Efficacy of Rituximab in the Setting of Steroid-Refractory Chronic Graft-versus-Host Disease: A Systematic Review and Meta-Analysis

Kharfan‐Dabaja, Mohamed A.; Mhaskar, Asmita; Djulbegoviĉ, Benjamin; Cutler, Corey; Mohty, Mohamad; Kumar, Amit

doi:10.1016/j.bbmt.2009.04.003

Cited by 116 publications

(87 citation statements)

References 25 publications

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“…Cutler et al [122] reported a response rate of 70 % with rituximab in treatment of steroid-refractory cGVHD. In another meta-analysis involving 111 patients a cumulative response rate of 66 % was observed with rituximab [123]. Responses with rituximab were mainly partial and were limited in skin and musculoskeletal disease.…”

Section: Rituximabmentioning

confidence: 98%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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Section: Rituximabmentioning

confidence: 98%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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“…Although several studies have suggested an effect on cGvHD in the skin, 66,[95][96][97][98] no convincing effect on BO has been established. 66,67 …”

Section: Rituximabmentioning

confidence: 99%

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

Uhlving

Buchvald

Heilmann

et al. 2011

Bone Marrow Transplant

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Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7-26% of the patients, with a reported mortality rate of 21-100%. It is considered a manifestation of chronic graftversus-host disease, but our knowledge of aetiology and pathogenesis is still limited. Diagnostic criteria are being developed, and will allow more uniform and comparable research activities between centres. At present, no randomised controlled trials have been completed that could demonstrate an effective treatment. Steroids in combination with other immunosuppressive drugs still constitute the backbone of the treatment strategy, and results from our and other centres suggest that monthly infusions of high-dose pulse i.v. methylprednisolone (HDPM) might stabilise the disease and hinder progression. This article provides an overview of the current evidence regarding treatment options for BO and presents the treatment results with HDPM in a paediatric national HSCT-cohort.

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“…In addition, B-cell related markers and antibodies have been recognized as biomarkers for characterization and scoring cGVHD (13,14). Finally, Rituximab, which depletes B cells, has been successfully used as cGVHD therapy (8,(15)(16)(17)(18)(19).…”

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confidence: 99%

H–Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease

Sahaf¹,

Yang

Arai³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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B cells are known to play an important role in pathogenesis of human chronic graft vs. host disease (cGVHD). Our group has previously shown that IgG allo-antibodies recognize Y chromosomeencoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 mo after transplant in male patients who receive grafts from female donors (F→M) hematopoietic cell transplantation (HCT). Here we present FACS studies of peripheral blood mononuclear cells collected 6 mo after transplant showing that 16 of 28 (57%) F→M HCT patients have circulating donor B cells that express B-cell receptor (mainly IgM and Igλ) specific for DBY-2. The detection of these DBY-2 B cells 6 mo after HCT are associated with cGVHD development (P = 0.004). Specifically, 15 of 16 F→M with DBY-2 B cells developed cGVHD. In contrast, cGVHD developed in only 5 of the 12 who did not have DBY-2 B cells detected. This demonstrates circulating human B cells binding an alloantigen (DBY-2) and that these DBY-2-specific B cells appear before development of cGVHD in roughly half of the F→M patients. Our study suggests that detection of anti-DBY-2 B cells may predict cGVHD and that this prediction may have clinical utility. Validation of this hypothesis will require larger prospective studies.allogeneic | antigen-specific B cells | transplantation | DDX3Y

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Efficacy of Rituximab in the Setting of Steroid-Refractory Chronic Graft-versus-Host Disease: A Systematic Review and Meta-Analysis

Cited by 116 publications

References 25 publications

State-of-the-art acute and chronic GVHD treatment

State-of-the-art acute and chronic GVHD treatment

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

H–Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease

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