Rituximab for second desensitization in patients with rebound of donor-specific anti-HLA antibodies before T-replete haplo-transplant using high-dose post-transplant cyclophosphamide

Garnier, Alice; Delbos, Florent; Guillaume, Thierry; Péterlin, Pierre; Bourgeois, Amandine Le; Béné, Marie C.; Bris, Yannick Le; Malard, Stéphanie; Duquesne, Alix; Gauvrit, Isabelle; Moreau, Philippe; Cesbron, Anne; Chevallier, Patrice

doi:10.1038/s41409-018-0107-7

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…Rituximab has been demonstrated to be effective in dealing with DSA‐mediated organ transplant rejection 27,28 . Several previous studies also reported that rituximab could be used for DSA desensitization in patients receiving Haplo‐HSCT 21,29–32 . Recently, Chang et al 33 demonstrated that treating DSA‐positive patients with a single dose of rituximab significantly decreased levels of DSA MFI and reduced primary PGF in patients with DSA 2000 ≤ MFI < 5000.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 Several previous studies also reported that rituximab could be used for DSA desensitization in patients receiving Haplo-HSCT. 21,[29][30][31][32] Recently, Chang et al 33 demonstrated that treating DSA-positive patients with a single dose of rituximab significantly decreased levels of DSA MFI and reduced primary PGF in patients with DSA 2000 ≤ MFI < 5000. In our protocol, a single dose of rituximab (375 mg/m 2 ) was administrated after completion of DFPP.…”

Section: Discussionmentioning

confidence: 99%

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Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Liu,

Ji,

Zhu

et al. 2023

Br J Haematol

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SummaryDonor‐specific anti‐HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo‐HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case–control study. Thirty‐three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10–21) and 13 (10–29) days respectively. Although the cumulative incidence of II–IV aGVHD (41.4% vs. 28.1%) and 3‐year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3‐year non‐relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo‐HSCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Liu,

Ji,

Zhu

et al. 2023

Br J Haematol

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“…In a pre-transplant setting, current treatment strategies for sensitized patients have partial or transient efficacy and include the use of plasma exchange, anti-CD20 monoclonal antibody therapy with rituximab, or blocking macrophage FcγR with high-dose intravenous immunoglobulin 43 . Fostamatinib treatment presents a potential alternative strategy in preventing allosensitization in both pre-transplant and post-transplant blood transfusions.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization

Tempest-Roe

Prendecki

McAdoo

et al. 2022

Sci Rep

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Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.

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“…In some studies, rituximab has been claimed to be an effective treatment modality for HLA-mediated rejections of renal transplants 23,24. In recent years, the use of rituximab for desensitization in AHSCT has also been tried, but there is no standard protocol yet 25,26. In a prospective clinical cohort study enrolled by Chang et al,27 rituximab was administered at a single dose of 375 mg/m 2 to 55 sensitized patients before HLA-mismatched transplantation and speculated that it decreases antibody titers and primary graft failure risk significantly so that it is an effective method for desensitization.…”

Section: Discussionmentioning

confidence: 99%

“…23,24 In recent years, the use of rituximab for desensitization in AHSCT has also been tried, but there is no standard protocol yet. 25,26 In a prospective clinical cohort study enrolled by Chang et al, 27 rituximab was administered at a single dose of 375 mg/m 2 to 55 sensitized patients before HLA-mismatched transplantation and speculated that it decreases antibody titers and primary graft failure risk significantly so that it is an effective method for desensitization. We also applied rituximab to 11 patients, 8 of which were combined with steroid and/or PP and engraftment was successful in 10 of eleven cases.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Panel Reactive Antibodies and Different Desensitization Methods on Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Outcomes

Akıncı

Akçay

Yenigürbüz

et al. 2021

Journal of Pediatric Hematology/Oncology

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Introduction:In highly sensitized patients who have panel reactive antibodies (PRAs) before hematopoietic stem cell transplantation, primary graft failure risk may increase. In this study, we aimed to determine the association of PRA with engraftment, and graft versus host disease (GVHD) in pediatric patients.Materials and Methods: Forty-three PRA-positive and 42 PRAnegative patients were taken into study. Both groups were compared in terms of graft failure, acute GVHD, viral infection and survival rates. PRA-positive group was also divided into 2 according to treatment modality (steroid-only group/combination therapy) and compared for the same parameters.Results: There was no difference in PRA-positive and negative patients in terms of graft failure, acute GVHD and viral infections. Analysis of the PRA-positive group in itself showed that there was also no difference in terms of graft failure and viral infection frequency. The only difference is that acute grade 3 to 4 GVHD was higher in the steroid-only group. The 100-day overall survival was 90.2% and 90.4% for the PRA-positive and negative groups, respectively.Conclusions: Different treatment strategies like plasmapheresis, steroid, rituximab, or combination therapies can be used for the desensitization of PRA-positive patients before hematopoietic stem cell transplantation. Patient-specific treatment modality for sensitized patients before transplant can increase the success rate.

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Rituximab for second desensitization in patients with rebound of donor-specific anti-HLA antibodies before T-replete haplo-transplant using high-dose post-transplant cyclophosphamide

Cited by 4 publications

References 8 publications

Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Double filtration plasmapheresis combined with rituximab for donor‐specific antibody desensitization in haploidentical haematopoietic stem cell transplantation

Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization

The Impact of Panel Reactive Antibodies and Different Desensitization Methods on Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Outcomes

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