Post-Transplant High-Dose Cyclophosphamide for the Prevention of Graft-versus-Host Disease

Al-Homsi, Ahmad Samer; Roy, Tara S.; Cole, Kelli; Feng, Yi; Duffner, Ulrich

doi:10.1016/j.bbmt.2014.08.014

Cited by 111 publications

(83 citation statements)

References 43 publications

(50 reference statements)

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“…High doses of cyclophosphamide and sirolimus have been successfully used to prevent GVHD and have been shown to enhance the activity of Treg cells. [85][86][87] Although early studies have suggested a negative effect of cyclophosphamide on Treg cells, the role of Treg cells in the cyclophosphamide GVHD prophylactic effect, is essential. In the xenogenic GVHD mouse model, Kanakry and colleagues proved that when peripheral blood mononuclear cell grafts were depleted of Tregs, the humanized mice had severe GVHD scores and died earlier, and suggested the requirement of Treg cells for the optimal effect of cyclophosphamide.…”

Section: Mechanisms Underlying the Suppressive Function Of Foxp3 1 Trmentioning

confidence: 99%

FOXP3+ regulatory T cells and their functional regulation

et al. 2015

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Section: Mechanisms Underlying the Suppressive Function Of Foxp3 1 Trmentioning

confidence: 99%

FOXP3+ regulatory T cells and their functional regulation

et al. 2015

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“…Novel strategies of prevention GVHD may be more effective as compared to treatment of acute or chronic GVHD. Recent trials with the use of post-transplant cyclophosphamide in unrelated donor transplant have shown mixed results [167], but it was shown to be very effective in haploidentical donor HSCT. Inducible caspase 9 (iC9) suicide gene expressing T cells have been used to decrease incidence of GVHD and improve immune reconstitution and has shown promising results [168].…”

Section: Future Directionsmentioning

confidence: 99%

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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“…Whether early donor lymphocyte infusion after T-cell depleting strategies or high-dose cyclophosphamide post transplant counterbalance NRM versus relapse is the subject of much debate and investigation. 15,16 Chronic GvHD reduced the chance of relapse in many studies; however, in a recent registry study of the Center for International Blood and Marrow Transplant Research (CIBMTR), its impact seemed only clinically relevant for CML after myeloablative alloSCT and not for AML. 17 In this study, cGvHD was primarily associated with a higher transplant-related mortality (TRM).…”

Section: Transplant-related Factors In Relation To Relapse Risk Aftermentioning

confidence: 99%