Extracorporeal photopheresis in the management of graft-versus-host disease

Bredeson, Chris; Rumble, R. Bryan; Varela, Norma P.; Kuruvilla, John; Kouroukis, C. Tom

doi:10.3747/co.21.1882

Cited by 13 publications

(8 citation statements)

References 28 publications

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“…In a randomized trial, ECP was considered safe, and efficacy outcomes were in favor of ECP with substantial reduction in skin manifestations of chronic GvHD and a steroid‐sparing effect 3‐months following treatment . Among the challenges of using ECP therapy is the lag time between the onset of therapy and improvement of the clinical condition.…”

Section: Introductionmentioning

confidence: 99%

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Dunavin

Braun

et al. 2018

Adv Cell Gene Ther

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Chronic graft‐versus host disease (GvHD) affects approximately 30%‐70% of patients undergoing hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that is often used as a second‐line therapeutic option for steroid‐resistant chronic GvHD. There is a several week delay between the onset of ECP and clinical improvement in symptoms. Thus, a biomarker that precedes improvement in disease activity or predicts response to therapy would be of clinical value. In this study, we sought to determine how previously studied GvHD biomarkers change over a course of ECP therapy. Seven chronic GvHD biomarkers (ST2, MMP‐3, CXCL9, CXCL10, CXCL11, BAFF, and CD163) were measured by ELISA in 16 patients before and after 2 months of ECP. Initial ST2 levels were high compared to healthy donors and patient samples required more than the manufacturer‐recommended dilution. The median ST2 level decreased over the first 2 months of treatment (193 v. 96 ng/mL, P = 0.03); the other biomarkers did not change significantly. Serial ST2 levels at 2, 4, and 6 months after ECP initiation showed that ST2 levels declined over the course of therapy. The results of this study show that ST2 is substantially elevated and declines during therapy in patients who receive ECP as a second‐line therapy for chronic GvHD.

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Section: Introductionmentioning

confidence: 99%

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Dunavin

Braun

et al. 2018

Adv Cell Gene Ther

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“…Extracorporeal photopheresis (ECP) has been used to treat a number of immunologic diseases, although cutaneous T‐cell lymphoma is currently the only Food and Drug Administration–approved indication . An ECP treatment is composed of the ex vivo exposure of autologous white blood cells (WBCs) to a liquid formulation of 8‐methoxypsoralen (THERAKOS UVADEX, Therakos, Inc.) and ultraviolet A (UVA) light, followed by the subsequent reinfusion of the cells to the subject …”

mentioning

confidence: 99%

“…It is well established that a primary event leading to the clinical effect is exposure of a patient's WBCs to methoxsalen and UVA light. This treatment leads to induction of normal programmed cell death (i.e., apoptosis) in the treated buffy coat (BC) cells, which in turn initiates a number of secondary, disease‐dependent, responses when reinfused into the patient . A recent in vitro study has indicated that it might be possible to modulate the kinetics of apoptosis in WBC subpopulations by adjusting the duration of incubation with methoxsalen .…”

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confidence: 99%

“…Some investigators have posited that the apoptosis observed after ECP treatment might be primarily caused by the mechanical stresses, such as shear, turbulence, and centrifugal forces and pressures, rather than the treatment with methoxsalen . It is important to determine if these effects may have a significant contribution before launching clinical trials that include a sham control to address the biologic mechanisms of ECP.…”

mentioning

confidence: 99%

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Apheresis buffy coat collection without photoactivation has no effect on apoptosis, cell proliferation, and total viability of mononuclear cells collected using photopheresis systems

et al. 2018

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BACKGROUND Extracorporeal photopheresis (ECP) has been approved for the treatment of advanced cutaneous T‐cell lymphoma since 1988. While the precise mechanisms resulting in clinical effects are not fully understood, the photoactivation of mononuclear cells (MNCs) using ultraviolet A (UVA) light and methoxsalen is believed to be the predominant initiating process. The effects of MNC passage through the instrument without photoactivation are unknown. The objective of this study was to evaluate the effect of cell processing through the photopheresis instruments on MNCs. STUDY DESIGN AND METHODS Fourteen healthy male subjects underwent one simulated ECP procedure without reinfusion of buffy coats (BCs) in a two‐center, open‐label, prospective trial. Baseline peripheral blood BC, apheresis‐separated untreated BC (BC1), and photoactivated BC (BC2) were evaluated in culture for viability by dye exclusion, apoptosis by annexin V binding, and cell proliferation response to phytohemagglutinin (PHA) stimulation by bromodeoxyuridine (BrdU) incorporation. RESULTS Photoactivation (BC2) resulted in 88% expression of annexin V by Day 1 of culture compared with 37 and 39% for baseline and untreated BC1. Cell viability by propidium iodide exclusion was reduced to 10% in BC2 on Day 1 versus 65 and 60% for baseline and BC1. The proliferative response to PHA stimulation was 97% inhibited in the photoactivated BC2. CONCLUSIONS These results demonstrate that the mechanical processes used for cell separation and processing of the BC in the absence of photoactivation do not induce a significant amount of apoptosis compared to the standard ECP with methoxsalen and UVA photoactivation.

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“…Extracorporeal photopheresis (ECP), mycophenolate mofetil, sirolimus, everolimus, rituximab, and ibrutinib are available options. ECP is recommended in the treatment of steroid-resistant aGvHD [19] and was found to result in overall response rates of 50% to 65%. Table 2 provides a brief summary of some of the current novel second-line strategies for steroid-refractory aGvHD.…”

Section: Treatmentmentioning

confidence: 99%