Targeting TP53 disruption in chronic lymphocytic leukemia: Current strategies and future directions.

In the modern era of Chronic Lymphocytic Leukemia (CLL) targeted therapy, the loss of p53 function due to genetic abnormalities remains a significant challenge. This is because even targeted agents, which are currently the mainstay of treatment for CLL, do not directly target p53 or restore its disrupted pathway. Consequently, resistance to therapy and unfavorable clinical outcomes often accompany these p53-related abnormalities.

Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option.

Ibrutinib, the first-in-class Bruton's tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed/refractory (R/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site.

Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia.

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission.

Current perspectives regarding SARS-CoV-2 vaccination in chronic lymphocytic leukemia.

In immunocompetent people, the mRNA vaccines BNT162b2 and mRNA-1273 have been shown to be safe and effective against coronavirus disease of 2019 (COVID-19). However, results of cohort studies and meta-analyses have indicated that the degree of humoral response to SARS-CoV-2 vaccines in patients with chronic lymphocytic leukemia (CLL) appears to be lower than that observed in the general population. These inadequate responses are mainly related to the disease itself and to the immunosuppressive effect of therapies administered.

A perspective on prognostic models in chronic lymphocytic leukemia in the era of targeted agents.

Despite the increase in the number of prognostic models currently available for evaluating patients with chronic lymphocytic leukemia (CLL), their current application and utilization in clinical practice in the era of targeted agents is unclear. A critical reappraisal of recently developed prognostic models is presented in this review. The underlying CLL's genetic instability and changes in the host's health and comorbidities can all contribute to the acquisition of additional risk factors for adverse outcomes during the course of the disease.

Hairy cell leukemia and COVID-19 adaptation of treatment guidelines.

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients.

Current and emerging investigational venetoclax-based therapies in chronic lymphocytic leukemia.

: Venetoclax has emerged as a breakthrough treatment which has revolutionized the therapeutic paradigm of chronic lymphocytic leukemia (CLL). This is primarily attributed to the efficacy of venetoclax as a time-limited, chemo-free, therapy in a field dominated by targeted agents given on a continuous schedule. Furthermore, compelling clinical data support the use of venetoclax in combination with other targeted agents in the hope of preventing drug resistance due to the emergence of acquired mutations.

Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases.

Objectives: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only.

Methods: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study.

Results: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.

Chronic lymphoproliferative disorders and secondary cancers in the era of purine analogues and beyond.

The low grade chronic lymphoproliferative disorders include chronic lymphocytic leukemia, Waldenstroms macroglobulinemia, follicular lymphoma and hairy cell leukemia. Traditionally considered incurable, these disorders have been associated with a risk of haematological and solid organ malignancies secondary to both the underlying disease and the associated treatment. The introduction of purine analogues into treatment paradigms has seen increased rates of therapy related myelodysplasia reported and it remains unclear yet on the impact the targeted novel therapies play in the development of secondary cancers.

Demyelinating brain lesions developing in a patient with chronic lymphocytic leukemia shortly after treatment with a fludarabine containing regimen.

Autoimmune manifestations are known to occur in patients with chronic lymphocytic leukemia (CLL) and of these hemolytic anemia and immune thrombocytopenia are the most well recognized. Autoimmunity may also be triggered by some of the therapeutic agents used like purine analoges and these events may sometimes be severe and even fatal. Non-hematological autoimmune stigmata occur far less frequently and are rarely encountered.

Bone lesions in hairy cell leukemia: Diagnosis and treatment.

Skeletal involvement is a rare complication of hairy cell leukemia (HCL) with an incidence of approximately 3%. Bone lesions are commonly lytic, and the most common sites of involvement are the femoral head and neck. Skeletal involvement is typically associated with high tumor burden and bone marrow infiltration.

Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma.

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%.

Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group.

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone.