Monitoring the kinetics of B-cell recovery following rituximab may guide the management of steroid-refractory chronic GvHD.
Monitoring the kinetics of B-cell recovery following rituximab may guide the management of steroid-refractory chronic GvHD.
复制标题
监测利妥昔单抗后 B 细胞恢复的动力学可以指导类固醇难治性慢性 GvHD 的治疗。
DOI：
10.1038/bmt.2015.304
复制
发表时间：
2016
影响因子：
4.8
通讯作者：
Waller,EK
中科院分区：
文献类型：
--
作者：
DeFilipp,Z;Purcell,M;Harris,WAC;Chandra,DJ;Gleason,C;Wrammert,J;Sarantopoulos,S;Waller,EK
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. A 19-year-old female was diagnosed with extramedullary AML in the form of a right breast mass in August 2007. She received three cycles of induction chemotherapy and achieved a partial response. The patient subsequently underwent an allogeneic peripheral blood stem cell transplant in December 2007 from her HLA-matched sister (conditioning: busulfan (0.9 mg/kg× 16 doses), cyclophosphamide (60mg/kg× 2 doses); GvHD prophylaxis: cyclosporine, methotrexate). She developed acute upper gastrointestinal GvHD on day+ 30, which resolved with a brief course of steroids. AML relapsed 1 year after transplant with SC nodules on her scalp without hematologic relapse and progressed despite salvage therapy with pegylated interferon, decitabine and donor lymphocyte infusions. For refractory AML, the patient underwent a second allogeneic peripheral blood stem cell transplant in February 2009 from an HLA-matched unrelated donor (conditioning: fludarabine (25 mg/m2× 4 doses), melphalan (70 mg/m2× 2 doses); GvHD prophylaxis: tacrolimus, mycophenolate mofetil). Her second transplant was complicated by severe (Grade III) acute lower gastrointestinal GvHD on day+ 24, managed with high-dose steroids, tacrolimus, infliximab and
