Acute Lymphocytic Leukemia

P=N/A, N=27, Completed, University of Erlangen-Nürnberg Medical School | Recruiting --> Completed | N=50 --> 27

Furthermore, MKX upregulated SESN3 and downregulated BCL2L11, which may together underlie decreased etoposide-induced apoptosis...Taken together, our study identified MKX as novel aberrantly expressed homeobox gene in AML and MM, highlighting the function of IRX1 in normal myelopoiesis and B-cell development, and of IRX-related genes in corresponding malignancies. Our data merit further investigation of MKX and its deregulated target genes to serve as novel markers and/or potential therapeutic targets in AML patient subsets.

P2, N=30, Not yet recruiting, University of Washington

In this study, we evaluated the association of NUDT15 *4 with mercaptopurine (6-MP) tolerance in a retrospective cohort of 1,399 patients with acute lymphoblastic leukemia (ALL) of diverse ancestries...In a separate retrospective validation study, six patients were identified as having NUDT15 *1/*4 by routine clinical pharmacogenetics testing and tolerated a 6-MP median dose of 38.7 mg/m2 (IQR, 33.7-54.0), confirming the need for dose reduction attributed to the NUDT15 *4 variant. These results point to the need to include NUDT15 *4 in pharmacogenetics-guided thiopurine dosing algorithms.

Different reports evidenced the interplay between Notch and the anti-apoptotic Bcl-2 family proteins in T-ALL. Although based on early research data, this review discusses recent advances in directly targeting Notch receptors and the use of validated BH3 mimetics for the treatment of T-ALL and their combined action in light of current evidence of their use.

Notably, ctDNA analysis proved to be a superior predictor of MRD compared to PB assessment alone, especially in instances of low disease burden. These findings highlight the potential of ctDNA as a sensitive biomarker for monitoring treatment response and detecting MRD in infant MLL-r ALL.

Upon ruxolitinib withdrawal, TSLPRCART functionality recovered in vivo with clearance of subsequent ALL rechallenge. These translational studies demonstrate an effective two-pronged therapeutic strategy that mitigates acute CART-induced hyperinflammation and provides potential anti-leukemia 'maintenance' relapse prevention for CRLF2-rearranged Ph-like and DS-ALL.

The combined AUC was 0.916 (95% CI: 0.845-0.986), with 0.903 sensitivity and 0.818 specificity, outperforming individual predictors (p < 0.05). Age, CRP, and FIB levels are good early predictors of severe AAP, and their combination significantly improves predictive accuracy.

These findings highlight significant differences in ID1 and ID3 expression levels and their impact on TIME populations, particularly neutrophil-related pathways. The results suggest a potential role for ID1 and ID3 in immune evasion in adult B-ALL, mediated through neutrophil activation and immune regulation.

In conclusion, while ALL that does have CDKN2A/2B gene deletions is associated with certain clinical characteristics and genetic aberrations, they did not significantly impact OS or EFS. Furthermore, subgroup analysis revealed a potential prognostic role of ALL that does have CDKN2A/2B deletions presenting with hepatosplenomegaly on palpation, emphasizing the importance of comprehensive risk stratification in treatment decision-making for this subgroup.

Remarkably, T-ALL cells with an orphan TCRβ chain displayed the strongest stemness and resistance to chemotherapy. Our study provided transcriptome and epigenome characterisation of T-ALL cells categorised by TCR clonotypes, which may be helpful for the development of novel predictive markers to evaluate treatment effectiveness for T-ALL.

P2, N=20, Recruiting, Northside Hospital, Inc. | Not yet recruiting --> Recruiting

P1, N=15, Not yet recruiting, City of Hope Medical Center

P1/2, N=179, Active, not recruiting, AbbVie | Trial completion date: Dec 2025 --> Dec 2026

P1, N=10, Recruiting, Institute of Hematology and Blood Transfusion, Czech Republic | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

These findings confirm the unique utility of the NGS-based RNA fusion panel as a diagnostic tool to identify gene rearrangements that drive haematological malignancies. It can identify novel and rare gene rearrangements to assist with diagnosis, prognostication and treatment decisions.

In this study, we successfully identified possible active ingredients and predicted potential targets and pathways for ZSW for the treatment of ALL. We provide a new strategy for further research on the molecular basis of ZSW biological effects in ALL. In addition, the potential active ingredients could provide new leads for drug discovery in ALL investigations.

These results suggested that Stattic holds promise as a therapeutic agent in T‑ALL by modulating key pathways involved in cell survival and proliferation. In conclusion, Stattic exhibited a significant therapeutic potential for T‑ALL via a dose‑dependent reduction of cell viability, inhibiting STAT3 phosphorylation, and promoting both apoptotic and autophagic cell death; however, further studies are required before clinical application.

P2, N=20, Recruiting, Northside Hospital, Inc. | Trial completion date: Aug 2025 --> Dec 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Starting from the initiation of blinatumomab treatment, with a median follow-up of 12 months, all patients remained in complete remission. Our study was the first to demonstrate that blinatumomab could further eradicate ddPCR MRD after patients achieve MFC-MRD undetectable status in B-ALL patients.

Not available.

P2, N=20, Recruiting, Eastern Cooperative Oncology Group | Trial completion date: Oct 2024 --> Jun 2027 | Trial primary completion date: Oct 2024 --> Jun 2027

P1, N=19, Terminated, M.D. Anderson Cancer Center | Active, not recruiting --> Terminated; Administratively Complete

P2/3, N=745, Completed, Universitätsklinikum Hamburg-Eppendorf | Active, not recruiting --> Completed

Additionally, TGF-β demonstrated exceptional accuracy (AUC 0.995) as a potential marker, with 100% sensitivity and 96% specificity. These findings suggest that TNF-α and TGF-β may be associated with ALL susceptibility, though further research with larger and more diverse populations is necessary to confirm these results.

Therapeutically relevant doses of CD19/CD22 CAR-T cells can be successfully manufactured from whole blood. On average, 80 mL of whole blood yields enough CAR-T cells to create a single dose for a pediatric patient (50 kg) at a dosage of 1 × 106 CAR-T cells/kg. For larger patients, scaling up is straightforward by collecting a larger blood volume. This method also demonstrates a cost-effective approach to T cell activation and expansion which, alongside a more straightforward collection of whole blood, makes it more widely accessible especially for middle- and low-income countries. By reducing costs and labor, this strategy has the potential to significantly expand global access to CAR-T cell therapy.

P=N/A, N=40, Recruiting, Children's National Research Institute

P1/2, N=81, Recruiting, University of Sao Paulo | Not yet recruiting --> Recruiting

P=N/A, N=90, Active, not recruiting, Assiut University

P1, N=3, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jan 2026 --> Mar 2025

Here we report the case of a child with DS who was diagnosed with a second relapse of BCP-ALL and has maintained complete remission through regular single-agent InO therapy. Single-agent maintenance using InO can be a good option to avoid subsequent relapse in patients with relapsed or refractory BCP-ALL who cannot proceed to allo-HCT and require less-toxic treatments.

Lenalidomide, a derivative of thalidomide, is a type of immunomodulatory drug (IMiD) that has been standard therapy for multiple myeloma (MM) and other hematologic malignancies for almost two decades. In addition, treatment with IMiDs is also associated with an increased risk for myelodysplastic neoplasms (MDS), squamous cell carcinoma of the skin, and, less frequently, acute lymphoblastic leukemia (ALL). We present a case of an elderly male with MM and multiple subsequent skin cancers, who presented with pancytopenia and was diagnosed with B-lymphoblastic leukemia (B-ALL) after 10 years of maintenance lenalidomide therapy.

Specifically, we observed a significant decrease in cytokine levels (e.g., TNF-α, IL-1β, IL-6, and IL-8) following the initiation of treatment, highlighting the influence of leukemia burden on systemic inflammation. The results support the utilization of EVs as a sensitive marker of oxidative stress and off-target tissue damage.

All patients had persistent NGS MRD post-induction, which is markedly lower than the reported 20-25% NGS undetectable MRD rate in B-ALL post-induction. Persistent NGS MRD has low PPV for relapse in T-ALL, which limits its utility in clinical decision making for this population.

Incorporation of blinatumomab and/or inotuzumab in CR1 may mitigate the negative prognostic significance of MRD, however it is unclear if intensity of standard post-remission therapy can be safely reduced without compromising outcomes...We designed a phase I clinical trial to determine safety and tolerability of UCD19 CAR-T cell therapy for adults with B-ALL in MRD+ CR1 who are at high risk for relapse.Methods : Eligible patients include adults (≥18yo) with B-ALL in CR1 after induction therapy, with MRD positivity by either flow cytometry or NGS (Clonoseq)...Longer follow-up is needed to determine if remissions remain durable, and to determine the relationship between functional persistence (as measured by B-cell aplasia) and remission durability. Enrollment is ongoing at DL2.

Translation of our findings to the human system showed that high expression of LY6E on tumour cells impaired their physical interaction with NK cells and led to worse prognosis in leukaemia patients. Our results demonstrate that tumour cells are actively edited by NK cells during the equilibrium phase and use different avenues to escape NK cell-mediated eradication.

P=N/A, N=60, Not yet recruiting, National Research Center for Hematology, Russia

P1, N=40, Completed, Baylor College of Medicine | Active, not recruiting --> Completed

P1, N=3, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=88 --> 3

In addition, all T-LBLs demonstrate constitutive expression of pAKT, indicating the presence of activated AKT signaling, and are sensitive to treatment with the pan-AKT inhibitor MK-2206, suggesting that these lymphomas are dependent on pAKT signaling for their survival. Lastly, ATM-deficiency itself does not cause loss of PTEN or dysregulated AKT signaling, as ATM-deficient non-malignant thymocytes express wild-type levels of PTEN and lack detectable pAKT. This study demonstrates for the first time that the majority of ATM-deficient thymic T-LBLs lose PTEN expression and all depend on AKT signaling for survival, suggesting their potential use as an animal model for PI3K/AKT/MTOR pathway dysfunction in human T-ALL.

CD10, CD20, and CD200 were valuable in distinguishing MRD-positive cases from MRD-negative cases. Moreover, the MRD "lite" panel had 100% concordance between the two observers, suggesting simplicity in assessment and, hence, wider applicability.

The complete remission (P = 0.48) and the overall survival rates were similar (P >0.05). Except for an increased rate of acute leukaemia and a lower platelet count, the COVID-19 pandemic did not impact the presentation and outcomes of acute leukaemia.