Hematological Malignancies

We showed the efficacy of daratumumab in combination with targeted therapies for the treatment of pulmonary MM.

This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported.

Of course, we also focused on infection biomarkers that are not yet used in blood cancer patients but could be used as a future research direction, e.g., human neutrophil lipocalin, serum amyloid A, and heparin-binding protein et al. Finally, clinicians need to combine multiple infection biomarkers, the patient's clinical condition, local susceptibility to the type of infection, and many other factors to make a determination of the type of infection.

Misdiagnosis or late diagnosis of this clinically heterogeneous BPDCN may lead to systemic spread and poor outcomes. Hence, prompt diagnosis and treatment are essential, with a multidisciplinary approach.

Per-residue decomposition plots also revealed high energy contributions in the interactions' binding sites residues. These results indicate that the cytotoxic prospects of the isolated compounds against leukemia as indicated by its molecular interactions with FLT3 and MLV.

Moreover, this increase disappears in CML patients after treatment with tyrosine kinase inhibitors when the curative effect was satisfactory. We conclude that an increase in the proportion of CD56briCD38+ neutrophil subsets exceeding 2.0 % of total neutrophils serves as a highly sensitive and specific flow cytometry marker, enabling rapid and accurate identification of CML.

Despite the typically benign nature of extraosseous Ewing tumors, they can rarely metastasize in less than 20% of cases, as exemplified by this rare case. Accurate diagnosis requires a combined clinic-radio-immunohistochemical approach, and general practitioners should be aware of this clinical entity in neck masses considering its variable clinical presentation and poor prognosis in certain patient's population.

In this exciting and rapidly evolving treatment landscape, this review evaluates the most recent clinical and preclinical data pertaining to these new cellular immunotherapies and explores strategies to overcome resistance pathways. On the protracted journey to a long-term cure, we outline the challenges that lie ahead and ask, 'Are we there yet?'

More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.

Our findings indicated that CagA and NFATc1 cooperatively participate in the lymphomagenesis of HPE-responsive gastric MALT lymphoma.

CD3- FAS- CAR T cells outperformed CD3- B2M- CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of CD3- FAS- allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer.

After combining cytospin- and flow cytometry (FCM) data with miR-181a expression, we could stratify previously ambiguous cases and reclassify patients into a CNS-positive/miR-significant group (mean ± SE for miR-181a copies: 3300.70 ± 809.69) bearing remarkable infiltration as well as into CNS-minimal/miR-significant and CNS-minimal/miR-minimal groups differentiating putative, clinically significant occult CNSL cases (2503.50 ± 275.89 and 744.02 ± 86.81 copies, respectively, p = 1.13 × 10-6). In summary, miR-181a expression is a promising biomarker for CNSL detection, facilitating the robust identification of patients who could benefit from intensified CNS-directed therapy.

The combination of p95HER2.CAR T cells and HER2 x CD3 bispecific antibodies lead to a complete regression in three HER2-positive, patient-derived mouse xenografts tumor models. This combination represents a promising strategy to redirect T cells against a subset of HER2-positive tumors.

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

Analyses of multi-spectroscopy and viscosity assays revealed that 4-TM.P binds to DNA in the minor groove mode, which was supported by molecular docking studies. The dynamic stability of the complex was also confirmed using molecular dynamic simulation analyses.

The ROC area under curve (AUC) is 0.98 when predicting relapse within 30 weeks of CR timepoint 2 (N = 20). Furthermore, we demonstrate quantitating VAF below 0.01% is essential for accurate relapse prediction.

P2, N=31, Active, not recruiting, Children's Oncology Group | N=70 --> 31

Human Th1-like Vγ9Vδ2 (γδ) T cells, important effectors against tumors, can be expanded and activated ex vivo by the aminobisphosphonate zoledronic acid in combination with IL-2. These results demonstrate that SLAMF7 is highly expressed in both MM cells and OCs, and that the ex vivo-expanded γδ T cells can exert ELO-mediated ADCC against SLAMF7-expressing MM cells and OCs besides their direct cytotoxic activity. Further study is warranted for the innovative utilization of γδ T cells.

Expression of caIL-12 by tumor-targeting T cells demonstrated therapeutic effect against target-antigen-negative tumor variants, primarily through the induction of antigen spreading. These findings highlight the potential of caIL-12 to address challenges of antigen escape and tumor heterogeneity that may limit the efficacy of T-cell therapy against solid tumors.

P3, N=600, Active, not recruiting, Loxo Oncology, Inc. | Recruiting --> Active, not recruiting

P2; N=50 --> 30 | Recruiting --> Suspended

P2, N=30, Recruiting, The First Affiliated Hospital of Soochow University | Not yet recruiting --> Recruiting

P1/2, N=23, Active, not recruiting, Joshua Brody | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Nov 2026

P1/2, N=280, Active, not recruiting, Kronos Bio | Recruiting --> Active, not recruiting

P1/2, N=26, Completed, Sellas Life Sciences Group | Active, not recruiting --> Completed | N=90 --> 26

P=N/A, N=40, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Nov 2024 | Trial primary completion date: Jun 2025 --> Nov 2024

P2, N=68, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=36, Recruiting, The First Affiliated Hospital of Soochow University | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P1/2, N=0, Withdrawn, Kathleen Dorritie | N=34 --> 0 | Recruiting --> Withdrawn

P1/2, N=36, Active, not recruiting, Theriva Biologics, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2a --> P1/2 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=792, Active, not recruiting, Institut Bergonié | Unknown status --> Active, not recruiting | N=1500 --> 792 | Trial completion date: Feb 2021 --> Mar 2026 | Trial primary completion date: Feb 2019 --> Dec 2023

P2, N=144, Not yet recruiting, Ruijin Hospital

Our results suggest that an integrated NGS strategy should not replace FISH or be routinely used in the workup to detect the clinically relevant rearrangements in HGBCL. It may serve as a complement to FISH testing when FISH shows negative results.

Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

P1/2, N=101, Active, not recruiting, University of Chicago | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=54, Completed, Amgen | Active, not recruiting --> Completed

P1, N=59, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025

P2, N=35, Recruiting, Fred Hutchinson Cancer Center | N=20 --> 35 | Trial completion date: Oct 2026 --> Mar 2027 | Trial primary completion date: Dec 2024 --> Mar 2025

P1, N=13, Recruiting, Wuhan Union Hospital, China

Drug sensitivity analysis revealed altered IC50 values for drugs like 5-fluorouracil and bortezomib. CNN3 and LGR4 were identified as modulators of cAML progression, making them potential therapeutic targets. Future studies with larger cohorts are essential to validate these findings and further explore CRGs-targeted therapies.

Analysis of protein interactions suggested that arginine methylation of p30 C/EBPα differentially determines interactions with SWI/SNF and MLL complexes. Pharmacological targeting of p30 C/EBPα arginine methylation may have clinical relevance in myeloproliferative and inflammatory diseases, in neutropenia, and in leukemic stem cells.

In addition, we show that WBP1L regulates hematopoietic stem cell functionality and leukocyte progenitor proliferation and gene expression during hematopoietic stem and progenitor cell transplantation, which contribute to more efficient engraftment of WBP1L-deficient cells. WBP1L thus emerges as a regulator of hematopoietic stem and progenitor cell function, which controls leukocyte numbers at the steady state and after bone marrow transplantation.