Adoptive cellular therapies in multiple myeloma.

Plasma cell myeloma (multiple myeloma) is a blood cancer characterized by the clonal proliferation of plasma cells in the bone marrow. Treatment strategies evolve year by year, new drugs getting Food and Drug Administration (FDA)-approved each year. Chimeric antigen receptor (CAR) therapies are an advanced form of immunotherapy that engineer T cells to recognize and destroy cancer cells.

Adoptive cellular therapies in non-Hodgkin lymphomas.

Lymphomas are a group of malignant proliferations of B, T or NK-lymphoid cells at different stages of maturation. While they primarily occur in lymph nodes or lymphatic tissues, they can also involve bone marrow, blood, or other organs. Despite advances in treatment, many patients experience relapse, or develop refractory disease, prompting the development of new therapies.

Shear Wave Elastography for Distinguishing Cervical Lymph Node Malignancy: A Prospective, Observational Study.

: Differentiating between benign and malignant cervical lymph nodes (LNs) is a critical challenge in the clinical setting. We assessed the ability of shear wave elastography (SWE) to distinguish between lymphomas and solid tumor metastases presenting as cervical adenopathy. : We performed a single-center, prospective, observational study in adults with clinically suspicious cervical lymph nodes.

Challenges in the preclinical design and assessment of CAR-T cells.

The advent of immunotherapy in the treatment of cancer has opened a new dimension in the management of this complex multifaceted disease, bringing hope to many patients whose tumors have failed to respond to conventional therapies. The adoptive T cell therapy has since been extended to the treatment of several hematologic malignancies, initially in relapsed settings and more recently at the forefront of treatment due to high response rates. Despite exciting initial results, the preclinical antitumor effects of the first long-term studies show that CAR (Chimeric Antigen Receptor)-T cells have been slow to translate to the clinical setting, with early clinical trials showing suboptimal responses.

Targeting degradation of IKZF1 and IKZF3 through modulation of the E3 ligase substrates in the context of cellular therapies for multiple myeloma.

Multiple myeloma (MM) is a blood cancer characterized by the clonal evolution of plasma cells. In 2022, there were an estimated 118 000 MM cases and 121 000 deaths worldwide. The treatment landscape of MM has undergone a dramatic transformation in recent decades, shifting from conventional chemotherapy to more targeted approaches.

Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune therapies.

A hallmark of cancer biology is resistance to apoptosis. BCL-2 is an anti-apoptotic molecule that is being overexpressed in several myeloid diseases, such as acute myeloid leukemia and myelodysplastic syndromes, but also in several lymphoid cancers, such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphomas and multiple myeloma. Venetoclax (VEN) is a BCL-2 small molecule inhibitor.

Humanized mouse models in MDS.

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem cell disorders defined by ineffective hematopoiesis, multilineage dysplasia, and risk of progression to acute myeloid leukemia. Improvements have been made to identify recurrent genetic mutations and their functional roles, but translating this into preclinical models is still difficult. Traditional murine systems lack the human-specific cytokine support and microenvironmental support that is necessary to reproduce MDS pathophysiology.

SERS-based detection of DNA methylation for cancer diagnosis: Cation-mediated adsorption to silver nanoparticles.

The high-throughput analysis of DNA methylation markers by label-free surface-enhanced Raman scattering (SERS) holds significant promise for advancing cancer detection. However, a deeper understanding of the factors governing DNA adsorption onto metal surfaces and the identification of reliable SERS bands indicative of DNA methylation levels are still needed. In this study, we evaluated the effects of several cations (Ca2+, Mg2+, Al3+, Be2+, Zn2+, Cu2+, Fe2+, and Na⁺) on the SERS signal of DNA and identified Ca2+ as providing the highest enhancement.

A Mathematical Model of Clonal Hematopoiesis Explaining Phase Transitions in Chronic Myeloid Leukemia.

This study presents a mathematical model describing cloned hematopoiesis in chronic myeloid leukemia (CML) through a nonlinear system of differential equations. The primary objective is to understand the progression from healthy hematopoiesis to the chronic and accelerated-acute phases in myeloid leukemia. The model incorporates intrinsic cellular division events in hematopoiesis and delineates the evolution of chronic myeloid leukemia into five compartments: cycling stem cells, quiescent stem cells, progenitor cells, differentiated cells, and terminally differentiated cells.

Insights into Pediatric -Related MDS: Unveiling Challenges in Clinical Practice.

-related myelodysplastic syndrome (-MDS) is a unique predisposition syndrome with a high risk of leukemic transformation. This systematic review synthesizes current literature and presents two illustrative pediatric -MDS cases. Data retrieval from eight cohort and case-control studies provides comprehensive analysis on disease features, diagnostic complexities, management, and outcomes related to hematopoietic stem cell transplantation (HSCT) in -related myeloid malignancies.

EPYSQLI (SB12; Biosimilar to Reference Eculizumab) in Asian and Non-Asian Patients With Paroxysmal Nocturnal Hemoglobinuria: Subgroup Analysis of a Global Phase III Randomized Controlled Trial.

Introduction: SB12 demonstrated equivalence to reference eculizumab (ECU) in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) in the previous randomized, double-blind, multi-national, crossover, Phase III study.

Methods: The scope of this post-hoc study was subgroup analysis by race to compare the efficacy and safety of SB12 and ECU in PNH patients in the Asian and Non-Asian subgroups of the Phase III study.

Results: Results including lactate dehydrogenase (LDH), number of units of packed red blood cells and safety as primary and secondary endpoints demonstrated comparable efficacy and safety of SB12 and ECU in Asian and Non-Asian PNH patients, in line with the study results in the overall population.

SERS-Based Assessment of DNA Methylation for the Evaluation of Measurable Residual Disease in Acute Promyelocytic Leukaemia.

Acute promyelocytic leukaemia (APL) is a type of acute myeloid leukaemia characterised by the reciprocal translocation t(15;17), which offers a unique possibility for measurable residual disease (MRD) monitoring by PCR amplification of the PML-RARA transcripts. Surface-enhanced Raman scattering (SERS) is a laser molecular spectroscopy technique that allows the rapid analysis of changes in the DNA methylation pattern associated with malignant transformation. In this study involving 49 DNA samples from bone marrow aspirations from patients with APL, we showed that the DNA from MRD-positive samples exhibited lower SERS intensities of the band at 730 cm attributed to adenine.

Real world outcomes with Ibrutinib monotherapy in chronic lymphocytic leukemia: a single center experience.

Introduction: The advent of Bruton's tyrosine kinase (BTK) inhibitors brought about a paradigm shift in the management of chronic lymphocytic leukemia (CLL), by offering a well-tolerated chemotherapy-free approach. Here, we share the experience with ibrutinib of a major Romanian regional cancer center.

Methods: We screened patients treated for CLL in our center over 6 years (2017-2022) and included those who were treated with ibrutinib either in the first line of therapy or in subsequent lines.

Advances in Cell and Immune Therapies for Melanoma.

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure to UV radiation, aging populations, and exposure to teratogen agents. However, diagnosis is more precise, and the increased number of new cases is related to the improved diagnosis tools. Despite better early diagnosis and better therapies, melanoma has remained a significant public health challenge because of its aggressive behavior and high potential for metastasis.

Real-world treatment patterns and health care resource use for patients with myelofibrosis: results from the METER study.

Myelofibrosis (MF), a myeloproliferative neoplasm, was most commonly treated with hydroxyurea (HU) before approval of ruxolitinib (RUX), now the standard of care. Factors that influence real-world MF treatment patterns are not well understood. The METER study was a multi-country, retrospective chart review of MF treatment patterns, treatment effectiveness, and health care resource utilization.

Neuro-toxicities of chemo- and immune-therapies in haematologic malignancies: from mechanism to management.

Chemo- and immune therapies administered to treat haematologic malignancies frequently cause neurologic injury. The adverse events range from mild cognitive impairment and headaches to severe conditions such as seizures, stroke and encephalitis. We performed a comprehensive literature review and report the types, mechanisms, management and prevention of neuro-toxicity resulting from these therapies in subjects who develop these toxic effects.

Therapeutic advances in the targeting of ROR1 in hematological cancers.

Receptor tyrosine kinases (RTKs) are key cell surface receptors involved in cell communication and signal transduction, with great importance in cell growth, differentiation, survival, and metabolism. Dysregulation of RTKs, such as EGFR, VEGFR, HER2 or ROR, could lead to various diseases, particularly cancers. ROR1 has emerged as a promising target in hematological malignancies.

Emergency-Driven Multiple Simultaneous Invasive Procedures in Haemophilia.

Despite the controversies regarding the appropriateness and justification of simultaneous bi- and multi-concomitant surgical procedures, this operative technique is increasingly undertaken for economic reasons. This paper discusses three cases of simultaneous interventions: two involving osteoarticular procedures and one involving a complex approach encompassing general and plastic surgery. The indications in emergency-driven cases are mandatory, life-saving, and limb-saving, and not subject to debate.

"Lazarus Response" When Feto-Maternal Microchimerism Kicks in: Spontaneous Remission in Refractory Primary Mediastinal B Cell Lymphoma Following Twin Pregnancy.

: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies.

Capillary Leak Syndrome Associated with Anaplastic T Cell Lymphoma and Transcutaneous Exudation: An Unusual Presentation.

Capillary leak syndrome is a rare complication of cancer, particularly of hematologic malignancies. The syndrome was first described as an idiopathic entity; however, increasingly, more cases are being reported in association with cancers and other conditions. Diagnosis stems from the recognition of the double paradox, consisting of severe generalized oedema and hypotension, accompanied by hallmark laboratory modifications.

A hypothesis on treatment strategy of severe multicentric Castleman disease with continuous renal replacement therapy.

Castleman disease (CD) is a rare lymphoproliferative disorder, with non-specific clinical manifestations, often delayed diagnosis and treatment, which pose a significant challenge in the present times. Patients diagnosed with this disease have poor prognosis due to the limited treatment options. Multicentric CD occurs at multiple lymph node stations and is associated with a proinflammatory response that leads to the development of the so-called 'B symptoms'.

Looking ahead to targeting macrophages by CAR T- or NK-cells in blood cancers.

Introduction: The bone marrow microenvironment (BME) is critical for healthy hematopoiesis and is often disrupted in hematologic malignancies. Tumor-associated macrophages (TAMs) are a major cell type in the tumor microenvironment (TME) and play a significant role in tumor growth and progression. Targeting TAMs and modulating their polarization is a promising strategy for cancer therapy.