Chronic Eosinophilic Leukemia

The FMF-02 trial is the first randomized phase IIb study directly comparing the novel inhibitor FM against RUX. Its findings are expected to generate pivotal evidence regarding whether FM offers superior or differentiated clinical benefits, thereby informing its potential as a frontline therapy for intermediate- to high-risk MF and guiding the design of future phase III studies.

The use of ACEi does not seem to mitigate disease-related symptoms in MPNs. Prospective randomized trials are needed to fully elucidate their therapeutic potential in MPNs.

IL-5 CAR-T cell therapy represents a promising targeted therapeutic approach for IL-5Rα+ hypereosinophilic disorders. Its ability to target eosinophils and their precursors across all developmental stages in BM and PB addresses a critical unmet medical need in refractory HES and CEL.

P=N/A, N=300, Recruiting, Azienda Ospedaliero-Universitaria di Parma

Emerging immunomodulatory therapies-such as interferon-α, Janus kinase (JAK) inhibitors, and other immunoregulatory agents-have demonstrated efficacy primarily by restoring immune balance. This review outlines the dual roles of immune cells and cytokines in MPN pathophysiology, emphasizes the significance of immune yin-yang imbalance, and evaluates current and prospective immunotherapeutic strategies for targeted immunologic intervention.

P=N/A, N=153, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2025 --> Dec 2026

Both in vitro and in vivo studies demonstrate that Ca@CMPN effectively inhibits tumor growth and reprograms the TME, as evidenced by enhanced dendritic cell maturation, activation of cytotoxic T cells, and elevated levels of pro-inflammatory cytokines (interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)). This work presents a paradigm-shifting strategy that synergizes ion-interference therapy with hydrogen immunotherapy, offering a powerful nanoplatform to unlock the full potential of cancer immunotherapy.

TSI and JAK2 VAF outperform ferritin as diagnostic markers to differentiate PV from ET. Integrating functional iron parameters with molecular data improves diagnostic accuracy, particularly in clinically ambiguous cases, and supports their inclusion in MPN diagnostic algorithms.

IGH CDR3 sequencing supported age-dependent pruning of the B cell repertoire, and cytogenetic and next-generation analyses uncovered preclinical clonal lymphoma-associated changes in nearly all POT1 variant carriers older than 60 (9 of 10). Our data identify extended cellular longevity due to long TL as an inherited risk factor for lymphoma explaining its syndromic association with solid tumors, and in some cases, myeloproliferative neoplasms.

Metformin treatment reduced bone marrow collagen deposits, downregulated the STAT pathway and reduced the p85 subunit of PI3K enzymatic complex, together with endothelial maintenance genes, in PMF patients. These results raise new evidence regarding metformin, a cheap and widely available drug, as a possible adjuvant for the treatment of PMF patients.

P2, N=10, Recruiting, William Shomali | Trial completion date: Nov 2025 --> Dec 2028 | Trial primary completion date: Nov 2025 --> Dec 2028

MF plasma increased megakaryocyte output, which was attenuated in sequential samples from ruxolitinib-treated patients...Elevated levels of circulating RANTES correlated with ET plasma-induced proplatelet formation, which was partially reverted by RANTES receptor CCR5 antagonist Maraviroc, indicating RANTES is involved in this process. These findings indicate that, in addition to clonal mutations, extrinsic inflammatory mediators play a direct role in MF and ET megakaryocyte abnormalities. The distinct cytokine profile could potentially be useful for the development of targeted therapies.