Purpose of Review
Richter syndrome (RS) is an uncommon but aggressive evolution of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). RS is an unmet clinical need in the field of CLL. ...Recent advances in understanding the biology of this condition provide the rationale for testing new therapeutic concepts in order to improve the outcome of patients developing RS, which is so far poor. In this review, we summarize disease characteristics and available therapeutic options for RS.
Recent Findings
Current regimens with novel agents in monotherapy have shown little impact on survival. Nevertheless, the better reported outcome for RS has been achieved with the combination of chemo-immunotherapy with a novel agent, confirming the synergistic effect of the approaches. Still, the frailty of this population may impose a less toxic management leaving most patients with no reasonable therapeutic option.
Summary
Treatment options for RS need to be further expanded. Preclinical models in current development may allow to explore actionable pathways and identify new drug targeted combinations.
Richter transformation (RT), defined as the development of an aggressive lymphoma on a background of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), represents a clinical unmet ...need because of its dismal prognosis. An increasing body of knowledge in the field of RT is arising from the recent development of preclinical models depicting the biology underlying this aggressive disease. Consistently, new therapeutic strategies based on a genetic
are exploring actionable pathogenic pathways to improve the outcome of patients in this setting. In this review, we summarize the current understandings on RT biology and the available treatment options.
The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep ...next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy. ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA as an easily accessible source of tumor DNA for cHL genotyping. By identifying STAT6 as the most frequently mutated gene in ∼40% of cases, we refined the current knowledge of cHL genetics. Longitudinal ctDNA profiling identified treatment-dependent patterns of clonal evolution in patients relapsing after chemotherapy and patients maintained in partial remission under immunotherapy. By measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool to track residual disease that may integrate positron emission tomography imaging for the early identification of chemorefractory patients with cHL. Collectively, our results provide the proof of concept that ctDNA may serve as a novel precision medicine biomarker in cHL.
•ctDNA is as an easily accessible source of tumor DNA for cHL genotyping.•ctDNA is a radiation-free tool to track residual disease in cHL.
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The prognostic significance of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was identified when the biology of the disease was poorly understood and therapy was not effective. ...We assessed the clinical and biological significance of LDT in 848 CLL patients in a real-life setting and the context of new biomarkers and effective therapy. A short LDT (≤12 months) was enriched for adverse biomarkers. Patients with a rapid LDT did need therapy shortly after diagnosis (median 23 months vs. not reached; p < 0.001) and had a poorer overall survival (median 95 months vs. not reached p < 0.001). LDT, IGHV mutational status, Beta-2 microglobulin, and Rai clinical stage were independent predictors for time to first treatment in the whole series and in Binet stage A patients. No correlation was observed between LDT and response to chemoimmunotherapy. However, a short LDT along with age ≥65 years, high-risk FISH (del(17p), del(11q)), unmutated IGHV, increased Beta-2 microglobulin, and TP53 mutations predicted short survival. Moreover, the prognostic significance of LDT was independent of the CLL-IPI and the Barcelona/Brno prognostic model. LDT remains an important outcome marker in the modern CLL era and should be incorporated into the clinical assessment and stratification of CLL patients.
A systematic review of English and non-English articles using OVID MEDLINE (1980-2014) was performed to evaluate the potential value of prophylactic ligation of the thoracic duct in preventing ...chylous leakage after oesophagectomy for cancer. Search terms included Oesophagectomy OR esophagectomy AND chylothorax AND thoracic duct ligation. Only those papers that directly compared the incidence of chylothorax in patients who underwent prophylactic ligation ligation group (LG) with that in those who had conservative treatment were selected preservation group (PG); all the articles presenting original data and supplying sufficient information on the chylothorax rate after oesophagectomy were included. Independent extraction of articles was performed by two authors using predefined data fields, including study quality indicators. The PRISMA guidelines were carefully adhered to. A total of 5254 subjects were included in the 7 clinical studies examined into the current meta-analysis. Of these, 2179 patients underwent prophylactic ligature of the thoracic duct (LG group) and 3075 had preservation of the thoracic duct (PG group). A significant difference in terms of chylothorax rate odd ratios (ORs) 0.47 in favour of LG, 95% confidence interval (CI) 0.27-0.80 was noted between the LG group and the PG group. According to our meta-analysis and taking into account-specific caveats, prophylactic ligation of the thoracic duct could be considered as an effective preventative measure to reduce the incidence of postoperative chylothorax.
Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). These can be exacerbated by anti‐leukemic treatments. In addition, the typical patients ...with CLL already have fragilities and background risk factors that apply to the general population for severe COVID‐19. On these bases, patients with CLL may experience COVID‐19 morbidity and mortality. Recurrent seasonal epidemics of SARS‐CoV‐2 are expected, and doctors taking care of patients with CLL must be prepared for the possibility of substantial resurgences of infection and adapt their approach to CLL management accordingly. In this Guideline Article, we aim at providing clinicians with a literature‐informed expert opinion on the management of patients with CLL during SARS‐CoV‐2 epidemic.
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