scholarly journals CCR5 Expression On Circulating Blood DC Post-Allogeneic Hemopoietic Cell Transplant Is Highly Predictive For The Development Of Clinically Significant Acute Graft Versus Host Disease

2010 ◽  
Vol 16 (2) ◽  
pp. S163 ◽  
Author(s):  
M.M. Sartor ◽  
J. Lau ◽  
D.J. Gottlieb ◽  
K.F. Bradstock
Keyword(s):  
Graft Versus Host Disease ◽  
Cell Transplant ◽  
Hemopoietic Cell ◽  
Ccr5 Expression ◽  
Host Disease ◽  
Graft Versus Host ◽  
Clinically Significant ◽  
Acute Graft

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

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]

scholarly journals Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow

Blood ◽  
1984 ◽  
Vol 63 (6) ◽  
pp. 1265-1270 ◽  
Author(s):  
DS Bross ◽  
PJ Tutschka ◽  
ER Farmer ◽  
WE Beschorner ◽  
HG Braine ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Predictive Parameters ◽  
Clinically Significant ◽  
Mismatched Donor ◽  
Acute Graft

Abstract To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.

scholarly journals Expression of Serum Micrornas Are Dysregulated during Acute Graft Versus Host Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5715-5715
Author(s):  
Rachel E Crossland ◽  
Jean Norden ◽  
Mateja Kralj Juric ◽  
Kile Green ◽  
Kim F Pearce ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Roc Analysis ◽  
Microrna Expression ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Diagnostic Ability ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft ◽  
Independent Cohort

Abstract Introduction MicroRNAs are expressed in body fluids and have recently been associated with the etiology of acute graft versus host disease (GvHD), but global expression profiling in a haematopoietic stem cell transplant (HSCT) setting is lacking. An improved understanding of the molecular pathogenesis of aGvHD may allow for improved therapeutic options, or guide personalised prophylactic protocols. Methods Mature microRNA serum expression (n=799) was assessed using nCounter technology (NanoString) in a training cohort of diagnostic aGvHD samples (n=12). Analysis assessed for microRNAs that were dysregulated in patients who developed aGvHD compared to no aGvHD. Signature microRNAs were validated in an independent cohort of serum samples taken at aGvHD diagnosis (n=42) and prior to disease onset (day 14 (D14) post-HSCT, n=47). Results NanoString profiling identified 61 microRNAs that were differentially expressed at aGvHD onset, of which n=27 were downregulated (fold change (FC) -6.94 - -1.75; p<0.01 - p=0.048) in aGvHD while n=34 were upregulated (FC 1.35 - 5.41; p<0.01 - p=0.046). 10 microRNAs (miR-146a, miR-30b, miR-374, miR-20a, miR-15a, miR-181a, miR-18a, miR-19a, miR-19b and miR-451a) were selected for further assessment in an independent diagnostic cohort (n=42), based on high FC or those reported in the literature to be implicated in GvHD, T-cell function or the inflammatory response. MiR-146a (p=0.03), miR-30b-5p (p=0.007), miR-374-5p (p=0.02) and miR-181a (p=0.03) were significantly downregulated, whilst miR-20a (p=0.03) and miR-15a (p=0.03) were significantly upregulated in aGvHD. MiR-30b (AUC=0.75, p=0.007), miR-374-5p (AUC=0.74, p=0.01) and miR-15a (AUC=0.70, p=0.04) had diagnostic ability for aGvHD as assessed by receiver operator characteristic (ROC) analysis, whilst miR-181 (AUC=0.68, p=0.06), miR-146a (AUC=0.66, p=0.09) and miR-20a (AUC=0.68, p=0.06) were approaching significance. There was no significant difference in microRNA expression between clinical factors including transplant relationship, patient gender or conditioning regimen, indicating the effect to be related to aGvHD incidence. MicroRNA expression was also assessed at D14 post-HSCT in an independent cohort (n=47) to investigate their prognostic marker potential. MiR-146a (p=0.01), miR-20a (p=0.03), miR-18a (p=0.03), miR-19a (p=0.03), miR-19b (p=0.02) and miR-451 (p=0.01) were expressed at significantly higher levels in patients who developed aGvHD vs. no aGvHD. In ROC analysis, miR-146a (A=0.68, p=0.03), miR-19b (A=0.70, p=0.02) and miR-451 (A=0.69, p=0.03) had diagnostic ability with regards to aGvHD incidence, whilst miR-18a (A=0.65, p=0.09), miR-19a (A=0.65, p=0.08) and miR-20a (A=0.67, p=0.06) were approaching significance. Conclusions Circulating microRNAs have the capacity to act as prognostic and diagnostic biomarkers for aGvHD and might assist in developing personalised therapeutic approaches. Their dysregulated expression suggests a role in aGvHD pathology, which warrants further investigation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Letermovir Prophylaxis and Cytomegalovirus Reactivation in Adult Hematopoietic Cell Transplant Recipients with and without Acute Graft Versus Host Disease

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5572
Author(s):  
Delaney Wolfe ◽  
Qiuhong Zhao ◽  
Emma Siegel ◽  
Marcin Puto ◽  
Danielle Murphy ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Control Group ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Host Disease ◽  
Graft Versus Host ◽  
Clinically Significant ◽  
Cmv Reactivation

Cytomegalovirus (CMV) is the most clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that can further increase CMV infection risk. Prophylaxis with letermovir, an oral antiviral approved to prevent CMV, has been shown to decrease the incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation, but there is a lack of data confirming this benefit in patients with GVHD. In this single-center, retrospective study, we assessed the incidence of clinically significant CMV infection (CS-CMVi) in allo-HCT patients who received letermovir prophylaxis (n = 119) and who developed aGVHD compared to a control group (n = 143) who did not receive letermovir. Among aGVHD patients, letermovir prophylaxis decreased CS-CMVi in patients with aGVHD (HR 0.08 [95% CI 0.03–0.27], p < 0.001), reduced non-relapsed mortality (p = 0.04) and improved overall survival (p = 0.04). This data suggests that letermovir prophylaxis improves outcomes by preventing CS-CMVi in patients with aGVHD.

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