Extracorporeal photopheresis in 62 patients with acute and chronic GVHD: Results of treatment with the COBE Spectra System

Hautmann, A. H.; Wolff, Daniel; Hahn, J.; Edinger, Matthias; Schirmer, N.; Ammer, Julia; Holler, Barbara; Landfried, Karin; Hautmann, Matthias G.; Ahrens, Norbert; Ugocsai, Peter; Andreesen, Reinhard; Holler, Ernst

doi:10.1038/bmt.2012.156

Cited by 46 publications

(39 citation statements)

References 33 publications

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“…The reported ORR to MMF range between 15% and 31% 29, 30 . The reported ORR of aGVHD to ECP range between 47% and 65% 31–34 . Antibodies against TNF (etanercept, infliximab) are used as second-line agents for SR-aGVHD with a wide range of ORR reported 35 .…”

Section: Discussionmentioning

confidence: 99%

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey

Zeiser¹,

Burchert²,

Lengerke³

et al. 2015

Leukemia

473

386

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Despite major improvements in allogeneic hematopoietic cell transplantation over the last decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Pre-clinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage-therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grade III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1–7) and SR-cGVHD (1–10). The ORR was 81.5% (44/54) in SR-aGVHD including 25 CRs (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3%–90.7%,95% CI) and 97.4% (92.3%–100%,95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and CMV-reactivation were observed during ruxolitinib-treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

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Section: Discussionmentioning

confidence: 99%

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey

Zeiser¹,

Burchert²,

Lengerke³

et al. 2015

Leukemia

473

386

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“…ECP was performed as described previously in detail. 2,27 In brief, the Cellex system (Therakos, USA) was used with a protocol of two treatments per week for the first 4 weeks and two treatments every other week for the following 12 weeks. A blood volume of 750-1500 mL was processed according to the body weight of the patients and white blood cells were separated from RBCs.…”

Section: Patients and Ecp Treatmentmentioning

confidence: 99%

“…[24][25][26] aGvHD was graded by staging the affected organs, particularly skin, liver and gut (stage 1-4) and subsequently determining an overall grade (grade I-IV). 2 Grading of cGvHD was performed by scoring the organ involvement (score 0-3) and global severity grading (mild, moderate, severe). Mild cGvHD implicating no clinically relevant functional impairment was characterized by involvement of p2 organs (except of the lung) with a maximum score of 1 in all affected organs.…”

Section: Patients and Ecp Treatmentmentioning

confidence: 99%

“…Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory approach, 1 combining psoralen and UVA radiation, and has been shown to be efficient in a variety of T-cellmediated diseases, including severe steroid-resistant, acute 2 or chronic GvHD (aGvHD or cGvHD). 3,4 Despite its clinical effectiveness, the immunomodulatory mechanisms of ECP are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor cells in patients with GvHD

Rieber

Wecker

Neri

et al. 2014

Bone Marrow Transplant

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Extracorporeal photopheresis (ECP) is beneficial in patients with T-cell-mediated disorders, including GvHD, but the underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their capacity to suppress T-cell proliferation. We quantified MDSCs by flow cytometry in peripheral blood from patients after BMT with GvHD before and after ECP treatment, patients after BMT but without GvHD and age-matched healthy controls. MDSC functionality was analyzed using T-cell proliferation, cytokine release and arginase activity. GvHD patients showed increased baseline percentages of neutrophilic MDSCs (PMN-MDSCs) compared with healthy controls and patients after BMT without GvHD. ECP treatment in GvHD patients rapidly increased circulating percentages of PMN-MDSCs. Functionally, PMN-MDSCs efficiently dampened Th1 and Th17 responses and were paralleled by an increase of cellular and extracellular arginase activity. Following ECP longitudinally over 16 weeks, two GvHD responder subgroups were identified, with group one continuously increasing PMN-MDSCs and group two with stable or decreasing PMN-MDSCs over time. This study demonstrates for the first time that ECP increases T-cell-dampening PMN-MDSCs in GvHD patients, a finding that should be confirmed in larger series of GvHD patients.

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“…After three months of ECP treatment, there was a significant reduction of the hormone dose in 83% of patients with aGVHD and in 29% of patients with cGVHD. Overall survival significantly improved after allo-stem cell transplantation (28).…”

Section: Introductionmentioning

confidence: 99%

Previously Activated Psoralen: A Possible Novel Format of Psoralen used in the Treatment of Graft-versus-Host Disease

Hu¹,

Qian²,

Chen³

et al. 2015

West Indian Med J

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Extracorporeal photopheresis in 62 patients with acute and chronic GVHD: Results of treatment with the COBE Spectra System

Cited by 46 publications

References 33 publications

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey

Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor cells in patients with GvHD

Previously Activated Psoralen: A Possible Novel Format of Psoralen used in the Treatment of Graft-versus-Host Disease

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