Search

Over the past three decades, the treatment of lymphoproliferative disorders has undergone profound changes, notably due to the increasing availability of innovative therapies with the potential to redefine clinical management paradigms. A major impact is related to the development of monoclonal antibodies, checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cell therapies. This review discusses the current landscape of clinical trials targeting various hematological malignancies, highlighting promising early-phase results and strategies to overcome resistance. Lymphoproliferative disorders encompass a range of conditions: while in Hodgkin lymphoma (HL) the goal is to reduce chemotherapy-related toxicity by integrating immunotherapy into the frontline setting, peripheral T cell lymphoma (PTCL) lacks effective targeted therapies. The review emphasizes a shifting therapeutic landscape towards precision medicine and treatment modalities that are less toxic yet more effective. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphoproliferative disorders are commonly observed in the elderly population and usually their treatment can cause numerous side effects, loss of autonomy and impaired quality of life. The management of these patients, when a curative treatment is proposed, needs to be personalized according to subject, disease and treatment features. Nowadays, in order to reduce the impact of toxicities, supportive therapy is a crucial ally during the administration of chemo-immunotherapy. Particularly, the prevention of hematological and infectious complications, tumor lysis syndrome and cardiovascular and neurological events could lead not only to improved oncological outcomes but also to improved quality of life. The treatment paradigm in older patients with malignant hemopathies is the choice between an effective conservative treatment that preserves quality of life and an intensive, potentially curative treatment with more toxicities. For each patient, it is important to determine the risk/benefit ratio. The patient should be involved in the discussion, sufficiently informed and able to express himself and his expectations in terms of quality of life. However, this informed consent is conditioned by the ability of the patient to understand the risks and benefits of the treatment. Decline in quality of life is an important parameter for older patients with cancer and many prospective trials have now confirmed the impact of different side effects of treatment, such as recurrent hospitalization, loss of autonomy in daily activities, loss of contact with grandchildren and loss of cognitive functions. Interventions oriented to vulnerabilities detected in the older patients (by comprehensive geriatric assessment) and an optimal approach, including preventive measures to reduce treatment-related toxicity and mortality, are directly correlated to improvement in quality of life. [ABSTRACT FROM AUTHOR]

Background: Syringomyelia (Syr) in patients with Chiari 1 malformation (CM1) may be attributable to abnormal dynamics of cerebrospinal fluid (CSF) in the upper cervical segment; fourth ventricle enlargement has been reported in association with a worse clinical and radiological presentation, independently of the posterior fossa volume. In this study, we analyzed presurgery hydrodynamic markers to evaluate if their changes could be associated with clinical and radiological improvement after posterior fossa decompression and duraplasty (PFDD). As a primary endpoint, we aimed to correlate improvement in the fourth ventricle area with positive clinical outcomes. Methods: In total, in this study, we enrolled 36 consecutive adults with Syr and CM1 who were followed by a multidisciplinary team. All the patients were prospectively evaluated with clinical scales and neuroimaging, including CSF flow, the fourth ventricle area, and the Vaquero Index by using a phase-contrast MRI before (T0) and after surgical treatment (T1-Tlast, with a range of 12–108 months). The CSF flow at the craniocervical junction (CCJ), the fourth ventricle area, and the Vaquero Index changes were statistically analyzed and compared to the clinical and quality of life improvement after surgery. The good outcome prediction ability of presurgical radiological variables was tested. Results: Surgery was associated with positive clinical and radiological outcomes in more than 90% of cases. The fourth ventricle area significantly reduced after surgery (T0-Tlast, p = 0.0093), but no significant associations with clinical improvement were found. The presurgical presence of CSF flow at the CCJ was able to predict a good outcome (AUC = 0.68, 95% CI 0.50–0.87 and LH+ = 2.1, IC 95% 1.16–3.07) and was also significantly associated with post-surgical pain relief (rho = 0.61 and p = 0.0144). Conclusions: Presurgery CSF flow at the CCJ is proposed as a radiological marker with the ability to predict a positive outcome after PFDD in adults with syringomyelia and CM1. Measurements of the fourth ventricle area could be useful additional information for evaluating surgical long-term follow-up; further experience on larger cohorts is required to better define the prognostic yield of this radiological parameter. [ABSTRACT FROM AUTHOR]

For decades, intensive chemotherapy (IC) has been considered the best therapeutic option for treating acute myeloid leukemia (AML), with no curative option available for patients who are not eligible for IC or who have had failed IC. Over the last few years, several new drugs have enriched the therapeutic arsenal of AML treatment for both fit and unfit patients, raising new opportunities but also new challenges. These include the already approved venetoclax, the IDH1/2 inhibitors enasidenib and ivosidenib, gemtuzumab ozogamicin, the liposomal daunorubicin/cytarabine formulation CPX-351, and oral azacitidine. Venetoclax, an anti BCL2-inhibitor, in combination with hypomethylating agents (HMAs), has markedly improved the management of unfit and elderly patients from the perspective of improved quality of life and better survival. Venetoclax is currently under investigation in combination with other old and new drugs in early phase trials. Recently developed drugs with different mechanisms of action and new technologies that have already been investigated in other settings (BiTE and CAR-T cells) are currently being explored in AML, and ongoing trials should determine promising agents, more synergic combinations, and better treatment strategies. Access to new drugs and inclusion in clinical trials should be strongly encouraged to provide scientific evidence and to define the future standard of treatment in AML. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard treatment for Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease is salvage chemotherapy followed by autologous stem cell transplantation (ASCT). With commonly used chemotherapy combinations, 25–30% fail to proceed to ASCT, with poor outcomes. The aim of this retrospective study was to evaluate the efficacy of brentuximab vedotin (BV) and pembrolizumab combination as a bridge to ASCT in R/R HL patients. We retrospectively collected data from 10 patients, 8 male and 2 female, with a median age of 30.7 years. The median follow-up time was 16.5 months, while the median number of received cycles of treatment was 4 (2–7). Eight patients proceeded to ASCT (80%) and seven of them to subsequent BV maintenance, with two early disease progression (PD). The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients. Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25–30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients presenting with a high-risk, multi-refractory disease. Patients achieving a Deauville score ≤4 proceeded to ASCT consolidation. After ASCT, patients received BV as maintenance for a total of 16 administrations. We collected data from 10 patients with a median age of 30.7 years. At a median follow-up of 16.5 months, we reported a complete metabolic remission (CMR) in eight patients (80%), with seven patients (70%) directly proceeding to ASCT (the other two patients in CMR are still undergoing treatment). BV consolidation was started in six patients and completed by three patients (one ongoing, two interruption). Two patients (20%) presented a progressive disease (PD) and subsequently died, while the others are still in CMR. The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients. [ABSTRACT FROM AUTHOR]

Simple Summary: As for many other cancers, the risk of developing hematologic malignancies increases considerably as people age. In recent years, a growing number of studies have highlighted the influence of the aging microenvironment on hematopoiesis and tumor progression. Mesenchymal stromal cells are a major player in intercellular communication inside the bone marrow microenvironment involved in hematopoiesis support. With aging, their functions may be altered, leading to hematopoiesis disturbances which can lead to hematologic cancers. A good understanding of the mechanisms involved in mesenchymal stem cell aging and the consequences on hematopoiesis and tumor progression is therefore necessary for a better comprehension of hematologic malignancies and for the development of therapeutic approaches. Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression. [ABSTRACT FROM AUTHOR]