Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation

Pecoraro, Ylenia; Carillo, Carolina; Diso, Daniele; Mantovani, Sara; Cimino, Giuseppe; Giacomo, Tiziano De; Troiani, P.; Shafii, M.; Gherzi, Lorenzo; Amore, Davide; Rendina, Erino Angelo; Venuta, Federico; Anile, Marco

doi:10.1016/j.transproceed.2017.02.035

Cited by 20 publications

(16 citation statements)

References 19 publications

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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 …”

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confidence: 99%

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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confidence: 99%

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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“…Slowing of the rate of FEV1PP decline has been reported in HCT-related BOS after ECP therapy [7,8] and also in patients treated without ECP [21]; however, only 1 study has compared PFT results between ECP-and non-ECP-treated patients. In that particular post-lung transplantation study, Pecoraro et al [9] reported that FEV1PP values at 12 months after BOS diagnosis were higher for ECPtreated patients (n = 15) than for non-ECP-treated patients (n = 39). The former group, however, had higher FEV1PP values at BOS diagnosis, which, in the absence of matched paired data analysis, may have confounded the results.…”

Section: Discussionmentioning

confidence: 94%

“…Thus, because of suboptimal responses to medical therapies, extracorporeal photopheresis (ECP) has been used as an immunomodulatory alternative treatment for BOS. A few small cohort studies on BOS after lung transplantation have indicated that ECP may stabilize pulmonary function test (PFT) results and improve survival [7][8][9]. However, to the best of our knowledge, there are only 3 published single-center retrospective studies on the utility of ECP for BOS after HCT [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Extracorporeal Photopheresis Improves Survival in Hematopoietic Cell Transplant Patients with Bronchiolitis Obliterans Syndrome without Significantly Impacting Measured Pulmonary Functions

Hefazi

Langer

Khera

et al. 2018

Biology of Blood and Marrow Transplantation

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We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non-ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV percentage predicted (FEV) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non-ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, -9.5 versus -1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.

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“…There are recent investigations, including a clinical trial, examining the use of ECP in lung transplant rejection . One center showed that 80% of patients (n = 12 out of 15) treated with ECP experienced stabilization in their pulmonary function (−6% to 8% of forced expiratory volume in 1 second [FEV1] range from baseline) with a mean follow‐up of 11.6 months and no adverse events reported .…”

Section: Resultsmentioning

confidence: 99%

“…There are recent investigations, including a clinical trial, examining the use of ECP in lung transplant rejection. 21,22 One center showed that 80% of patients (n = 12 out of 15) treated with ECP experienced stabilization in their pulmonary function (−6% to 8% of forced expiratory volume in 1 second [FEV1] range from baseline) with a mean follow-up of 11.6 months and no adverse events reported. 23 For the treatment of rejection, one ECP procedure performed on back-to-back days for a total of two procedures, or one cycle, is often used, and cycles can range anywhere from 6 to 24.…”

Section: Lung Transplantationmentioning

confidence: 99%

The apheresis management of patients undergoing transplantation: a concise review

et al. 2019

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Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation

Cited by 20 publications

References 19 publications

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

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

Extracorporeal Photopheresis Improves Survival in Hematopoietic Cell Transplant Patients with Bronchiolitis Obliterans Syndrome without Significantly Impacting Measured Pulmonary Functions

The apheresis management of patients undergoing transplantation: a concise review

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