Extracorporeal Photopheresis versus Anticytokine Therapy as a Second-Line Treatment for Steroid-Refractory Acute GVHD: A Multicenter Comparative Analysis

Jagasia, Madan; Greinix, Hildegard; Robin, Marie; Das‐Gupta, Emma; Jacobs, Ryan; Savani, Bipin N.; Engelhardt, Brian G.; Kassim, Adetola A.; Worel, Nina; Knobler, Robert; Russell, Nigel H.; Socié, Gèrard

doi:10.1016/j.bbmt.2013.04.018

Cited by 85 publications

(56 citation statements)

References 17 publications

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“…A multicenter retrospective study in patients with SR acute GVHD showed a higher response rate to ECP than to anti-cytokine therapy, which translated into an overall survival benefit. 27 The cumulative 2-year NRM rate in patients who achieved 6-month FFTF was 22.4%, with infections accounting for 6.6% of the deaths. This suggests that ECP does not cause generalized immunosuppression leading to an increased risk of severe opportunistic infections.…”

Section: Discussionmentioning

confidence: 96%

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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Section: Discussionmentioning

confidence: 96%

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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“…121,122 Other immunosuppressants available include anti-IL-2 receptor-, anti-IL6 receptor-, anti-CD20-, and anti-CD52-targeted therapies. There is some data in support of extracorporeal photopheresis 123 and infusion of mesenchymal stromal cells (MSCs) 124 in refractory aGVHD. Current clinical trials available for the treatment of steroid-refractory aGVHD include a combination of basiliximab plus infliximab (combined targeting of the IL-2 receptor and TNFa, NCT01485055).…”

Section: Refractory and Steroid-resistant Agvhdmentioning

confidence: 99%

Acute graft-versus-host disease: a bench-to-bedside update

Holtan

Pasquini

Weisdorf

2014

Blood

172

131

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Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.

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“…20 ECP is successfully used to treat established acute and chronic GVHD especially in patients unresponsive to conventional immunosuppressive drugs and has been proven successful in prevention of solid organ rejection. [21][22][23] We hypothesized that administration of apoptotic cells prior to transplantation would induce unresponsiveness in the majority of immature DCs, consequently limit donor T-cell activation, and hence The online version of this article contains a data supplement.…”

Section: Introductionmentioning

confidence: 99%

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

Florek

Sega

Leveson-Gower

et al. 2014

Blood

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Key Points• Prophylactic ECP protects against GVHD in a murine BMT model.• ECP provides apoptotic signals that promote tolerance through dendritic cells and Tregs.Acute graft-versus-host disease (GVHD) is induced by alloreactivity of donor T cells toward host antigens presented on antigen-presenting cells (APCs). Apoptotic cells are capable of inducing tolerance by altering APC maturation. Apoptosis can be induced by extracorporeal photopheresis (ECP). We demonstrate that the use of ECP as a prophylaxis prior to conditioning significantly improves survival (P < .0001) after bone marrow transplantation (BMT) by inhibiting the initiation phase of acute GVHD in a murine BMT model. ECP-treated autologous splenocytes resulted in immune tolerance in the host, including reduced dendritic cell activation with decreased nuclear factor-kB engagement, increased regulatory T-cell (Treg) numbers with enhanced expression of cytolytic T lymphocyte-associated antigen 4, potentiating their suppressive function. The protective effect required host production of interleukin-10 and host Tregs. Conventional T cells that entered this tolerant environment experienced reduced proliferation, as well as a reduction of tissue homing and expression of activation markers. The induction of this tolerant state by ECP was obviated by cotreatment with lipopolysaccharide, suggesting that the inflammatory state of the recipient prior to treatment would play a role in potential clinical translation. The use of prophylactic ECP may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting. (Blood.

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Extracorporeal Photopheresis versus Anticytokine Therapy as a Second-Line Treatment for Steroid-Refractory Acute GVHD: A Multicenter Comparative Analysis

Cited by 85 publications

References 17 publications

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

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

Acute graft-versus-host disease: a bench-to-bedside update

Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

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