The off-line extracorporeal photopheresis (ECP) procedure requires photosensitization in an external cell therapy laboratory as per the French regulatory requirement. This regulation results in ...higher time and costs compared with the on-line alternative performed entirely at the patient's bedside. Recently, full in situ execution of the off-line procedure has been implemented in the Pitié-Salpêtrière Hospital Hemobiotherapy Department (Paris, France). This report summarizes the center's experience regarding the organizational and costs impacts of this change compared with the on-line procedure.
ECP was broken down into stages, and several procedures were monitored prospectively in real-life settings. The total costs associated with both procedures were the sum of the fixed costs and variable costs related to all stages of the procedures, nursing-time costs, property costs, and patient-related production loss costs.
Eight off-line ECP and fourteen on-line ECP procedures were monitored during five consecutive days. Procedure duration was not different (median 137.5 vs 154.0 minutes, P = .29). Times and costs associated with nursing were higher but offset by lower fixed costs of the off-line ECP. Total direct costs per procedure associated with using the off-line ECP were significantly lower than those of the on-line procedure (459.6 ± 7.1 EUR vs 953.8 ± 6.5 EUR; P = .0002). Similar results were observed when including the costs of patient production loss.
As a competitive time procedure, the in situ off-line method proved to be cost-efficient by effectively offering similar patient treatment per year compared with the on-line procedure.
Summary
Monoclonal immunoglobulin M (IgM) anti‐myelin‐associated glycoprotein (MAG) neuropathy is a rare disabling condition, most commonly treated with rituximab monotherapy (R), which leads to ...neurological improvement in only 30%–50% of patients. The combination of rituximab plus chemotherapy has been proven to improve the level of responses. We studied the outcomes of anti‐MAG neuropathy patients treated either by R, or by immunochemotherapy (ICT) in our centre, focusing on the incidence of the first neurological response evaluated by the modified Rankin scale (mRS). From 2011 to 2018, 64 patients were studied: 34 were treated with R and 30 with ICT. According to our treatment decision‐making process, the median mRS was higher in the ICT group (mRS 2) than in the R group (mRS 1). At one year, improvements of the mRS rates were 46% and 18% in the ICT and R groups of patients respectively, with median times to response of eight and 13 months (p = 0.023). Adverse effects were higher in the ICT group: 62% vs 15% (p ˂ 0.01), all grades included. One secondary acute leukaemia occurred five years after treatment with ICT. In conclusion, ICT may be used as a valid option for patients with rapidly progressive and/or severe anti‐MAG neuropathy symptoms.
EBV‐positive and EBV‐negative posttransplant lymphoproliferative disorders (PTLDs) arise in different immunovirological contexts and might have distinct pathophysiologies. To examine this hypothesis, ...we conducted a multicentric prospective study with 56 EBV‐positive and 39 EBV‐negative PTLD patients of the K‐VIROGREF cohort, recruited at PTLD diagnosis and before treatment (2013–2019), and compared them to PTLD‐free Transplant Controls (TC, n = 21). We measured absolute lymphocyte counts (n = 108), analyzed NK‐ and T cell phenotypes (n = 49 and 94), and performed EBV‐specific functional assays (n = 16 and 42) by multiparameter flow cytometry and ELISpot‐IFNγ assays (n = 50). EBV‐negative PTLD patients, NK cells overexpressed Tim‐3; the 2‐year progression‐free survival (PFS) was poorer in patients with a CD4 lymphopenia (CD4+<300 cells/mm3, p < .001). EBV‐positive PTLD patients presented a profound NK‐cell lymphopenia (median = 60 cells/mm3) and a high proportion of NK cells expressing PD‐1 (vs. TC, p = .029) and apoptosis markers (vs. TC, p < .001). EBV‐specific T cells of EBV‐positive PTLD patients circulated in low proportions, showed immune exhaustion (p = .013 vs. TC) and poorly recognized the N‐terminal portion of EBNA‐3A viral protein. Altogether, this broad comparison of EBV‐positive and EBV‐negative PTLDs highlight distinct patterns of immunopathological mechanisms between these two diseases and provide new clues for immunotherapeutic strategies and PTLD prognosis.
This broad comparison of T cell and NK cell characteristics between EBV‐positive and EBV‐negative PTLDs highlight distinct patterns of immunopathological mechanisms and provide new clues for prospective surveillance and immunotherapeutic strategies.
Posaconazole is a triazole antifungal used to prevent invasive fungal infections (IFIs) in patients receiving chemotherapy or haemotopoietic stem cell transplantation. Due to highly variable ...bioavailability of the oral suspension formulation, a delayed-release tablet was developed which showed improved bioavailability. A minimal target posaconazole plasma concentration of 0.7 mg/L is recommended for prophylaxis of IFIs. However, the relationship between plasma concentration of posaconazole and its efficacy against IFIs remains unclear. We analysed trough posaconazole concentrations and response against IFIs in 50 and 104 patients with haematologic malignancies receiving prophylactic posaconazole as the tablet or suspension formulation, respectively. Mean plasma concentration of posaconazole was 1.91 ± 1.06 mg/L and 0.82 ± 0.57 mg/L in the tablet and the oral suspension group, respectively (p < 0.0001). The percentage of patients reaching the minimal target concentration of 0.7 mg/L was 92.0% and 47.1% in the tablet and oral suspension groups, respectively (p < 0.0001). Emergent aspergillosis occurred in 9 (8.7%) patients in the suspension group and in none of the patients taking the tablet formulation (p = 0.032). Our results show a relationship between plasma concentrations of posaconazole and its prophylactic efficacy in patients with haematologic malignancies. Target posaconazole concentrations are reached more efficiently with the tablet than with the suspension formulation.
Central nervous system involvement by malignant cells is a rare complication of Waldenström macroglobulinemia, and this clinicopathological entity is referred to as the Bing-Neel syndrome. There is ...currently no consensus on the diagnostic criteria, therapeutic approaches and response evaluation for this syndrome. In this series, we retrospectively analyzed 44 French patients with Bing-Neel syndrome. Bing-Neel syndrome was the first manifestation of Waldenström macroglobulinemia in 36% of patients. When Waldenström macroglobulinemia was diagnosed prior to Bing-Neel syndrome, the median time interval between this diagnosis and the onset of Bing-Neel syndrome was 8.9 years. This study highlights the possibility of the occurrence of Bing-Neel syndrome without any other evidence of progression of Waldenström macroglobulinemia. The clinical presentation was heterogeneous without any specific signs or symptoms. Biologically, the median lymphocyte count in the cerebrospinal fluid was 31/mm(3). Magnetic resonance imaging revealed abnormalities in 78% of the cases. The overall response rate after first-line treatment was 70%, and the overall survival rate after the diagnosis of Bing-Neel syndrome was 71% at 5 years. Altogether, these results suggest that Bing-Neel syndrome should be considered in the context of any unexplained neurological symptoms associated with Waldenström macroglobulinemia. The diagnostic approach should be based on cerebrospinal fluid analysis and magnetic resonance imaging of the brain and spinal axis. It still remains difficult to establish treatment recommendations or prognostic factors in the absence of large-scale, prospective, observational studies.
The bendamustine-rituximab (BR) schedule is an efficient first-line therapy in Waldenström macroglobulinaemia (WM). A previous analysis of 69 patients who received this treatment confirmed a high ...response rate and good progression-free (PFS) and overall survival (OS). With a median follow-up of 76.1 months (95% confidence interval CI 69.9-80.6), 5-year outcome is still excellent at 66.63% (95% CI 56.09-79.17) for PFS and 80.01% (95% CI 70.82-90.41) for OS. The rate of secondary cancers is 17.66% (IQR 7.99-27.64) at 66 months. Relapsed patients who received ibrutinib as second-line clearly benefited from this schedule. This confirms current recommendations suggesting BR long-term efficacy as first-line option in WM.
Background
Cancer patients may be at higher risk for severe coronavirus infectious disease-19 (COVID-19); however, the outcome of Primary Central Nervous System Lymphoma (PCNSL) patients with ...SARS-CoV-2 infection has not been described yet.
Methods
We conducted a retrospective study within the
Lymphomes Oculo-Cérébraux
national network (LOC) to assess the clinical characteristics and outcome of SARS-CoV-2 infection in PCNSL patients (positive real-time polymerase chain reaction of nasopharyngeal swab or evocative lung computed tomography scan). We compared clinical characteristics between patients with severe (death and/or intensive care unit admission) and mild disease.
Results
Between March and May 2020, 13 PCNSL patients were diagnosed with SARS-CoV-2 infection, 11 (85%) of whom were undergoing chemotherapy at the time of infection. The mortality rate was 23% (3/13), and two additional patients (15%) required mechanical ventilation. Two patients (15%) had no COVID-19 symptoms. History of diabetes mellitus was more common in severe patients (3/5 vs 0/8,
p
= 0.03). Two patients recovered from COVID-19 after mechanical ventilation during more than two weeks and resumed chemotherapy. In all, chemotherapy was resumed after COVID-19 recovery in nine patients (69%) after a median delay of 16 days (range 3–32), none of whom developed unusual chemotherapy complication nor SARS-Cov2 reactivation.
Conclusion
This preliminary analysis suggests that, while being at higher risk be for severe illness, PCNSL patients with COVID-19 might be treated maximally especially if they achieved oncological response at the time of SARS-CoV-2 infection. Chemotherapy might be resumed without prolonged delay in PCNSL patients with COVID-19.
Type I cryoglobulinemia vasculitis (CryoVas) is considered a life-threatening condition; however, data on the characteristics and outcome are scarce. To analyze the presentation, prognosis, and ...efficacy and safety of treatments of type I CryoVas, we conducted a French nationwide survey that included 64 patients with type I CryoVas between January 1995 and July 2010: 28 patients with monoclonal gammopathy of unknown significance (MGUS) and 36 with hematologic malignancy.Type I monoclonal CryoVas was characterized by severe cutaneous involvement (necrosis and ulcers) in almost half the patients and high serum cryoglobulin levels, contrasting with a lower frequency of glomerulonephritis than expected. The 1-, 3-, 5-, and 10-year survival rates were 97%, 94%, 94%, and 87%, respectively. Compared to MGUS, type I CryoVas related to hematologic malignancy tended to be associated with a poorer prognosis. Therapeutic regimens based on alkylating agents, rituximab, thalidomide or lenalinomide, and bortezomib showed similar efficacy on vasculitis manifestations, with clinical response rates from 80% to 86%.Data from the CryoVas survey show that the prognosis of type I CryoVas does not seem to be as poor as previously suggested. Besides alkylating agents, the use of regimens based on rituximab, thalidomide or lenalinomide, and bortezomib are interesting alternative options, although the exact role of each strategy remains to be defined.
Summary
Paraproteinaemic neuropathies are a heterogeneous group of disorders most frequently associated with IgM monoclonal gammopathies including Waldenström macroglobulinaemia (WM). Their ...consequences are significant for affected patients, and their management challenging for their physicians. The variability in clinical presentation and time course hamper classification and management. The indications for invasive investigations such as cerebrospinal fluid analysis, nerve conduction tests and sensory nerve biopsies are unclear, and the optimum way to measure clinical response to treatment unknown. When to intervene and and how to treat, also present challenges to physicians. As part of its latest deliberations at the International Workshops on WM (IWWM) in London, UK (August 2014), the IWWM8 panel have proposed a consensus approach to the diagnosis and management of peripheral neuropathies associated with IgM monoclonal gammopathies, including WM. Importantly, a consensus regarding the use of clinical outcome measures and recommended models of care for this group of patients is discussed, as well as appropriate treatment interventions.
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