<scp>D</scp>iagnosis and management of acute graft‐versus‐host disease

Dignan, Fiona L.; Clark, Andrew; Amrolia, Persis; Cornish, Jacqueline; Jackson, Graham; Mahendra, Prem; Scarisbrick, Julia; Taylor, Peter; Hadžić, Nedim; Shaw, Bronwen E.; Potter, Michael; Transplantation, Marrow

doi:10.1111/j.1365-2141.2012.09129.x

Cited by 294 publications

(252 citation statements)

References 135 publications

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“…[5][6][7][8] However, GvHD diagnosis still almost completely relies on clinical symptoms, clinicians expertise and should be confirmed by histology studies. 27 Therefore, the identification of specific biomarkers detectable in PB samples could clearly become a valuable diagnostic and clinical tool to avoid invasive diagnostic procedures such as tissue biopsies. Moreover, it may help personalize treatment strategies in GvHD patients.…”

Section: Discussionmentioning

confidence: 99%

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation

Almici

Skert

Bruno

et al. 2017

Bone Marrow Transplant

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The physio-pathologic interrelationships between endothelium and GvHD have been better elucidated and have led to definition of the entity 'endothelial GvHD' as an essential early phase prior to the clinical presentation of acute GvHD. Using the CellSearch system, we analyzed circulating endothelial cells (CEC) in 90 allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients at the following time-points: T1 (pre-conditioning), T2 (pre-transplant), T3 (engraftment), T4 (onset of GvHD) and T5 (1 week after steroid treatment). Although CEC changes in allo-HSCT represent a dynamic phenomenon influenced by many variables (that is, conditioning, immunosuppressive treatments, engraftment syndrome and infections), we showed that CEC peaks were constantly seen at onset of acute GvHD and invariably returned to pre-transplant values after treatment response. Since we showed that CEC changes during allo-HSCT has rapid kinetics that may be easily missed if blood samples are drawn at pre-fixed time-points, we rather suggest an 'on demand' evaluation of CEC counts right at onset of GvHD clinical symptoms to possibly help differentiate GvHD from other non-endothelial complications. We confirm that CEC changes are a suitable biomarker to monitor endothelial damage in patients undergoing allo-transplantation and hold the potential to become a useful tool to support GvHD diagnosis (ClinicalTrials.gov NCT02064972).

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Section: Discussionmentioning

confidence: 99%

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation

Almici

Skert

Bruno

et al. 2017

Bone Marrow Transplant

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“…11 On the other hand, earlier animal models had suggested that TNF-a played a major role in aGVHD of gastrointestinal (GI) tract and skin. 19 The use of monoclonal antibodies against TNF-a is one of the possible therapeutic approaches for SR-aGVHD, but the efficacy is also limited when given independently and the incidence of CR was less than 40% in pilot studies. 12,20 However, signaling through the IL-2R plays a pivotal role, not only in the proliferation of effector T cells, but also in that of regulatory T cells (Tregs).…”

Section: Discussionmentioning

confidence: 99%

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Tan

Xiao

et al. 2017

OncoImmunology

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Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2-11) and of etanercept was 9 (range 2-12). At day 28 after starting the combination treatment, overall response (complete and partial response: CRCPR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p D 0.043, RR D 3.169), development of grades III-IV liver aGVHD (p D 0.007, RR D 5.034) and cytomegalovirus (CMV) reactivation (p D 0.035, RR D 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

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“…Multiple agents have been studied for SR acute GVHD. 4,[12][13][14] Augmenting immunosuppressive therapy may lead to clinical responses but has been associated with increased risk of relapse, due to a decrease in the graft-versustumor effect and non-relapse-related complications, especially serious opportunistic infections. The clinical response of acute GVHD in isolation can, therefore, be misleading for patients' overall outcome and is problematic when used as the main study endpoint for second-line therapy of acute GVHD.…”

Section: Introductionmentioning

confidence: 99%

Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure

et al. 2014

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Second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease remains ill-defined, due to limited efficacy of drugs and evolving clinical trial endpoints. Six-month freedom from treatment failure has been proposed as a novel clinical trial endpoint and is defined by the absence of death, malignancy relapse/progression, or addition of a next line of systemic immunosuppressive therapy within 6 months of intervention and prior to diagnosis of chronic graft-versus-host disease. We analyzed the 6-month freedom from treatment failure endpoint in 128 patients enrolled from three centers who were treated with extracorporeal photopheresis as second-line therapy for acute graft-versus-host disease. The incidence of 6-month freedom from treatment failure was 77.3% with a 2-year survival rate of 56%. Corticosteroid dose or response status at onset of second-line therapy did not influence outcome. Higher grade of acute graft-versus-host disease (grade 2 versus grades 3-4) at onset of photopheresis predicted for poor outcome as measured by survival (hazard ratio 2.78, P<0.001), non-relapse mortality (hazard ratio 2.78, P=0.001) and 6-month freedom from treatment failure (hazard ratio 3.05, P<0.001). For the 91 patients who achieved 6-month freedom from treatment failure, 1-year, 2-year and 3-year survival rates were 78.9%, 70.8% and 69.5%, respectively. Six-month freedom from treatment failure is a reasonable early surrogate for outcome and should be considered as a clinical trial endpoint. This study demonstrates the durable effect of photopheresis as second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease using 6-month freedom from treatment failure as the primary endpoint.

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Diagnosis and management of acute graft‐versus‐host disease

Cited by 294 publications

References 135 publications

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation

Circulating endothelial cell count: a reliable marker of endothelial damage in patients undergoing hematopoietic stem cell transplantation

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure

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