Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
Transplant‐ineligible relapsed/refractory (rr) diffuse large B‐cell lymphoma (DLBCL) patients represent an unmet medical need. Polatuzumab vedotin (Pola), an anti‐CD79b antibody‐drug‐conjugate (ADG), with bendamustine‐ rituximab(BR) has recently gained approval for these patients, both in the USA and Europe, based on the GO29365 phase IIb trial. Real‐life data with Pola are extremely limited. We report the outcomes of 61 Greek patients, who received Pola‐(B)R mainly within a compassionate use program. Treatment was given for up to six 21‐day cycles. Bendamustine was omitted in three cases due to previous short‐lived responses. Fourty‐nine rrDLBCL(efficacy cohort‐EC) and 58 rr aggressive B‐NHL (safety cohort‐SC) patients received at least 1 Pola‐BR cycle. Twenty‐one (43%) patients of the EC responded with 12/49 (25%) CR and 9/49 (18%) PR as best response. Median progression–free survival, overall survival and duration of response were 4.0, 8.5, and 8.5 months respectively, while 55% of patients experienced a grade ≥3 adverse event, mainly hematologic. Treatment discontinuations and death during treatment were mainly due to disease progression. Twenty‐two (41%) patients received further treatment; 11/22 are still alive, including one after CAR‐T cells, and two after stem cell transplantation. Our data confirm that Pola‐BR is a promising treatment for rrDLBCL patients, inducing an adequate response rate with acceptable toxicity. Pola‐BR could be used as bridging therapy before further consolidative treatments.
Blood circulating endothelial cells (CECs), with their resting and activated subsets, (rCECs and aCECs) and circulating progenitors cells (CEPs) are two extremely rare cell populations that are important in tissue vascularization. Their number and function are modulated in diseases involving vascular injury, such as human tumours. Although a consensus on the phenotypic definition of endothelial cells, as well as on the optimal enumeration technique, is still lacking, the number of clinical studies based on assessment of these cells is rapidly expanding, as well as the analytical methods employed. The present study aimed to develop a rapid and sensitive flow cytometric method of quantifying and characterizing CECs (with both their subsets and the apoptotic fraction) and CEPs. We analysed peripheral blood samples from 21 subjects with a six-colour flow cytometric approach allowing detection of the cell phenotype of CECs and CEPs using a monoclonal antibodies panel and a dedicated gating strategy. Apoptotic CECs were detected with Annexin V and dead cells with 7-amino-actinomycin D staining. The described technique proved to be a new, reliable, tool increasing our knowledge of the biology of CECs and CEPs and can readily be applied in the study of many pathological conditions characterized by endothelial damage.
The involvement of the central nervous system (CNS) in Waldenström’s Macroglobulinemia (WM) is a rare extramedullary manifestation of the disease known as Bing-Neel syndrome (BNS). To expand our understanding of this disease manifestation, we conducted a retrospective analysis of the incidence of BNS in 86 consecutive patients with WM [70% male, median age 65 years (range 33-86)] seen in our center during a 30-year period. Six patients (7%) from this group were diagnosed with BNS. The median period of time between WM diagnosis and BNS diagnosis was 6.8 years (range 2.3-15). They demonstrated a range of neurological deficits, including transient expressive aphasia, impaired vision, resting hand tremor, foot drop, and headache. Between the onset of symptoms and the diagnosis of BNS, the median time interval was 12.5 months (range 1-30). The diagnosis was made not on the basis of neurological symptoms or radiological evidence, but on the basis of the presence of WM cells in cerebrospinal fluid (CSF). Intrathecal chemotherapy with methotrexate, cytarabine, and dexamethasone (IT MTX, ARA-C, DEX) was used as front-line treatment, followed by intensive immunochemotherapy with rituximab, high-dose MTX, and ARA-C (R-Hi MTX/ARA-C) in three patients who were fit enough to receive this type of cytotoxic regimen, and rituximab plus bendamustine (R-Benda) in two patients who simultaneously required treatment for WM. Ibrutinib was administered to five patients (three as consolidation and two for initial treatment). All patients responded to front-line treatment, with four (67%) achieving partial response (PR) and two (33%) achieving complete response (CR). This study provides insight into the clinical presentation, diagnostic and treatment options, as well as the outcome of patients who have BNS.
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