Topic: 22. Stem cell transplantation - Clinical Background: Despite novel biologic agents, steroid-dependent or -refractory acute graft-versus-host disease (aGVHD) remains a severe complication of allogeneic hematopoietic cell transplantation (alloHCT). Aims: Based on our long-lasting experience with extracorporeal photopheresis (ECP), we aimed to prospectively assess the role of ECP as early second-line treatment in steroid-dependent and refractory aGVHD. Methods: We enrolled consecutive patients with steroid-dependent or refractory grade (gr) II-IV aGVHD post alloHCT over the last decade (January 2013 - December 2022). 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. Before ruxolitinib’s availability, ATG was commenced simultaneously with ECP initiation in steroid-refractory patients. Results: We studied 28 patients, aged 45 (18-67), post alloHCT with myeloablative (16), reduced toxicity (8) and intensity (4) conditioning, from sibling (4), matched (11) or one locus mismatched (12) volunteer unrelated and haploidentical (1) donors. Disease risk index was very high (1), high (11), intermediate (14) and low (2). Acute GVHD was observed at day +17 (8-50). Skin, intestine and liver involvement was evident in 9 patients, skin and intestine in 13 and skin only in 6 patients. Thirteen patients were steroid-dependent and 15 steroid-refractory. ECP was commenced at day +18 (8-56) for 15 (4-20) sessions. The majority of patients (19/27) presented partial (7), very good (11) or complete (1) response to ECP. With 9.9 (1.7-113) months of follow-up, immunosuppression was reduced in 12/27 and ceased in 1 patient. Clinically significant bacterial infections were found in 19 patients, fungal in 3, CMV and EBV reactivation in 19 and 12 respectively and other viral in 6 patients. Cumulative incidence (CI) of chronic GVHD was 56.4 at 1-year.Five-year overall survival (OS) was 34%. Reduction of immunosuppression (p=0.026) and number of ECP sessions (p<0.001) were associated with improved OS, irrespectively of other factors. In particular, optimal OS was observed in patients that received more than 19 ECP sessions (Figure). Summary/Conclusion: Our data confirm that ECP should be considered early in the course of steroid-dependent or refractory aGVHD, even in the era of novel biologic agents. Optimal timing of intervention, frequency, duration and tapering schedule of ECP remain important unanswered questions.Keywords: Allogeneic, Graft-versus-host disease (GVHD), Hematopoietic cell transplantation, Extracorporeal photopheresis
Relapsed or primary refractory Hodgkin's (HL) and Non Hodgkin's lymphomas (NHL) are rescued, with the potential of cure with autologous hematopoietic cell transplantation (AHCT). The conditioning regimens used are considered equal and none has demonstrated any superiority. During the last 2 years, primarily due to Carmustine (BCNU) unavailability, a new alternative conditioning regimen was constructed in our unit consisting of intravenous Busulphan (Busilvex) (3.2mg/kg/day for 3 days), Etoposide (400mg/m2/day for 2 days) and Melphalan (140mg/m2) (BEM). We retrospectively analysed the outcome of patients (pts) who underwent AHCT following conditioning with the standard BEAM and BEM regimen. The pts were stratified by age, pre-transplantation disease phase and previous lines of treatment. In total, 50 pts conditioned with BEM (group A) and 93 pts with BEAM (group B) were included. Group B pts were selected among 184 pts who underwent AHCT with BEAM regimen during the last decade. Stratification by disease risk was followed by a 1:2 selection. Fifty percent of the pts were younger than 34 in both study groups with a range of 11-68 years old. The pts of group B were more likely to suffer from HL (63) than NHL (30); whereas disease diagnosis for group A was HL in 28 and NHL in 22 pts. Disease was chemoresistant to salvage treatment in 46% of group A pts versus (vs) 23% of group B pts. There were no other significant differences concerning the patients' characteristics such as age above median, pre-transplantation lines of treatment (1-2: 40%, 3-4: 46%, ≥5: 14%), disease status (complete remission: 27%, primary refractory: 52%, relapse: 21%), advanced stage disease (52%). Complete remission post-AHCT was obtained in 50% of group A and 56% of group B pts. Progression free survival (PFS) at 2 years and overall survival (OS) were similar among the two study group populations (66% vs 63% and 80% vs 78% respectively). Given the fact that there were more pts with chemoresistant disease in group A, a second matched pair analysis was conducted upon stratification by disease chemosensitivity to salvage treatment instead of age as a risk factor. Efficacy was again similar for both conditioning regimens. In multivariate analysis favorable factors in terms of PFS were HL, chemosensitivity to salvage treatment and stage
