Another treatment option for relapsed or refractory chronic lymphocytic leukaemia.

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

Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Management of craniofacial development in the Parry-Romberg syndrome: Report of two patients

Objective: The aim of this article is to describe the orthodontic therapy for Parry-Romberg syndrome. The therapeutic goal is to minimize the wasting effects of progressive atrophy on facial development of a part of the face. Design: To correct problems affecting craniofacial development of these patients, occurring during puberty, an orthodontic appliance was employed, which helps maintain parallelism of the facial planes, in particular the mandibular plane. Setting: Orthodontic care was carried out in the Dental Clinic of the Catholic University of the Sacred Heart of Rome. Intervention: Two patients underwent orthodontic therapy for 6 years. Appliances were checked every month and modified periodically so as to adapt to facial bone growth. Results: At the end of craniofacial growth, the mandible was almost symmetric and the problem relating to atrophy remained confined to the initial area. Cephalometric analyses demonstrated that the occlusal plane and the mandibular plane maintained a straight orientation in relation to the bizygomatic plane. The ratio between the left and right side of the ramus and condyle, in the mandible, improved. Conclusions: The use of orthodontic therapy allows patients affected by hemifacial progressive atrophy to present a more harmonic face at the end of puberty when final reconstruction can be planned. These results provide for a limitation of surgical intervention to the sclerodermic area alone

Sense or sensibility? The neuro-functional basis of the structural matching effect in persuasion

The present study investigates the neural pathways underlying individual susceptibility to affective or cognitive information in persuasive communication, also known as the structural matching effect. Expanding on the presumed involvement of the ventromedial prefrontal cortex (vMPFC) in persuasion, we hypothesized that the vMPFC contributes to the evaluation of persuasive information depending on its match with the recipient’s affective or cognitive predominance. During functional magnetic resonance imaging, 30 participants evaluated 10 consumable products presented with both affective and cognitive persuasive messages. All participants were characterized on a continuum regarding their personal orientation in terms of individual differences in need for affect (NFA) and need for cognition (NFC). The results showed that the vMPFC, posterior cingulate cortex, and cerebellum are more strongly activated when the persuasive message content, either affective or cognitive, matched the recipient’s individual affective or cognitive orientation. Interestingly, this effect in the vMPFC was found specifically when participants evaluated the products presented by the persuasive messages, whereas the correlation in the posterior cingulate cortex and cerebellum activity was detected when reading the messages. These results confirm the hypothesis that the vMPFC plays a role in subjectively weighting persuasive message content depending on individual differences in affective and cognitive orientation. Such a structural matching effect might involve the vMPFC particularly during explicit expressions of subjective valuations. These novel findings also further develop the conceptualisation of the role of the vMPFC in self-related processing

Management of elderly and unfit patients with chronic lymphocytic leukemia

Introduction: 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

Clinical characteristics and outcome of patients with autoimmune hemolytic anemia (AIHA) uniformly defined as primary by a diagnostic work-up

Primary autoimmune hemolytic anemia (P-AIHA) is a relatively uncommon and hetereogeneous disease characterized by the destruction of red blood cells due to anti-erythrocyte autoantibodies (AeAbs) in the absence of an associated disease [1–3]. Secondary AHIA is frequently associated with lymphoproliferative diseases (LD) in particular, chronic lymphocytic leukemia, aggressive or indolent lymphomas, autoimmune disorders, malignancies other than lymphoid, and infections [1,2,4]. On the hypothetical assumption that in a significant proportion of cases defined as P-AIHA the clinical heterogeneity could be due to an ignored associated disease, we retrospectively analyzed the clinical characteristics and outcome of patients with a diagnosis of P-AIHA based on a diagnostic work-up aimed at excluding or identifying an associated disease. ..

Continous Treatment with Ibrutinib in 100 Untreated Patients with TP53 Disrupted Chronic Lymphocytic Leukemia. A Real-Life Campus CLL Study

Continous Treatment with Ibrutinib in 100 Untreated Patients with TP53 Disrupted Chronic Lymphocytic Leukemia. A Real-Life Campus CLL Stud

Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study

Chronic lymphocytic leukemia (CLL) therapies differ in efficacy, side effects, route, frequency, and duration of administration. We assessed patient preferences for treatment attributes and evaluated associations with disease stage, treatment line, and socio-demographic characteristics in a cross sectional, observational study conducted at 16 Italian hematology centers. Study visits occurred between February and July 2020; 401 adult patients with CLL (201 Watch and Wait (W & W), 200 treated) participated in a discrete choice experiment (DCE), composed of 8 choices between pairs of treatment profiles with different levels of 5 attributes of currently available CLL treatments (length of response, route and duration of administration, risk of side effects including diarrhea, infections, or organ damage). Health-related quality of life was assessed with the EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16. Previously treated patients had longer disease duration (7 vs. 5 years), higher prevalence of serious comorbidities (45.5% vs. 36.2%) and high-risk molecular markers (unmutated IGHV 55.6% vs. 17.1%; TP53 mutation 15.2% vs. 4.0%). Health-related quality of life scores were similar between groups. In the DCE, W & W patients rated "possible occurrence of infections" highest (relative importance [RI] = 36.2%), followed by "treatment and relevant duration" (RI = 28.0%) and "progression-free survival (PFS)" (RI = 16.9%). Previously treated patients rated "treatment and relevant duration" highest (RI = 33.3%), followed by "possible occurrence of infections" (RI = 28.8%), "possible occurrence of organ damage" (RI = 19.4%), and "PFS" (RI = 9.8%). Concern over infection was rated highest overall; unexpectedly PFS was not among the most important criteria in either group, suggesting that the first COVID-19 pandemic wave may have influenced patient preferences and concerns about CLL therapy options