Efficacité et tolérance du MabCampath® dans la LLC-B en phase précoce de rechute après autogreffe

Cette étude pilote a déterminé l'efficacité et la tolérance de l'anticorps monoclonal MabCampath® en phase précoce de rechute après autogreffe chez dix patients atteints de LLC-B. La durée du traitement a été de douze semaines, à raison de trois injections de 30 mg par semaine. Un taux de réponse objective de 75 % a été obtenu chez les huit patients évaluables, dont 50% de rémissions complètes et 25% de rémissions partielles. Sur les dix patients, six ont présenté une rémission phénotypique et moléculaire. La toxicité hématologique a été modérée, une neutropénie et une thrombopénie de grade III-IV selon la classification de l'OMS a été observée chez respectivement 20 et 50% des patients. 60% des patients ont présenté au moins un épisode fébrile, une seule infection de grade III-IV a été décrite. Le MabCampath® est apparu efficace et tolérable pour le traitement des rechutes après intensification thérapeutique par autogreffe.TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Antibody Responses after a Third Dose of COVID-19 Vaccine in Kidney Transplant Recipients and Patients Treated for Chronic Lymphocytic Leukemia

International audienceThe impact of a third dose of COVID-19 vaccine on antibody responses is unclear in immunocompromised patients. The objective of this retrospective study was to characterize antibody responses induced by a third dose of mRNA COVID-19 vaccine in 160 kidney transplant recipients and 20 patients treated for chronic lymphocytic leukemia (CLL). Prevalence of anti-spike IgG ≥ 7.1 and ≥ 30 BAU/mL after the third dose were 47% (75/160) and 39% (63/160) in kidney transplant recipients, and 57% (29/51) and 50% (10/20) in patients treated for CLL. Longitudinal follow-up identified a moderate increase in SARS-CoV-2 anti-spike IgG levels after a third dose of vaccine in kidney transplant recipients (0.19 vs. 5.28 BAU/mL, p = 0.03) and in patients treated for CLL (0.63 vs. 10.7 BAU/mL, p = 0.0002). This increase in IgG levels had a limited impact on prevalence of anti-spike IgG ≥ 30 BAU/mL in kidney transplant recipients (17%, 2/12 vs. 33%, 4/12, p = 0.64) and in patients treated for CLL (5%, 1/20 vs. 45%, 9/20, p = 0.008). These results highlight the need for vaccination of the general population and the importance of non-medical preventive measures to protect immunocompromised patients

Two cases of opportunistic parasite infections in patients receiving alemtuzumab

International audienceTwo cases are reported of rare digestive opportunistic parasites in patients being treated with alemtuzumab for lymphoid haematological malignancies. In both patients, classical biological examinations were insufficient to reach the diagnosis. Only specific parasitological techniques enabled diagnoses of cryptosporidiosis and microsporidiosis, respectively. In both cases, cellular immune reconstitution was sufficient to eradicate these opportunistic infections. In this context, parasitological diagnosis is often underestimated by medical practitioners, so immunologists and oncohaematologists need to be aware of this kind of opportunistic pathogen

Differential sensitization of cancer cells to doxorubicin by DHA: a role for lipoperoxidation.

Polyunsaturated fatty acids have been reported to enhance the cytotoxic activity of several anticancer drugs. In the present study, we observed that doxorubicin chemosensitization of breast cancer cell lines by docosahexaenoic acid (DHA, a long-chain omega-3 polyunsaturated fatty acid) was cell-line selective, affecting MDA-MB-231 and MCF-7 dox (a doxorubicin-resistant cell line) but not the parental MCF-7 cell line. DHA supplementation led to an increase in membrane phospholipid DHA level, but did not induce changes in intracellular [(14)C]doxorubicin accumulation. In MDA-MB-231, doxorubicin efficacy enhancement by DHA was linked to an increase in malondialdehyde level, a final product of lipid peroxidation. DHA elicited by itself a 3.7-fold malondialdehyde level increase, additive to that induced by doxorubicin. Addition of doxorubicin to DHA further increased the glutathione level, indicative of the generation of an oxidative stress. In contrast to MDA-MB-231, doxorubicin did not increase the malondialdehyde level in MCF-7, although DHA induced lipid peroxidation. Therefore in MCF-7, lipid peroxidation induced by DHA itself was not sufficient to trigger an oxidative stress and to subsequently increase sensitivity to doxorubicin. These data indicate that the differential effect of DHA among cells on drug toxicity results from a differential oxidative response to doxorubicin. Chemosensitization through fatty acids appears as a new promising adjuvant therapeutic paradigm, since omega-3 fatty acids are physiological molecules found in food and are nontoxic in vivo

Post-remission intervention with alemtuzumab or rituximab to eradicate minimal residual disease in chronic lymphocytic leukemia: where do we stand?

The introduction of purine nucleoside analogs, later in combination with alkylating moieties and anti-CD20 immunotherapy, has profoundly improved the response rate and response duration in patients with chronic lymphocytic leukemia (CLL). The quality of clinical response following treatment may be improved to a level where residual leukemic cells become undetectable. As patients with this type of response appear to have extended survival rates, minimal residual disease (MRD) eradication is considered a new objective in CLL treatment with the aim of improving progression-free survival (PFS) and potentially overall survival (OS). This review therefore aims to overview the prognostic value of MRD eradication in CLL, the role of post-remission intervention with "passive" immunotherapy (alemtuzumab or rituximab) so as to eliminate persistent MRD or prevent MRD relapse, the impact of these strategies on disease-free survival and their possible adverse consequences. The data indicate a potential for post-remission alemtuzumab or rituximab to prolong PFS in CLL, although more investigations and longer follow-up are required before MRD-guided strategies can be recommended outside of clinical trials

Pulmonary toxoplasmosis in immunocompromised patients with interstitial pneumonia: a single-centre prospective study assessing PCR-based diagnosis

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Real-world results of ibrutinib in relapsed/refractory CLL in France: Early results on a large series of 428 patients

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Response to rituximab in B-CLL patients is adversely impacted by frequency of IL-10 competent B cells and FcγRIIIa polymorphism. A study of FCGCLL/WM and GOELAMS groups

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