EXTRACORPOREAL PHOTOPHERESIS IN STEROID-DEPENDENT OR REFRACTORY ACUTE GRAFT-VERSUS-HOST DISEASE
(Abstract release date: 05/18/17)
EHA Library. Gavriilaki E. 05/18/17; 182879; PB2166
Dr. Eleni Gavriilaki
Contributions
Contributions
Abstract
Abstract: PB2166
Type: Publication Only
Background
Extracorporeal photopheresis (ECP) has been incorporated in the management of graft-versus-host disease (GVHD) post allogeneic haematopoietic cell transplantation (alloHCT) in many centres. The introduction of ECP as an early second-line treatment in steroid-dependent or refractory patients with acute GVHD (aGVHD) remains under study. The rationale of its early use is based on the low incidence of complete responses to corticosteroids and the profound immunosuppression caused by traditional secondary treatments.
Aims
Based on our long-lasting experience in chronic GVHD, we aimed to prospectively assess the role of ECP in this high-risk population.
Methods
We enrolled consecutive patients with steroid-dependent or refractory grade (gr) II-IV aGVHD post alloHCT from January 2013 to August 2016. All patients with unrelated or haploidentical donors received thymoglobulin (ATG) 5mg/kg as prophylaxis. Post-transplant GVHD prophylaxis included cyclosporine – methotrexate in myeloablative and cyclosporine – mycophenolate mofetil in reduced toxicity or intensity regimens. ECP was commenced after assessment of response to 5 days of steroid treatment according to our protocol: 2 sessions/week for 1 month, 1 session/2 weeks for 3 months, evaluation of response and 1 session/month for 6 months.
Results
We studied 20 patients, aged 35 (18-65), post alloHCT with myeloablative (14), reduced toxicity (4) and intensity (4) conditioning, from sibling (3), matched (8) or one locus mismatched (8) volunteer unrelated and haploidentical (1) donors. Disease risk index was high (10), intermediate (9) and low (1). Acute GVHD was observed at day +17 (8-50) in 15 patients, late-onset at + 130 (110-160) in 4 patients and induced at +38 post donor lymphocyte infusion in a relapsed AML patient. Skin, intestine and liver involvement was evident in 6 patients, skin and intestine in 10 and skin only in 4 patients. Nine patients (2 with GrII, 7 with GrIII aGVHD) were steroid-dependent and 11 (8 with GrIII, 3 with GrIV) steroid-refractory. ATG was administered simultaneously with ECP initiation in 6 refractory patients that further developed EBV reactivation (p=0.032) treated pre-emptively with rituximab.
ECP was commenced at day +51 for 16 (4-20) sessions. The majority of patients (16/20) presented partial (6), very good (9) or complete (1) response to ECP. With 9.3 (1.8-54.7) months of follow-up, immunosuppression was reduced in 10/20 and ceased in 1 patient. Clinically significant bacterial infections were found in 17 patients, fungal in 2, CMV and EBV reactivation in 14 and 13 respectively and other viral in 5 patients.
Cumulative incidence (CI) of chronic GVHD was 77.4 at 1-year. 1-year CI of aGVHD-related mortality was 20%. 1-year overall survival (OS) was 53% and significantly increased in steroid-dependent versus refractory patients (76% vs 36%, p=0.041). Reduction of immunosuppression (p=0.026) and steroid dependence (p=0.023) were associated with improved OS, irrespectively of other factors.
Conclusion
Our study supports that ECP should be considered early in the course of steroid-dependent or refractory aGVHD, before significant irreversible end organ damage has been established. Optimal timing of intervention, frequency, duration and tapering schedule of ECP need to be investigated in future studies.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Graft-versus-host disease (GVHD), Extracorporeal photopheresis
Abstract: PB2166
Type: Publication Only
Background
Extracorporeal photopheresis (ECP) has been incorporated in the management of graft-versus-host disease (GVHD) post allogeneic haematopoietic cell transplantation (alloHCT) in many centres. The introduction of ECP as an early second-line treatment in steroid-dependent or refractory patients with acute GVHD (aGVHD) remains under study. The rationale of its early use is based on the low incidence of complete responses to corticosteroids and the profound immunosuppression caused by traditional secondary treatments.
Aims
Based on our long-lasting experience in chronic GVHD, we aimed to prospectively assess the role of ECP in this high-risk population.
Methods
We enrolled consecutive patients with steroid-dependent or refractory grade (gr) II-IV aGVHD post alloHCT from January 2013 to August 2016. All patients with unrelated or haploidentical donors received thymoglobulin (ATG) 5mg/kg as prophylaxis. Post-transplant GVHD prophylaxis included cyclosporine – methotrexate in myeloablative and cyclosporine – mycophenolate mofetil in reduced toxicity or intensity regimens. ECP was commenced after assessment of response to 5 days of steroid treatment according to our protocol: 2 sessions/week for 1 month, 1 session/2 weeks for 3 months, evaluation of response and 1 session/month for 6 months.
Results
We studied 20 patients, aged 35 (18-65), post alloHCT with myeloablative (14), reduced toxicity (4) and intensity (4) conditioning, from sibling (3), matched (8) or one locus mismatched (8) volunteer unrelated and haploidentical (1) donors. Disease risk index was high (10), intermediate (9) and low (1). Acute GVHD was observed at day +17 (8-50) in 15 patients, late-onset at + 130 (110-160) in 4 patients and induced at +38 post donor lymphocyte infusion in a relapsed AML patient. Skin, intestine and liver involvement was evident in 6 patients, skin and intestine in 10 and skin only in 4 patients. Nine patients (2 with GrII, 7 with GrIII aGVHD) were steroid-dependent and 11 (8 with GrIII, 3 with GrIV) steroid-refractory. ATG was administered simultaneously with ECP initiation in 6 refractory patients that further developed EBV reactivation (p=0.032) treated pre-emptively with rituximab.
ECP was commenced at day +51 for 16 (4-20) sessions. The majority of patients (16/20) presented partial (6), very good (9) or complete (1) response to ECP. With 9.3 (1.8-54.7) months of follow-up, immunosuppression was reduced in 10/20 and ceased in 1 patient. Clinically significant bacterial infections were found in 17 patients, fungal in 2, CMV and EBV reactivation in 14 and 13 respectively and other viral in 5 patients.
Cumulative incidence (CI) of chronic GVHD was 77.4 at 1-year. 1-year CI of aGVHD-related mortality was 20%. 1-year overall survival (OS) was 53% and significantly increased in steroid-dependent versus refractory patients (76% vs 36%, p=0.041). Reduction of immunosuppression (p=0.026) and steroid dependence (p=0.023) were associated with improved OS, irrespectively of other factors.
Conclusion
Our study supports that ECP should be considered early in the course of steroid-dependent or refractory aGVHD, before significant irreversible end organ damage has been established. Optimal timing of intervention, frequency, duration and tapering schedule of ECP need to be investigated in future studies.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Graft-versus-host disease (GVHD), Extracorporeal photopheresis
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