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BackgroundDonor specific antibodies (DSAs) can be responsible for graft failure (GF) in the setting of mismatched hematopoietic stem cell transplantation (HSCT). The aim of our study is to report the experience of the Madrid Group of Hematopoietic Transplant (GMTH) in patients with DSAs undergoing haplo-HSCT.MethodsPatients undergoing haplo-HSCT in centers from the GMTH from 2012 to 2020 were included in the study. DSAs were analyzed with a solid-phase single-antigen immunoassay; monitoring was performed during desensitization on days -14, -7, 0 and in a weekly basis until neutrophil engraftment. Desensitization strategies varied depending on center experience, immunofluorescence intensity, complement fixation and type of antibodies.ResultsWe identified a total of 20 haplo-HSCT in 19 patients performed with DSAs in 5 centers. 10 (53%) patients presented anti-HLA class I DSAs (6 of them with > 5000 mean fluorescence intensity (MFI)), 4 (21%) presented anti-HLA class II (1 with > 5000 MFI) and 5 (26%) presented both anti-HLA class I and II (5 with > 5000 MFI). 90% of patients received at least two treatments as desensitization strategy and all experienced a decrease of MFI after desensitization (mean reduction 74%). Only one patient who developed progressive increase of MFI after infusion developed GF. Desensitization treatments used included rituximab, immunoglobulins, therapeutic plasma exchange, incompatible platelets, buffy coat and immunosuppressors. Seventeen (90%) patients achieved neutrophil engraftment; one patient died before engraftment because of infection and one patient with class I DSAs developed primary GF despite an intensive desensitization. After a median follow-up of 10 months, OS and EFS were 60% and 58%, respectively, cumulative incidence of relapse was 5% and NRM was 32%.ConclusionsDespite the optimal strategy of DSAs desensitization remains unclear, the use of desensitization treatment guided by DSAs intensity kinetics constitute an effective approach with high rates of engraftment for patients with DSAs in need for an haplo-HSCT lacking an alternative suitable donor.

Background: Donor specific antibodies (DSAs) can be responsible for graft failure (GF) in the setting of mismatched hematopoietic stem cell transplantation (HSCT). The aim of our study is to report the experience of the Madrid Group of Hematopoietic Transplant (GMTH) in patients with DSAs undergoing haplo-HSCT. Methods: Patients undergoing haplo-HSCT in centers from the GMTH from 2012 to 2020 were included in the study. DSAs were analyzed with a solid-phase single-antigen immunoassay; monitoring was performed during desensitization on days -14, -7, 0 and in a weekly basis until neutrophil engraftment. Desensitization strategies varied depending on center experience, immunofluorescence intensity, complement fixation and type of antibodies. Results: We identified a total of 20 haplo-HSCT in 19 patients performed with DSAs in 5 centers. 10 (53%) patients presented anti-HLA class I DSAs (6 of them with > 5000 mean fluorescence intensity (MFI)), 4 (21%) presented anti-HLA class II (1 with > 5000 MFI) and 5 (26%) presented both anti-HLA class I and II (5 with > 5000 MFI). 90% of patients received at least two treatments as desensitization strategy and all experienced a decrease of MFI after desensitization (mean reduction 74%). Only one patient who developed progressive increase of MFI after infusion developed GF. Desensitization treatments used included rituximab, immunoglobulins, therapeutic plasma exchange, incompatible platelets, buffy coat and immunosuppressors. Seventeen (90%) patients achieved neutrophil engraftment; one patient died before engraftment because of infection and one patient with class I DSAs developed primary GF despite an intensive desensitization. After a median follow-up of 10 months, OS and EFS were 60% and 58%, respectively, cumulative incidence of relapse was 5% and NRM was 32%. Conclusions: Despite the optimal strategy of DSAs desensitization remains unclear, the use of desensitization treatment guided by DSAs intensity kinetics constitute an effective approach with high rates of engraftment for patients with DSAs in need for an haplo-HSCT lacking an alternative suitable donor. [ABSTRACT FROM AUTHOR]

Résumé Les allo-immunisations anti-HLA sont à l’origine de complications cliniques en transfusion et en transplantation d’organe solide. Le développement des nouveaux tests de recherche et d’identification des anticorps anti-HLA en phase solide particulièrement ceux utilisant la technique Luminex ® a complètement révolutionné le suivi de l’allo-immunisation anti-HLA du fait de leur extrême sensibilité. Ils permettent de mieux caractériser ces anticorps, d’identifier des antigènes permis et de réaliser des cross-matches virtuels ce qui participe incontestablement à l’amélioration de la prise en charge des patients transfusés et des patients en attente de greffe ou greffés. Néanmoins cette nouvelle technologie présente des limites qu’il convient de bien connaître pour en faire bon usage. Les techniques de cross-matches cellulaires basées sur la lymphocytotoxicité (LCT) et la cytométrie en flux (CMF) continuent malgré tout à être utilisées en transplantation d’organe. Les différences de sensibilité observées entre ces techniques posent de nouveaux problèmes d’interprétation et de prise de décision quant à la conduite à tenir chez ces patients. Allo-immunizations against HLA antigens are known to be deleterious in transfusion and organ transplantation. The development of new tests based on solid phase assays for screening and identification of HLA antibodies in particular those using Luminex ® bead based technology has completely changed the way of allo-immunization monitoring because of their extreme sensitivity. They allow a better characterization of these antibodies, identification of acceptable antigens and the use of virtual cross-matches. All these new possibilities improve the managing of patients before and after platelets transfusion or organ transplantation. However, this technology displays some limits that should be known in order to interpret correctly the results. Beside these bead based assays, cellular cross-matches based on Complement Dependent Cytotoxicity (CDC) and flow cytometry are still used and useful in organ transplantation since beads are produced in vitro and do not reflected exactly what happens physiologically. Moreover, differences of sensitivity between these methods make results interpretation and decision making difficult in some cases. [ABSTRACT FROM AUTHOR]

Influenza hemagglutination inhibition (HI) and virus microneutralization assays (MN) are widely used for seroprevalence studies. However, these assays have limited field portability and are difficult to fully automate for high throughput laboratory testing. To address these issues, three multiplex influenza subtype-specific antibody detection assays were developed using recombinant hemagglutinin antigens in combination with Chembio, Luminex ® , and ForteBio ® platforms. Assay sensitivity, specificity, and subtype cross-reactivity were evaluated using a panel of well characterized human sera. Compared to the traditional HI, assay sensitivity ranged from 87% to 92% and assay specificity in sera collected from unexposed persons ranged from 65% to 100% across the platforms. High assay specificity (86–100%) for A(H5N1) rHA was achieved for sera from exposed or unexposed to hetorosubtype influenza HAs. In contrast, assay specificity for A(H1N1)pdm09 rHA using sera collected from A/Vietnam/1204/2004 (H5N1) vaccinees in 2008 was low (22–30%) in all platforms. Although cross-reactivity against rHA subtype proteins was observed in each assay platform, the correct subtype specific responses were identified 78%–94% of the time when paired samples were available for analysis. These results show that high throughput and portable multiplex assays that incorporate rHA can be used to identify influenza subtype specific infections. [ABSTRACT FROM AUTHOR]

Résumé Chez les patients présentant des besoins transfusionnels plaquettaires importants et récurrents, la survenue d’un état réfractaire à la transfusion plaquettaire est un enjeu majeur. Les causes en sont multiples, qu’elles soient non immunologiques ou immunologiques. Les conflits allo-immuns en transfusion plaquettaire impliquent fréquemment les antigènes du complexe majeur d’histocompatibilité, en particulier les molécules HLA de classe I (Human Leucoyte Antigen), et dans une moindre mesure les antigènes spécifiquement plaquettaires (HPA Human Platelet Antigen). Les principales causes d’allo-immunisation sont la grossesse, la transplantation d’organe ou même les transfusions, bien que la déleucocytation ait considérablement diminué la fréquence d’allo-immunisation directe post-transfusionnelle. Après transfusion, la fixation des allo-anticorps sur les antigènes plaquettaires incompatibles conduit à une destruction accélérée par la rate des plaquettes transfusées. Ces dernières années, des technologies innovantes ont été développées pour le diagnostic de ces allo-immunisations, à la fois plus sensibles et plus spécifiques tel que la technique LUMINEX ® . La connaissance des avantages mais également des limites de chaque test est essentielle pour la mise en œuvre de nouvelles stratégies diagnostiques pour une meilleure prévention et prise en charge des inefficacités transfusionnelles plaquettaires, incluant une réponse adaptée en fonction du contexte du patient. Ces tests permettent une sélection de concentrés plaquettaires HLA ou HPA identiques ou compatibles à partir du profil immunologique du patient ou d’une analyse épitopique HLA. Des études prospectives doivent être menées pour confirmer le bénéfice apporté par ces nouvelles technologies et l’harmonisation des stratégies de prise en charge des conflits allo-immuns en transfusionnelle plaquettaire. Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens. After transfusion, platelet count is decreased by accelerated platelet destruction related to antibodies fixation on incompatible platelet antigens. New laboratory tests for allo-antibodies identification were developed to improve sensibility and specificity, especially with the LUMINEX ® technology. The good use and interpretation of these antibodies assays can improve strategies for platelet refractoriness prevention and management with a patient adapted response. Compatible platelets units can be selected according to their identity with recipient typing or immune compatibility regarding HLA or HPA antibodies or HLA epitope compatibility. Prospective studies are needed to further confirm the clinical benefit of new allo-antibodies identification methods and consensus strategies for immune platelet refractoriness management. [ABSTRACT FROM AUTHOR]