Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab

Benson, Don M.; Smith, Michael K.; Krugh, Dave; Devine, Steven M.

doi:10.1038/sj.bmt.1705945

Cited by 8 publications

(9 citation statements)

References 10 publications

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“…Several rare manifestations of chronic GVHD such as immune-mediated thrombocytopenia and pure red cell aplasia have also been reported to respond to rituximab treatment. 94,104 Addition of rituximab to prednisone may enable successful steroid tapering. B-cell depletion may therefore be a promising approach for the treatment of chronic GVHD, particularly steroid-refractory skin disease.…”

Section: B Cells and Chronic Gvhdmentioning

confidence: 99%

The role of B cells in the pathogenesis of graft-versus-host disease

Shimabukuro‐Vornhagen

Hallek

Storb

et al. 2009

Blood

239

194

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IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is an established, potentially curative treatment modality for malignant and nonmalignant hematologic diseases. Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic HSCT and limits its wider use. Traditionally, GVHD has been divided into 2 forms, acute and chronic, based on the time of its onset. Acute GVHD has been defined as disease occurring in the first 100 days after transplantation, whereas chronic GVHD occurs after day 100. This arbitrary distinction based on the time of onset fails to reflect the different pathophysiologic mechanisms and clinical manifestations of acute and chronic GVHD, however. Acute GVHD can occur after day 100 in patients who received a nonmyeloablative conditioning regimen or donor lymphocyte infusions. In addition, GVHD with typical clinical features of chronic GVHD can develop well before day 100 and concurrent with acute GVHD. Therefore, the National Institutes of Health consensus development project has defined new criteria for the diagnosis, staging, and response assessment of chronic GVHD. 1,2 Only a few effective therapies are currently available for the treatment of both forms of GVHD. The established immunosuppressive agents are mostly nonspecific and unfortunately associated with severe side effects, in particular the susceptibility to lifethreatening infections. Therefore, novel more selective agents are urgently needed.GVHD is an immune-mediated disease that results from a complex interaction between donor and recipient adaptive immunity. Donor-derived CD4 ϩ and CD8 ϩ T lymphocytes have classically been considered to be the main effector cells mediating GVHD pathogenesis. In fact, removal of T cells from transplant inocula almost completely prevents GVHD from developing, however, at the price of increased incidences of graft rejection and disease recurrence. In recent years, basic and clinical research has provided a more detailed mechanistic understanding of the molecules and cell types involved in the biology of the graft-versushost reaction.Because acute GVHD is thought to be mediated mainly by donor T cells, preventive and therapeutic treatment strategies have focused primarily on the inhibition of T-cell function. Recent animal studies suggest that B cells might also play an important role in the biology of GVHD. Further circumstantial evidence for the involvement of B cells in GVHD pathogenesis comes from reports of successful treatment of GVHD with B-cell depletion. The mechanisms by which B cells contribute to acute and chronic GVHD currently are only incompletely understood. Here, we provide an overview of the experimental and clinical evidence for a pathogenic role of B cells in GVHD and evaluate the implications with regard to B cell-targeted therapies for the treatment of GVHD. We conclude by providing an outlook on novel B cell-specific approaches that might prove beneficial for the treatment of GVHD. B-cell functions in health and diseaseB cells ar...

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Section: B Cells and Chronic Gvhdmentioning

confidence: 99%

The role of B cells in the pathogenesis of graft-versus-host disease

Shimabukuro‐Vornhagen

Hallek

Storb

et al. 2009

Blood

239

194

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“…CRRs were universally low. Organ responses were variable amongst the different studies; however, better responses were achieved in those patients with skin, musculoskeletal, and hematological manifestations [117–128]. Ocular manifestations were consistently poorly responsive to rituximab therapy [121, 122, 124, 127].…”

Section: Experience With Rituximab In Immune‐mediated Hematological Dmentioning

confidence: 99%

Anti‐CD20 monoclonal antibodies and their use in adult autoimmune hematological disorders

et al. 2011

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Autoimmune hematological disorders encompass a broad group of hematological conditions characterized by the loss of self-tolerance to a variety of antigens. Despite good response to first-line therapy in the majority of patients, relapses are common, necessitating new and safe therapeutic options. The anti-CD20 monoclonal antibody rituximab has led to substantial improvement in the treatment of malignant and immune-mediated disorders involving B cells. Although experience with rituximab in immune-mediated hematological disorders is rarely supported by randomized trials, there is now substantial experience with rituximab suggesting that anti-CD20 therapy is an effective and well-tolerated alternative to immunosuppressive therapy in these disorders. However, caution is needed based on recent reports describing-sometimes severe-rituximab-related complications.

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“…For this purpose, a number of studies have analyzed the potential of rituximab in patients with cGVHD and have observed several positive effects, mostly including skin manifestations of cGVHD. 69,71,72,[86][87][88][89][90] A summary of all these studies is presented in Table 3. However, among many of the responding cGVHD patients, rituximab failed to establish a complete recovery.…”

Section: Treatment Of Cgvhd With Rituximabmentioning

confidence: 99%

“…Addition of daclizumab was necessary to achieve complete clinical response as well as complete decrease of BP titer. Benson Jr et al 90 Improvement of pure red cell aplasia as a manifestation of cGVHD, 1 out of 1 as evident from increased reticulocytes and persistent normalization of hemoglobin levels.…”

mentioning

confidence: 99%

“…50 Also, the fact that several positive effects of treatment with rituximab in cGVHD patients have been found, further strengthens the involvement of B cells in cGVHD. 69,71,72,[86][87][88][89][90] Alternatively, a potential role of B cells as antigen-presenting cells in cGVHD can be considered. Antibodies in the plasma membrane (B-cell antigen receptors) may facilitate the uptake of extracellular antigens via receptor-mediated endocytosis.…”

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confidence: 99%

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B-cell involvement in chronic graft-versus-host disease

Kapur¹,

Ebeling²,

Hagenbeek³

2008

Haematologica

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Chronic graft-versus-host disease is a serious complication in long-term survivors of allogeneic hematopoietic stem cell transplantation, with several organ systems affected. Chronic graft-versus-host disease is an important cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation. This article reviews the pathogenesis of chronic graft-versus-host disease. In particularly, the role of B cells in chronic graft-versus-host disease is evaluated, as is evident from several studies which have investigated the presence of antibodies as well as studies which have analyzed B cells as a target for immunotherapy. Thirty autoantibodies and 5 alloantibodies have been identified in chronic graft-versus-host disease patients in 24 studies, and 8 autoantibodies and 5 alloantibodies seemed to be strongly associated with chronic graft-versus-host disease. In addition, various studies have observed significant improvements in chronic graft-versus-host disease using the anti-CD20 + antibody rituximab. However, it appears to be highly likely that both B cells as well as T cells are of major importance in chronic graft-versus-host disease. Further research is required to clarify the pathogenesis of chronic graft-versus-host disease.

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Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab

Cited by 8 publications

References 10 publications

The role of B cells in the pathogenesis of graft-versus-host disease

The role of B cells in the pathogenesis of graft-versus-host disease

Anti‐CD20 monoclonal antibodies and their use in adult autoimmune hematological disorders

B-cell involvement in chronic graft-versus-host disease

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