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Monitoring the kinetics of B-cell recovery following rituximab may guide the management of steroid-refractory chronic GvHD

Bone Marrow Transplantation volume 51, pages 607–609 (2016)Cite this article

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Recent studies have demonstrated that activated donor B cells are central to the immunopathology of chronic GvHD (cGvHD).1 Following allogeneic hematopoietic stem cell transplantation, donor B-cell reconstitution occurs in the setting of factors, which promote the aberrant persistence of allo- and autoreactive B cells.2 Persistently elevated levels of B-cell activating factor (BAFF) during hematopoietic reconstitution lead to failure of physiological negative selection and promote the survival autoreactive B cells.3 These B cells clones produce auto- and alloantibodies that can lead to sclerosis and other clinical manifestations of cGvHD.4, 5 Traditional immunosuppressive therapies have targeted the T-cell compartment of the reconstituting immune system, but clinical responses to these agents have been limited, with failure-free survival after second line therapy being only 20%.6 The inability to achieve a robust B-cell tolerance is a hallmark of active cGvHD and approaches that incorporate B-cell-directed therapies have been studied to meet this clinical need.

Rituximab, a monoclonal anti-CD20 ab, has resulted in improvement of symptoms in patients with steroid-refractory cGvHD, especially those with sclerodermatous or lichenoid cutaneous manifestations, with response rates ranging from 43–83%.7, 8 However, our understanding of disease response to B-cell targeted treatment is still evolving. Given the typical extent of tissue sclerosis in cGvHD, it can be difficult to differentiate persistent active cGvHD from residual tissue damage without active inflammation based upon clinical criteria alone. This report describes how immunophenotypic evidence of normal B-cell recovery following B-cell depleting therapy with rituximab may be a clinical tool to evaluate disease response that may inform regarding clinical management.

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA

    Z DeFilipp, M Purcell, W A C Harris, C Gleason & E K Waller

  2. Medical College of Georgia, Georgia Reagents Univeristy, Augusta, GA, USA

    D J Chandra

  3. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA

    J Wrammert

  4. Division of Cell Therapy and Hematologic Malignancies, Department of Medicine, Duke Cancer Institute, Duke University, Durham, NC, USA

    S Sarantopoulos

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  1. Z DeFilipp
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  2. M Purcell
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  3. W A C Harris
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  7. S Sarantopoulos
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  8. E K Waller
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Correspondence to Z DeFilipp.

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DeFilipp, Z., Purcell, M., Harris, W. et al. Monitoring the kinetics of B-cell recovery following rituximab may guide the management of steroid-refractory chronic GvHD. Bone Marrow Transplant 51, 607–609 (2016). https://doi.org/10.1038/bmt.2015.304

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