scholarly journals Expression of the Chemokine Receptor CCR5 on Blood CD11C+ CD16+ Dendritic Cells Post-Allogeneic Hemopoietic Cell Transplant is Predictive for the Development of Acute Graft Versus Host Disease

2011 ◽  
Vol 17 (2) ◽  
pp. S341
Author(s):  
K. Shanin ◽  
M. Sartor ◽  
D.N.J. Hart ◽  
K.F. Bradstock
Keyword(s):  
Dendritic Cells ◽  
Graft Versus Host Disease ◽  
Chemokine Receptor ◽  
Cell Transplant ◽  
Hemopoietic Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Chemokine Receptor Ccr5 ◽  
Receptor Ccr5 ◽  
Acute Graft

Upregulation of the Chemokine Receptor CCR5 on CD16+ Myeloid Blood Dendritic Cells in Allogeneic Hemopoietic Cell Transplant Patients Predicts for Acute Graft Versus Host Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1982-1982 ◽  
Author(s):  
Kifah Shahin ◽  
Mary M Sartor ◽  
Derek NJ Hart ◽  
Kenneth F Bradstock
Keyword(s):  
Dendritic Cells ◽  
Graft Versus Host Disease ◽  
Chemokine Receptor ◽  
Acute Gvhd ◽  
Hemopoietic Cell ◽  
Ccr5 Expression ◽  
Graft Versus Host ◽  
Chemokine Receptor Ccr5 ◽  
Receptor Ccr5 ◽  
Acute Graft

Abstract Abstract 1982 Introduction: Dendritic cells (DC) are centrally involved in the development of acute graft-versus-host disease (GvHD) following allogeneic hemopoietic cell transplantation (alloHCT). We previously showed that the activation status, as assessed by CMRF-44 antigen expression, of CD11c+ myeloid blood DC is highly associated with the onset and severity of acute GvHD (Transplantation. 2007;83:839–846). We also reported a positive correlation between acute GvHD and the expression of the chemokine receptor CCR5 on CD11c+ myeloid DC (Blood. 2009;114 Suppl.:2251). Given the phenotypic and functional heterogeneity of the CD11c+ DC population, we investigated CCR5 expression on the CD11c+ DC subsets and then monitored the informative CD11c+ CD16+ DC subset expression of CCR5 in the peripheral blood of 42 patients post alloHCT, and correlated the findings with GvHD. Methods: Peripheral blood was collected twice weekly up to Day 100 post transplant from 42 alloHCT patients. The expression of CCR5 receptor on CD11c+ and CD11c- DC subsets was evaluated using multiparameter flow cytometry. Results: Only the CD11c+ CD16+ DC subset lacked CCR5 and induced it upon alloactivation. Seventeen of 42 patients developed acute GvHD (5 grade I, 12 grades II-IV). The percentage of CD11c+ CD16+ DC expressing CCR5 correlated with the development of acute GvHD grades II-IV. The maximum CCR5 expression detected on CD11c+ CD16+ DC in patients prior to developing grades II-IV GvHD (mean 22.7 ± 4.3%, n=12) was higher than in those with grades 0-I GvHD (11.4 ± 1.7%, n=30) (p=0.0285). CCR5 levels >20% on CD16+ myeloid DC predicted grades II-IV GvHD with a sensitivity of 66.7% and specificity of 86.7%. Levels of expression of CCR5 on the CD11c+ CD16- DC and CD123+ plasmacytoid DC were not predictive of GvHD. Conclusion: Expression of CCR5 on circulating CD11c+ CD16+ myeloid DC post alloHCT correlated with the development of moderate to severe GvHD. This observation may reflect DC activation or altered DC homing during the alloimmune response. Detection of increased CCR5+ CD11c+ CD16+ DC may allow pre-emptive therapeutic intervention prior to the clinical diagnosis of GvHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Chemokine Receptor CCR5 Mediates AlloImmune Responses in Graft-versus-Host Disease

2010 ◽  
Vol 16 (3) ◽  
pp. 311-319 ◽  
Author(s):  
Lisa A. Palmer ◽  
George E. Sale ◽  
John I. Balogun ◽  
Dan Li ◽  
Dan Jones ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chemokine Receptor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Chemokine Receptor Ccr5 ◽  
Receptor Ccr5

scholarly journals Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 613
Author(s):  
Nidhi Sharma ◽  
Qiuhong Zhao ◽  
Bin Ni ◽  
Patrick Elder ◽  
Marcin Puto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Tacrolimus Concentration ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
The Impact ◽  
Risk Of Relapse ◽  
Acute Graft

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

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

scholarly journals Blood dendritic cells are decreased in acute graft-versus-host disease

2004 ◽  
Vol 33 (10) ◽  
pp. 989-996 ◽  
Author(s):  
M Takebayashi ◽  
R Amakawa ◽  
K Tajima ◽  
M Miyaji ◽  
K Nakamura ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Impact of clostridiodes difficile infection on acute graft-versus-host disease in allogenic transplant patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19027-e19027
Author(s):  
Prasanth Lingamaneni ◽  
Vatsala Katiyar ◽  
Rohit Kumar ◽  
Maha A.T. Elsebaie ◽  
Hashim Mann ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphoblastic Leukemia ◽  
Index Admission ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Hospitalization Costs ◽  
Acute Graft

e19027 Background: Clostridiodes difficile infection (CDI) is reported to occur up to 9-fold higher in allogenic hematopoietic stem cell transplant (HSCT) recipients compared to the general population of hospitalized patients. This is attributed to disruption of gut microbiome by antibiotics, myeloablative regimens, neutropenia, prolonged hospitalization, and immunosuppressive regimens administered to prevent acute graft-versus-host disease (aGVHD). CDI by disruption of the intestinal microbiome may trigger gastrointestinal aGVHD. Previous studies from HSCT centers have reported conflicting data on the relationship between CDI and subsequent development of aGVHD. Methods: The Nationwide Readmissions Database was queried for admissions of adult allogenic HSCT patients between 2016 and 2018. Those with and without CDI during index admission were compared. Multivariable logistic regression was used to evaluate the primary outcome of risk of aGVHD in the index admission or within 100 days post-engraftment. Results: A total of 13518 allogenic HSCT patients were included in the study. Mean age was 52.4 years. 57.2% of patients were female. The most common underlying diagnoses were acute myeloid leukemia (38%), myelodysplastic syndrome (17%) and acute lymphoblastic leukemia (14%). 11.1% of the index admissions were complicated by CDI. Rates of aGVHD during the index admission or 100 days post-engraftment were similar between CDI and non-CDI groups: 13.8% vs. 12.1%, p=0.19 during index admission and 29.2% vs. 26.1%, p=0.09 during 100 days post-engraftment. Nonetheless, patients with CDI had longer length of hospital stay (34.6 vs 29.8 days, p<0.0001), higher hospitalization costs ($608K vs $506K USD) and greater rate of inpatient mortality (7.3% vs 4.6%, p<0.001). In the multivariate regression analysis, CDI during index admission was not associated with risk of development of aGVHD (Adjusted Odds Ratio 1.14, 95% Confidence Interval 0.87-1.48, p=0.34). Age and unrelated donor HSCT were predictive of risk of aGVHD. Conclusions: CDI during index admission was not predictive of aGVHD during the first 100 days post-allogenic HSCT. HSCT patients are frequency colonized with C.difficile. Diarrhea secondary to CDI may resemble gastrointestinal aGVHD. Therefore, overdiagnosis of CDI in this population is a concern. Antimicrobial stewardship and use of clinical decision support tools have been advocated recently to decrease testing of HSCT patients with C.difficile colonization. Multivariable analysis of risk factors of aGVHD.[Table: see text]

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