We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%. Prior treatment for CLL had been received by 82% of patients and included fludarabine in 67%. Coexistence of CLL and HL was detected in the same bioptic tissue in 87% of cases. The most common administered treatment was the ABVD regimen given to 22 patients (66.6%). The complete response (CR) rate after ABVD was 68%, and was influenced by the IPS (P = .03) and interval from the last CLL treatment (P = .057). Survival from HL was also influenced by the IPS (P = .006) and time from the last CLL treatment (P = .047). The achievement of CR with ABVD was the only significant and independent factor predicting survival (P = .037). Taken together, our results show that the IPS and the interval from the prior CLL treatment influence the likelihood of achieving CR after ABVD, which is the most important factor predicting survival of patients with CLL developing HL.
The authors present a case report of a 60-year-old man with a hepatic unknown mass. For diagnosis, they used ECO, CT (with and without contrast), MR (with and without contrast) and an ultrasound-assisted percutaneous lesion biopsy. Thus the mass-lesion in the liver appeared to be an intrahepatic accessory spleen in a patient afflicted with chronic hepatitis.
About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL. The most frequently observed age-related toxicities, fitness assessments, supportive care measures and treatment options for elderly patients and for patients who are deemed unfit will be discussed. Literature search methodology included examination of PubMed index. Expert commentary: During the last decade, different trials focusing on elderly/unfit patients have investigated more tolerable chemoimmunotherapy schedules and, more recently, the activity and safety of chemo-free regimens. Chlorambucil combined with an anti-CD20 monoclonal antibody has shown clinical activity with a relatively good profile of toxicity. The recent introduction of the B-cell receptor antagonists, ibrutinib and idelalisib, and other targeted drugs in development (e.g. venetoclax), is broadening the therapeutic armamentarium of elderly CLL patients.
P525L Fused-in-Sarcoma (FUS) mutation is associated with a specific amyotrophic lateral sclerosis (ALS) phenotype characterized by a juvenile-onset and a severe course. 1 This harmful point mutation is located in the nuclear localization signal (NLS) domain at the protein C-terminal. 2 Although wild-type FUS protein is expressed almost exclusively in the nucleus, the P525L FUS mutation leads to a protein mislocalization into the cytoplasm 3,4 because of its loss of capacity to bind its transporter karyopherin-2 and to be transferred back to the nucleus. 3 Here, we compare FUS expression and localization in skin fibroblasts of 2 sisters, both carriers of a P525L FUS mutation, belonging to a Sicilian family with this mutation. 4,5The first sister (DC) was seen at age 21 years when she was asymptomatic. After almost 2-year follow-up, she developed a bulbar form of ALS and died 13 months after disease onset. In both conditions, i.e., asymptomatic (DC-A, at the time of the first visit) and symptomatic (DC-S, soon after disease onset), skin fibroblasts were purified and cultured. The other sister (DL) was seen when she was aged 25 years; on that occasion, fibroblasts were also purified. She is at present asymptomatic.We studied the expression and subcellular localization of FUS protein in fibroblasts from the 2 P525L FUS carriers. Concerning DC, we analyzed FUS expression in the fibroblasts when she was asymptomatic and after the disease onset. A patient with sporadic clinically definite ALS with no known ALS-related gene mutations (sporadic ALS [S-ALS]) and a healthy control (HC) were used as controls.All individuals and patients involved in this study signed informed consent for the genetic testing and the skin biopsy. The experimental protocol was approved by the Ethics Committee Palermo 1 (July 2017).Fibroblasts were cultured in Dulbecco's Modified Eagle Medium supplemented with 10% calf serum and antibiotic/antimycotic solution. Cells were plated on glass coverslips to perform immunofluorescence by using a polyclonal FUS antibody (11570-1-AP, Proteintech Group, Chicago, IL). The analysis of subcellular FUS expression was made through a Zeiss LSM5 confocal microscope. Cell counting for subcellular FUS expression was performed as described by Lo Bello et al. 4 As expected, FUS mislocalized to the cytoplasm in almost all fibroblasts carrying the P525L FUS mutation. 4 Conversely, control fibroblasts (S-ALS and HC) expressed FUS only in the nucleus (figure, A).After a more careful inspection, we observed important differences in the nucleuscytoplasm distribution of FUS protein between the 2 FUS mutants (DC and DL). By visual
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