scholarly journals 1088. Extracorporeal Photopheresis and Infectious Complications in Patients with Chronic Graft Versus Host Disease

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S573-S573
Author(s):  
Nida Ashraf ◽  
Ajoy Dias ◽  
Lisa A Clough ◽  
Yonghui Ni ◽  
Prabhakar Chalise ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Infectious Complications ◽  
Rank Test ◽  
Second Line ◽  
Extracorporeal Photopheresis ◽  
Host Disease ◽  
Graft Versus Host ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Increased Risk

Abstract Background Extracorporeal photopheresis (ECP), is a cell-based immune-modulatory therapy used in the treatment of steroid refractory chronic graft versus host disease (cGHVD). It is unclear whether ECP is associated with an increased risk of infections compared to alternative treatment. We aimed to study the infectious complications in patients who are on ECP post allogeneic hematopoietic stem cell transplant (alloHSCT). Methods We conducted a retrospective cohort study of adult patients with cGVHD post alloHSCT who were initiated on ECP or second line immunosuppressive agents (SLIS). The study period was from March 1, 2014 to October 1, 2018. Each subject in the ECP arm was matched to the SLIS arm according to gender, age, underlying disease, and date of diagnosis of cGVHD. All subjects were followed for one-year post treatment. The main outcome was incidence of each type of infection (event rate/ person-years). Kaplan Meier analysis was used, evaluating time to infection with log rank test. The spectrum of infectious complications was described. Results Seventy-seven patients were included (36 in ECP and 41 in SLIS arm). Median age was 57.4 years (18.1 -73.4), and 59.7% of patients were male. The most common underlying diseases were acute myeloid leukemia (45.4%), myelodysplastic syndrome (20.8%) and non-Hodgkin’s lymphoma (15.6%). A total occurrence of 94 infections was observed in the ECP arm, compared to 118 in SLIS arm. Bacterial infections accounted for majority of the infections in ECP arm (50%) compared to SLIS arm in which viruses were most common (49.2%). Bacterial pneumonia was the most common clinical syndrome (34% and 27.3%, in the ECP and SLIS arms, respectively). Bacteremia accounted for 12.8% of infections in the ECP arm compared to 16.4% in the SLIS arm. There was no difference in the event rates of infections among the two groups [2.58/ person-years in ECP group vs 3.60/person-years, p = 0.3766], or the probability of infection at any time between the ECP and SLIS group on Kaplan Meier (log rank test, p-value=0.36)(Figure 1). Kaplan-Meier plot of time to the earliest infection diagnosis between ECP and control group Conclusion Bacterial and viral pneumonia were the most common infections in patients undergoing ECP. Overall, ECP does not confer an increased risk of infectious complications compared to second line IS agents. Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

Extracorporeal photopheresis as second-line therapy for patients with acute graft-versus-host disease: does the number of cells treated matter?

Transfusion ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 1045-1053 ◽  
Author(s):  
Nina Worel ◽  
Elisabeth Lehner ◽  
Harald Führer ◽  
Peter Kalhs ◽  
Werner Rabitsch ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Second Line ◽  
Extracorporeal Photopheresis ◽  
Second Line Therapy ◽  
Host Disease ◽  
Graft Versus Host ◽  
Line Therapy ◽  
Number Of Cells ◽  
Acute Graft

scholarly journals Extracorporeal Photopheresis in Graft-versus-Host Disease

2020 ◽  
Vol 47 (3) ◽  
pp. 214-225 ◽  
Author(s):  
Beatrice Drexler ◽  
Andreas Buser ◽  
Laura Infanti ◽  
Gregor Stehle ◽  
Joerg Halter ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Second Line ◽  
Extracorporeal Photopheresis ◽  
Second Line Therapy ◽  
Host Disease ◽  
Graft Versus Host ◽  
Line Therapy ◽  
Therapy Option ◽  
Major Treatment ◽  
Patient Selection Criteria

Background and Summary: Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other diseases. Based on the substantial efficacy and the excellent safety profile in the absence of immunosuppression ECP has established itself as a major treatment form for steroid-refractory GvHD. Here we review the current literature on ECP as a treatment option for patients with aGvHD as well as cGvHD. Key Messages: ECP is a well-established second-line therapy for cGvHD. Its role in the treatment of aGvHD is less clear but also points towards an effective second-line therapy option. In the future ECP could play a role in the prevention of GvHD. More experimental and randomized controlled trials are needed to define the best patient selection criteria, settings, and therapy regimens for GvHD.

Extracorporeal Photopheresis Diminishes Graft-Versus-Host-Disease and Modulates Dendritic Cell Cytokine Production.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2177-2177
Author(s):  
Jessica P. Davis ◽  
Sarah Herby ◽  
Meghaan P. Walsh ◽  
Christian M. Capitini ◽  
Martin Guimond ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Weight Loss ◽  
Lymph Node ◽  
Graft Versus Host Disease ◽  
Cytokine Production ◽  
Extracorporeal Photopheresis ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Uva Light

Abstract Background: Graft-versus-host disease (GVHD) remains one of the largest obstacles in allogeneic stem cell transplantation. Current therapies for GVHD generally involve systemic immunosuppression resulting in increased risk of infection and relapse. Extracorporeal Photopheresis (ECP) is an emerging therapy for chronic GVHD that offers the potential of selective immunomodulation. In ECP, patient leukocytes are treated with 8-methoxypsoralen (8-MOP) and UVA light, causing them to undergo apoptosis, and are re-infused into the patient. Because ECP has been studied mostly in the clinical setting, however, the mechanism by which this infusion of apoptotic cells impacts GVHD remains unclear. We hypothesized that ECP-treated cells interact with recipient dendritic cells (DCs) to induce tolerance. We applied ECP to a murine GVHD model and explored the effects of ECP-treated cells on DCs. Methods: ECP: Splenocytes were incubated with 8-MOP at 200 ng/ml and exposed to UVA light (5 J/cm2). Bone Marrow Transplant (BMT): C3H.SW mice were irradiated (1000 cGy) and given 10 × 106bone marrow and 5 ×106 lymph node C57BL/6 (B6) cells on day 0. 10 ×106 ECP-treated splenocytes were administered on day 1. Co-culture: Female B6 BM-derived DCs were cultured for 7 days with GM-SCF and IL-4 and incubated overnight with untreated, irradiated (3000 cGy) or ECP-treated splenocytes. Anti-CD40 was used to activate DCs. DC phenotype and cytokine production were examined using flow cytometry. Vaccine: Male B6 DCs were co-incubated with untreated, irradiated or ECP-treated female B6 splenocytes and injected into naive female B6 recipients on days 14 and 28. On day 42, responses against the male histocompatibility antigen complex (H-Y) were assayed using IFN-gamma ELISPOT. Results: 85–94% of ECP-treated cells were Annexin+/7AAD+ 24 hours after ECP treatment. Infusion of ECP-treated cells diminished GVHD-associated weight loss regardless of the strain of the ECP donor (Fig. 1) and restored responsiveness to H-Y vaccination. In co-culture experiments, the presence of ECP-treated cells did not alter phenotypic maturation of DCs. However, co-culture of DCs with ECP-treated cells did alter DC cytokine production resulting in less IL-12 production when compared to anti-CD40 alone (1.0% vs. 4.2% of CD11b+/CD11c+ cells). Finally, immunization of naive female mice with male DCs co-cultured with ECP-treated cells resulted in a modest but statistically significant (p=.0499) decrease in subdominant, class I H-Y responses compared to DCs incubated with untreated splenocytes. Conclusion: The administration of ECP-treated cells in vivo appears to lessen the severity of GVHD, allowing mice to maintain immunocompetence. DCs cultured in the presence of ECP-treated cells can mature phenotypically but exhibit altered cytokine production. Activated, co-incubated DCs are less potent when used as a vaccine. This data suggests that perhaps the alteration of recipient DCs may contribute to the beneficial effect of ECP in GVHD. Ongoing experiments continue to explore the role of recipient DCs in ECP treatment of GVHD. Figure 1. Female C3.HSW mice were lethally irradiated and received 10 × 106 bone marrow and 5 × 106 lymph node C57BL/6 (B6) cells on Day 0. On Day 1, 10 × 106 ECP-treated cells from either recipient (C3.HSW), donor (B6) or 3rd Party (BALB.B) mice were administered. Weight loss was monitored twice weekly. Figure 1. Female C3.HSW mice were lethally irradiated and received 10 × 106 bone marrow and 5 × 106 lymph node C57BL/6 (B6) cells on Day 0. On Day 1, 10 × 106 ECP-treated cells from either recipient (C3.HSW), donor (B6) or 3rd Party (BALB.B) mice were administered. Weight loss was monitored twice weekly.

scholarly journals Outcomes of Extracorporeal Photopheresis (ECP) in Treatment of Severe Acute Graft-Versus-Host Disease (aGvHD)

2021 ◽  
Vol 27 (3) ◽  
pp. S297-S298
Author(s):  
Zachary J Sebghati ◽  
Haitham Abdelhakim ◽  
Anurag K Singh ◽  
Leyla Shune ◽  
Siddhartha Ganguly ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Extracorporeal Photopheresis ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

scholarly journals 1075. Absolute Lymphocyte Count as a Predictor of Cytomegalovirus (CMV) Infection and Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S565-S565
Author(s):  
Joanne Reekie ◽  
Marie Helleberg ◽  
Christina Ekenberg ◽  
Mark P Khurana ◽  
Isabelle P Lodding ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Abstract Background Cytomegalovirus (CMV) is a serious complication following Hematopoietic Stem Cell Transplant (HSCT) and can lead to serious organ disease and mortality. This study aimed to investigate the association between absolute lymphocyte count (ALC) and CMV to determine whether ALC could help to identify those at an increased risk of CMV infection and recurrence Methods Adults undergoing HSCT between 2011 and 2016 at Rigshospitalet, Denmark were included. Cox proportional hazards models investigated risk factors, including ALC, for CMV infection in the first year post-transplant and recurrent CMV infection 6 months after clearance and stopping CMV treatment for the first infection. For the primary outcome ALC was investigated as a time-updated risk factor lagged by 7 days, and for recurrent CMV, ALC measured at the time at the time of stopping treatment for the first CMV infection was investigated (+/- 7 days). Results Of the 352 HSCT recipients included, 57% were male, 40% received myeloablative conditioning, 42% had high risk (D-R+) CMV IgG serostatus at transplant and the median age was 56 (IQR 43-63). 143 (40.6%) patients had an episode of CMV DNAemia a median of 47 days after transplant (IQR 35-62). A lower current ALC (≤ 0.3 x109/L) was associated with a higher risk of CMV infection in univariate analysis compared to a high current ALC (> 1 x109/L). However, this association was attenuated after adjustment, particularly for acute graft versus host disease (Figure). 102 HSCT recipients were investigated for risk of recurrent CMV of which 41 (40.2%) had a recurrent CMV episode a median of 27 days (IQR 16-50) after stopping CMV treatment for the first infection. A lower ALC (≤ 0.3 x109/L) at the time of stopping CMV treatment was associated with a significantly higher risk of recurrent CMV after adjustment (Figure). A higher peak viral load (> 1500 IU/ml) during the first episode of CMV infection was also associated with an increased risk of recurrent CMV (aHR 2.47, 95%CI 1.00-6.10 compared to < 750 IU/ml). Association between absolute lymphocyte count (ALC) and risk of CMV infection and recurrent CMV within 6 months. **First CMV infection multivariable model also adjusted for sex, CMV serostatus, age, year of transplant, Charlson Comorbidity Index, Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease (time-updated) *Recurrent CMV infection multivariable model also adjusted for conditioning regimen, sex, CMV serostatus, age, year of transplant Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease and peak CMV viral load during the first CMV infection Conclusion A lower ALC at the time of stopping treatment for the first CMV infection was associated with an increased risk of recurrent CMV and could be used to help guide decisions for augmented CMV surveillance and clinical awareness of CMV disease symptoms in these patients. Disclosures All Authors: No reported disclosures

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