Leukemia & Lymphoma最新文献

MiRNAs have been identified as participants in leukemogenesis by controlling several cellular functions, such as differentiation, proliferation, and apoptosis. Their role in myelodysplastic neoplasms (MDS) pathogenesis is researched due to implementations in early identification, classification, and therapeutical options. IPSS-R, being the most widely used MDS classification, underestimates early biological events that can alter the disease's prognosis. The purpose of this study is to determine whether miRNA levels are aligned to MDS risk stratification groups and can therefore be used as diagnostic biomarkers. To evaluate miRNAs as possible biomarkers, we measured the levels of miR-181a-2-3p, miR-124-3p, miR-550a-3p, miR-155-5p, miR-151a-3p, and miR-125b-5p by a quantitative real-time PCR in bone marrow samples of 41 MDS patients. In conclusion, in myeloid malignancies, genomic characteristics may provide a wider apprehension of its clinical course and prognosis. MiRNAs constitute a possible diagnostic biomarker and therapeutic target, allowing intermediate-risk patients that express high levels of specific miRNAs to be re-classified and receive more advanced therapeutic agents. In our study, an association between high levels of miRNAs and worsening outcomes is established, supporting the need for further incorporation of molecular data into currently used classification systems.

Efforts to produce adoptive cell therapies in AML have been largely unfruitful, despite the success seen in lymphoid malignancies. Identifying targetable antigens on leukemic cells that are absent on normal progenitor cells remains a major obstacle, as is the hostile tumor microenvironment created by AML blasts. In this review, we summarize the challenges in the development of adoptive cell therapies such as CAR-T, CAR-NK, and TCR-T cells in AML, discussing both autologous and allogeneic therapies. We also discuss methods to address myelotoxicity associated with these therapies, including rapidly switchable CAR platforms and CRISPR-Cas9 genetic engineering of hematopoietic stem cells. Finally, we present the current clinical landscape in these areas, along with future directions in the field.

Clinical trials are crucial for improving patient outcomes. Although a significant number of trials are discontinued prematurely, our understanding of factors influencing early termination is limited. We conducted a comprehensive search of ClinicalTrials.gov to identify leukemia trials from 2000 to 2020, followed by data abstraction performed by two independent reviewers. Among 3522 leukemia clinical trials identified, 28.4% were terminated prematurely. Slow accrual was the leading cause of termination 38.2%. The termination rate increased significantly from 17.0% between 2000 and 2005 to 30.9% between 2010 and 2015 (p < .001). Large trials had a lower termination rate than small trials (p < .001). Academic-sponsored trials had the highest termination rates compared to other sponsors' trials (p < .001). Early-phase trials showed higher termination rates compared to late-phase (p < .001). Other significant factors included a sequential assignment, single-center, and non-randomized trials (p < .001). Much of leukemia trials are terminated prematurely, with slow accrual being the most common reason for early termination.

Over the past two decades, there has been a continuous improvement in outcome for patients with indolent lymphoma (iNHL) resulting in a gradual accumulation of survivors. While life expectancy in the current era approaches that of the lymphoma-free population, patients continue to experience lifelong complications of the disease and its treatment affecting general health, emotional, psychological and social wellbeing, relationships, employment, finances, and fitness. Contemporary care models while suited to the management of lymphoma are often lacking when it comes to identification and management of these additional needs. Given improvements in physical survival achieved over the past decades, it is timely for us to focus on other issues affecting patient wellbeing including immunodeficiency and infection, second cancers, cardiovascular disease, bone health, psychological wellbeing, and sexual health. Many of these aspects are in the domain of the primary care physician; however, there is limited guidance on how these issues should be addressed. It is now time for us to engage our patients, their caregivers, and other healthcare providers in care aspects beyond the lymphoma diagnosis, so they can anticipate a rich and full life, free from both direct and indirect consequences of the lymphoma diagnosis.

The role of next-generation sequencing (NGS) for minimal residual disease (MRD) assessment in pediatric acute lymphoblastic leukemia (ALL) is still under consideration. Fifty pediatric patients were prospectively evaluated for specific clonal rearrangements of immunoglobulin and T-cell receptor genes using NGS analysis at diagnosis and on days 33 and 78 from therapy onset. The prognostic value or the NGS-MRD status was analyzed after a median follow-up of 4 years. All but one patient with negative NGS-MRD status on day 33 are in clinical remission. A total of 29 (58%) patients were NGS-MRD positive on day 33, of which 9 (18%) patients remained positive on day 78. However, only a small percentage of the patients with positive NGS-MRD status on day 33 and day 78 relapsed: 21% (6/29) and 33% (3/9), respectively. Positive NGS-MRD status is not a reliable prognostic biomarker in children with ALL and warrants careful consideration in disease stratification.

Treatment strategies for early stage diffuse large B-cell lymphoma (ES-DLBCL) include R-CHOP, with a similar schedule to that used in advanced stage, or a reduced number of cycles followed by radiation therapy (RT). We retrospectively analyzed 179 ES-DLBCL patients, managed according to the clinical practice. Treatment regimens include chemoimmunotherapy 4-6 cycles +/- RT as consolidation. First-line therapy was R-CHOP/CHOP-like in 88.8% of cases. RT as consolidation was administered to 29.9% of cases. Complete response rate was 87.2%, median PFS and OS were not reached. IPI 2-3 and first-line regimen with 3-4 cycles of R-CHOP without RT were the 2 prognostic variables for OS in multivariate analysis. After a median follow-up of 48 months, 31 patients died (17.3%). We suggest that both R-CHOP 6 cycles and 3-4 cycles followed by RT as consolidation seem to be valid first-line regimens, while an abbreviated strategy without RT could be associated to inferior outcome.

Minimal residual disease (MRD) has emerged as an important prognostic maker in patients with multiple myeloma at different stages of their treatment. Moreover, it is being increasingly incorporated as an endpoint in various clinical trials. Since maintenance therapy is an integral part of myeloma treatment, especially in the upfront setting post autologous transplantation, it is imperative to understand the role of MRD testing in the maintenance stetting. This review aims to examine the utility and dynamics of MRD testing in order to elucidate its prognostic role and possible incorporation in clinical decision making processes.