Rituximab reduces the incidence of acute graft-versus-host disease

Christopeit, Maximilian; Schütte, V.; Theurich, Sebastian; Weber, Thomas; Grothe, Wilfried; Behre, Gerhard

doi:10.1182/blood-2009-01-200527

Cited by 36 publications

(26 citation statements)

References 10 publications

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“…4 Administration of rituximab before transplantation may have helped prevent EBV-PTLD, and recipient B-cell depletion may have contributed to the low GVHD incidence and severity. 30 In the past, ex vivo T-cell-depleted haplo-HSCTs have been performed either through positive selection of CD34 1 cells 31,32 or through removal of CD3…”

Section: Discussionmentioning

confidence: 99%

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion

Locatelli

Merli

Pagliara

et al. 2017

Blood

281

260

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Key Points• Children with AL given haplo-HSCT after ab T-and B-cell depletion are exposed to a low risk of acute and chronic GVHD and NRM.• The leukemia-free, GVHDfree survival of patients given this type of allograft is comparable to that of HLAmatched donor HSCT recipients.Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. We developed a novel method of graft manipulation based on negative depletion of ab T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. Eighty AL children, transplanted between September 2011 and September 2014, were enrolled in the trial. All children were given a fully myeloablative preparative regimen. Anti-T-lymphocyte globulin from day 25 to 23 was used for preventing graft rejection and graft-versus-host disease (GVHD); no patient received any posttransplantation GVHD prophylaxis. Two children experienced primary graft failure. The cumulative incidence of skin-only, grade 1-2 acute GVHD was 30%; no patient developed extensive chronic GVHD. Four patients died, the cumulative incidence of nonrelapse mortality being 5%, whereas 19 relapsed, resulting in a 24% cumulative incidence of relapse. With a median follow-up of 46 months for surviving patients, the 5-year probability of chronic GVHD-free, relapsefree survival (GRFS) is 71%. Total body irradiation-containing preparative regimen was the only variable favorably influencing relapse incidence and GRFS. The outcomes of these 80 patients are comparable to those of 41 and 51 children given transplantation from an HLA-identical sibling or a 10/10 allelic-matched unrelated donor in the same period. These data indicate that haplo-HSCT after ab T-and B-cell depletion represents a competitive alternative for children with AL in need of urgent allograft. This trial was registered at www.clinicaltrials.gov as #NCT01810120. (Blood. 2017;130(5):677-685)

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Section: Discussionmentioning

confidence: 99%

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion

Locatelli

Merli

Pagliara

et al. 2017

Blood

281

260

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“…The synergistic effects of mTor (mammalian target of rapamycin) and calcineurin inhibitors 17 or mTor inhibitors and mycophenolate mofetil 18 have been explored in prophylaxis regimens. Similarly, specific anti-T-and B-cell antibodies (such as alemtuzumab, 19 antithymocyte globulin, 20 rituximab 21,22 ) or antibodies against soluble GvHD effectors (such as infliximab and etanercept; see below) have been tested to prevent GvHD with some success, counterbalanced by a high incidence of severe opportunistic infections and disease relapse. Novel promising targeted treatments aim at interfering with the inflammatory cascade triggered by host alloantigen recognition by donor T cells.…”

Section: Prospectsmentioning

confidence: 99%

Progress and prospects: graft-versus-host disease

et al. 2010

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“…Recent studies showed an association between high numbers of donor B cells and the development of both acute and chronic GVHD (Shimabukuro-Vornhagen et al, 2009). And treatment with rituximab-a CD20-specifi c monoclonal antibody that depletes B cells before HSCT, reduced GVHD incidence (Christopeit et al, 2009). In addition, IVIG (intravenous immunoglobulin) was reported to prevent xenogeneic GVHD by inhibiting the reconstitution of B cells, but not T cells (Gregoire-Gauthier et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation

Tan

Xing

et al. 2013

Protein Cell

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Graft-versus-host disease (GVHD) is a prevalent and potential complication of hematopoietic stem cell trans-plantation. An animal model, xenogeneic GVHD (X-GVHD), that mimics accurately the clinical presentation of GVHD would provide a tool for investigating the mechanism involved in disease pathogenesis. Murine models indicated that inhibiting IL-21 signaling was a good therapy to reduce GVHD by impairing T cell functions. We sought to investigate the effect of exogenous human IL-21 on the process of X-GVHD. In this study, human IL-21 was expressed by hydrodynamic gene delivery in BALB/cRag2 −/− IL-2Rγc −/− (BRG) immunodeficient mice which were intravenously transplanted human peripheral blood mononuclear cells (hPBMCs). We found that human IL-21 exacerbated X-GVHD and resulted in rapid fatality. As early as 6 days after hPBMCs transplanted to BRG mice, a marked expansion of human CD19 + B cells, but not T cells, was observed in spleen of IL-21-treated mice. Compared with control group, IL-21 induced robust immunoglobulin secretion, which was accompanied by increased accumulation of CD19 + CD38 high plasma cells in spleen. In addition, we demonstrated that B-cell depletion was able to ameliorate X-GVHD. These results are the fi rst to fi nd in vivo expansion and differentiation of human B cells in response to IL-21, and reveal a correlation between the expansion of B cells and the exacerbation of xenogeneic GVHD. Our fi ndings show evidence of the involvement of B cells in X-GVHD and may have implications in the treatment of the disease.

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Rituximab reduces the incidence of acute graft-versus-host disease

Cited by 36 publications

References 10 publications

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion

Progress and prospects: graft-versus-host disease

IL-21 accelerates xenogeneic graft-versus-host disease correlated with increased B-cell proliferation

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