> Dec 2025

P2, N=20, Recruiting, University of Florida | Not yet recruiting --> Recruiting

P1/2, N=0, Withdrawn, Novartis Pharmaceuticals | N=63 --> 0 | Not yet recruiting --> Withdrawn

P1, N=100, Not yet recruiting, Byondis B.V.

P1, N=24, Not yet recruiting, OHSU Knight Cancer Institute

P1/2, N=30, Recruiting, Shenzhen TargetRx, Inc. | Not yet recruiting --> Recruiting

P=N/A, N=104, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting

There has been import of the IDH1 inhibitor ivosidenib, initially approved for AML; the Bcl-2 inhibitor venetoclax and liposomal daunorubicin/cytarabine (CPX-351) are under active investigation as well. Unfortunately, effective treatment of TP53-mutated disease remains elusive, though preliminary evidence suggests improved outcomes with oral decitabine/cedazuridine over parenteral hypomethylating agent monotherapy. Investigational agents with novel mechanisms of action may help expand the repertoire of treatment options for HR-MDS and trials continue to offer a hopeful therapeutic avenue for suitable patients.

P=N/A, N=100, Not yet recruiting, Centre Hospitalier Universitaire de Nice

Our study is the first to identify a novel model using FRGs to predict the risk of developing MDS. FRGs may be implicated in MDS pathogenesis through immune-related pathways. These findings highlight the intricate correlation between ferroptosis and MDS, offering insights that may aid in identifying potential therapeutic targets for this debilitating disorder.

P1, N=255, Recruiting, Orca Biosystems, Inc. | Trial completion date: Apr 2028 --> Jul 2026

P=N/A, N=21, Recruiting, Centre Hospitalier Universitaire de Saint Etienne | Phase classification: P2 --> P=N/A | Trial primary completion date: Dec 2023 --> Apr 2024

P=N/A, N=38, Completed, Qianfoshan Hospital | Recruiting --> Completed | N=60 --> 38 | Trial completion date: May 2024 --> May 2023 | Trial primary completion date: Dec 2023 --> May 2023