Retrospective Multicenter Study of Extracorporeal Photopheresis in Steroid-Refractory Acute and Chronic Graft-versus-Host Disease

Oarbeascoa, Gillen; Lozano, Marı́a Luisa; Guerra, Luisa Maria; Amunarriz, Cristina; Saavedra, Concepción Andón; García-Gala, José María; Viejo, Aurora; Revilla, Nuria; Fleitas, Cynthia Acosta; Arroyo, José Luis; Revuelta, Eva Martinez; Galego, Andrea; Hernández‐Maraver, Dolores; Kwon, Mi; Díez-Martin, José L.; Pascual, Cristina

doi:10.1016/j.bbmt.2019.12.769

Cited by 24 publications

(8 citation statements)

References 38 publications

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“…The clinical results appear in line with what is expected for both aGVHD and cGVHD. 1,20,21 ECP was effective in 87.5% and in 60% of patients affected by aGVHD and cGVHD respectively Furthermore, ECP also resulted in drug tapering in 87.5% and in 75% of patients affected by aGVHD and cGVHD respectively.…”

Section: Discussionmentioning

confidence: 98%

Inline and offline extracorporeal photopheresis: Device performance, cell yields and clinical response

Piccirillo

Putzulu

Massini

et al. 2020

J of Clinical Apheresis

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Background: Extracorporeal photopheresis (ECP) is an effective treatment for graft-vs-host-disease (GvHD). Photopheresis can be performed in offline or inline method. The first uses a conventional cell separator for collection of mononuclear-cells that are photoactivated by a separate device and manually reinfused; the second one involves a dedicated device performing the entire procedure (collection, photoactivation and reinfusion). Study design and methods: The objective was to compare the two methods and cell product features to highlight key process, devices performance, and to evaluate ECP clinical response. Patients developing steroid-resistant GvHD underwent ECP as second-line treatment using either inline (Therakos CellEx) or offline system (Terumo BCT Spectra or Optia and UVA PIT system). Data about patients' features, pre-apheresis blood-count, cell product characteristics and clinical response were collected for analysis. Results: We evaluated 494 procedures performed on 28 patients from April 2018 to March 2019. The offline procedure allows to achieve greater cell yield, it is characterized by larger processed blood volume, longer runtime, and higher ACD consumption. The inline procedure shows shorter runtime, high mononuclear-cells percentage and low percentage of granulocytes in cell product. We observed a significant difference in cell yields between inline and offline system; furthermore we did not find a significant relationship between cell dose and clinical response. Conclusion: Inline ECP is fast, highly automated and productive, making it particularly suitable for ECP treatments. Offline ECP collects high cell yields implying longer procedure and greater operator intervention. Our study did not find a significant relationship between cell dose and GVHD response.

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Section: Discussionmentioning

confidence: 98%

Inline and offline extracorporeal photopheresis: Device performance, cell yields and clinical response

Piccirillo

Putzulu

Massini

et al. 2020

J of Clinical Apheresis

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“…( 16 ) to have exerted satisfactory therapeutic effects on SR-cGVHD, supported by a favorable ORR of 85.4%. Among other commonly used second line cGVHD treatments, extracorporeal photopheresis (ECP) treatments were reported to achieve an ORR of 56.0% in a randomized controlled study ( 19 ) and an ORR of 67.0% in a retrospective multicenter study ( 20 ) of patients with cGVHD. In a large retrospective study including 269 patients with SR-cGVHD by Axt et al.…”

Section: Discussionmentioning

confidence: 99%

“…Ibrutinib, a Bruton tyrosine kinase inhibitor, showed a 67.0% ORR for patients with cGVHD in a multicenter, open-label study ( 22 ). Some researchers recruited only patients with moderate and severe cGVHD into study, while many studies included patients with mild to severe cGVHD ( 20 , 21 , 23 – 25 ). In our single-center retrospective survey conducted among 70 patients diagnosed with mild, moderate and severe cGVHD, the median follow-up time was 401 (range 6-1076) days.…”

Section: Discussionmentioning

confidence: 99%

Efficiency and Toxicity of Ruxolitinib as a Salvage Treatment for Steroid-Refractory Chronic Graft-Versus-Host Disease

et al. 2021

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Graft-versus-host disease (GVHD), especially steroid-refractory GVHD, remains a life-threatening complication after hematopoietic stem cell transplantation (HSCT). The effect of the JAK1/2 kinase inhibitor ruxolitinib on treating steroid-refractory acute GVHD has been verified by the REACH1/2 study; however, its safety and efficacy in patients with steroid-refractory chronic GVHD (SR-cGVHD) remain unclear. In this retrospective study, 70 patients received ruxolitinib as a salvage therapy for SR-cGVHD. Twenty-four weeks after ruxolitinib treatment, the overall response rate (ORR) was 74.3% (52/70), including 34 patients who achieved complete remission (CR) and 18 who achieved partial remission (PR). The main adverse event was cytopenia, which occurred in 51.4% (36/70) of patients. After ruxolitinib treatment, the percentage of CD4 cells increased from 18.20% to 23.22% (P<0.001), while the percentages of NK (CD16+CD56+) cells and regulatory T cells (CD4+CD127 ± CD25+) decreased (P<0.001, P<0.001). Among the B cell subsets, the proportion of total B cells approximately tripled from 3.69% to 11.16% (P<0.001). Moreover, we observed a significant increase in IL-10 levels after ruxolitinib treatment (P=0.025) and a remarkable decrease in levels of suppression of tumorigenicity 2 (ST2) from 229.90 ng/ml to 72.65 ng/ml. The median follow-up after the initiation of ruxolitinib treatment was 401 (6-1076) days. The estimated one-year overall survival rate of the whole group was 66.0% (54.4–77.6%, 95% CI), and the one-year overall survival rate of patients with mild and moderate cGVHD was 69.6% (57.4–81.8%, 95% CI), which was better than that of patients with severe cGVHD (31.3%, 0.0–66.2%, 95% CI) (P=0.002). Patients who achieved a CR and PR achieved better survival outcomes (84.5%, 73.9–95.1%, 95% CI) than those who showed NR to ruxolitinib treatments (16.7%, 0–34.3%, 95% CI) (P<0.001). At the final follow-up, cGVHD relapse occurred in six patients after they reduced or continued their ruxolitinib doses. Collectively, our results suggest that ruxolitinib is potentially a safe and effective treatment for SR-cGVHD.

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“…Among patients who achieved CR ( n = 7), one patient had a flare of aGVHD manifesting as recurrent gastrointestinal bleeding 11 . Patients with SR‐aGVHD can also be treated with extracorporeal photopheresis (ECP), but it was noted that there was still death due to RaGVHD 12 …”

Section: Introductionmentioning

confidence: 99%

“…11 Patients with SR-aGVHD can also be treated with extracorporeal photopheresis (ECP), but it was noted that there was still death due to RaGVHD. 12 Unmanipulated haploidentical allo-HCT with anti-thymocyte globulin (ATG) and G-CSF primed peripheral blood (PB) combined with bone marrow (BM) has been an established treatment for hematologic malignancies. The landscape of aGVHD either in the HCT with PB and BM or PB alone have been described.…”

mentioning

confidence: 99%

Increased risk of nonrelapse mortality post T‐cell‐replete haploidentical stem cell transplantation in patients with recurrence of acute graft‐versus‐host disease

Peng

Dou

Yang

et al. 2022

Hematological Oncology

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Acute graft-versus-host disease (aGVHD) causes significant morbidity and mortality. While most studies focus on classic or late aGVHD, some patients with previous aGVHD achieve complete remission and later develop another episode of aGVHD. Data on recurrence of aGVHD (RaGVHD) are lacking. This study aimed to identify the incidence, risk factors, and impacts of RaGVHD after T-cellreplete haploidentical hematopoietic cell transplantation (haplo-HCT) without posttransplantation cyclophosphamide. We evaluated patients with RaGVHD after haplo-HCT between 2017 and 2019 and compared their outcomes to those of patients with no aGVHD and those of patients with one episode of de novo aGVHD. Of 199 patients included in the analysis, 45 experienced 50 cases of RaGVHD with a 1-year cumulative incidence of 19.0% (95% CI: 14.5-24.6). Grade III-IV aGVHD was more common in RaGVHD than in previous aGVHD (22.2% vs. 4.4%, p = 0.01). Female donor to male recipient was strongly associated with RaGVHD (HR: 2.5, p = 0.009). The most common death in patients with RaGVHD was GVHD-related, which was different from controls who mostly died from relapse (p = 0.008). RaGVHD was an independent risk factor for chronic GVHD (HR: 2.6, p = 0.006) and nonrelapse mortality (HR: 2.4, p = 0.019) and a significant predictor of lower GVHD relapse-free survival (HR: 1.9, p = 0.020) and cGVHD relapse-free survival (HR: 2.1, p = 0.007). In conclusion, clinical manifestations and negative impacts of RaGVHD needs to be recognized independently.

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Retrospective Multicenter Study of Extracorporeal Photopheresis in Steroid-Refractory Acute and Chronic Graft-versus-Host Disease

Cited by 24 publications

References 38 publications

Inline and offline extracorporeal photopheresis: Device performance, cell yields and clinical response

Inline and offline extracorporeal photopheresis: Device performance, cell yields and clinical response

Efficiency and Toxicity of Ruxolitinib as a Salvage Treatment for Steroid-Refractory Chronic Graft-Versus-Host Disease

Increased risk of nonrelapse mortality post T‐cell‐replete haploidentical stem cell transplantation in patients with recurrence of acute graft‐versus‐host disease

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