Low Absolute CD4 Central Memory Count On Day 30 Is Associated with An Increased Incidence of Chronic Graft-Versus-Host Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 516-516
Author(s):  
Zachariah A. McIver ◽  
Andrew Grim ◽  
Nicolas Naguib ◽  
A. John Barrett
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Central Memory ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Abstract 516 Early lymphocyte recovery is an important determinant of hematopoietic stem cell transplant (SCT) outcome. We found that robust day 30 lymphocyte counts are associated with a decreased incidence of relapse, decreased rates of both acute and chronic graft-versus-host disease (a-GvHD, c-GvHD), and increased survival. Natural killer (NK) cells contribute to lymphocyte recovery and may be associated with a strong graft-versus-leukemia and anti-GvHD effect. However, the contribution of the recovery of specific T cell subsets to transplant outcome has not been fully explored. We studied 43 patients undergoing a myeloablative matched-sibling T-cell depleted or selectively depleted SCT for a variety of hematological malignancies including AML, ALL, CML, and MDS. Median age was 43 years (range, 13–68), and median CD34 cell dose was 6.1×106/kg (range, 3.1-10.1). Thirty-one patients developed a-GvHD (12 grade I, 18 grade II, 1 grade II). Twelve patients had c-GvHD (7 limited, 5 extensive). On day 30 after SCT a peripheral blood sample was collected on all patients and cryopreserved. In preparation for analysis, mononuclear cells from these samples were thawed and rested overnight. Flow cytometry was then performed on a BD FACS CantoII flow cytometer with multicolor fluorochrome antibodies to CD3, CD4, CD8, CD27, and CD45RO. Subsets were defined as follows: Naive (N) CD27+CD45RO-, Central Memory (CM) CD27+CD45RO+, Effector Memory (EM) CD27-CD45RO+, and Effectors (E) CD27-CD45RO-. Data was analyzed by BD FACSDiva software, and Kaplan-Meier survival statistical analysis was performed on the readouts. Median subset frequencies were CD3+: 254 /μL (range, 75-2085), CD4+ : 132 /μL (range, 3-501), CD8+ :101 /μL (range, 9-1361), CD4+ EM 49/μL (range, 2-252), CD4+CM 60/μL (range, 1-253), CD8+ EM: 50 cells/μL (range 2-977), CD8+ CM 28 /μL (range, 2-401), Naïve and Effector cells were minimally or non-detected in both CD4+ and CD8+ compartments. When T cell subset recovery was correlated with transplant outcomes (a-GVHD, c-GVHD, relapse and survival) one significant association was identified: low CD4+ CM counts correlated with a higher incidence of c-GvHD. Patients that had less than the median value of 60 CD4+ CM cells/μL had a significantly higher likelihood of developing c-GvHD (HR 4.28, p=0.039, see figure). Additionally, when considering degree of disease, low CD4+ CM counts were associated with the severest manifestations of c-GvHD (p=0.021). As a result, we conclude that low absolute concentrations of CD4+ CM cells on day 30 after SCT reflects a deficiency in regulatory mechanisms important in the control of alloreactivity, and may be used as a surrogate marker for individuals at risk of developing c-GvHD. Disclosures: No relevant conflicts of interest to declare.

Dendritic cell–activated CD44hiCD8+ T cells are defective in mediating acute graft-versus-host disease but retain graft-versus-leukemia activity

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3970-3978 ◽  
Author(s):  
Yi Zhang ◽  
Gerard Joe ◽  
Jiang Zhu ◽  
Richard Carroll ◽  
Bruce Levine ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Graft Versus Host Disease ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Antitumor Effects ◽  
Host Disease ◽  
Graft Versus Host

Abstract Graft versus host disease (GVHD) is triggered by host antigen-presenting cells (APCs) that activate donor T cells to proliferate and differentiate, but which APC-activated donor T-cell subsets mediate GVHD versus beneficial antitumor effects is not known. Using a CD8+ T cell–dependent mouse model of human GVHD, we found that host dendritic cell (DC)–induced CD44hiCD8+ effector/memory T cells were functionally defective in inducing GVHD, whereas CD44loCD8+ naive phenotype T cells were extremely potent GVHD inducers. Depletion of CD44loCD8+ T cells from host DC-stimulated T cells before transplantation prevented GVHD without impairing their antitumor activity in vivo. Compared with CD44loCD8+ T cells, CD44hiCD8+ T cells expressed high levels of Fas and were efficiently deleted in vivo following transplantation. These results suggest that ex vivo allogeneic DC stimulation of donor CD8+ T cells may be useful for the prevention of GVHD and for optimizing antitumor therapies in vivo.

scholarly journals In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 1113-1122 ◽  
Author(s):  
Andreas Beilhack ◽  
Stephan Schulz ◽  
Jeanette Baker ◽  
Georg F. Beilhack ◽  
Courtney B. Wieland ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Lymphoid Organs ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Host Disease ◽  
Graft Versus Host ◽  
Secondary Lymphoid Organs

AbstractGraft-versus-host disease (GVHD) is a major obstacle in allogeneic hematopoietic cell transplantation. Given the dynamic changes in immune cell subsets and tissue organization, which occur in GVHD, localization and timing of critical immunological events in vivo may reveal basic pathogenic mechanisms. To this end, we transplanted luciferase-labeled allogeneic splenocytes and monitored tissue distribution by in vivo bioluminescence imaging. High-resolution analyses showed initial proliferation of donor CD4+ T cells followed by CD8+ T cells in secondary lymphoid organs with subsequent homing to the intestines, liver, and skin. Transplantation of purified naive T cells caused GVHD that was initiated in secondary lymphoid organs followed by target organ manifestation in gut, liver, and skin. In contrast, transplanted CD4+ effector memory T (TEM) cells did not proliferate in secondary lymphoid organs in vivo and despite their in vitro alloreactivity in mixed leukocyte reaction (MLR) assays did not cause acute GVHD. These findings underline the potential of T-cell subsets with defined trafficking patterns for immune reconstitution without the risk of GVHD.

scholarly journals Correlation of T Cell Subsets and Hypercholesterolemia of the Donor and Its Association with Acute Graft-versus-Host Disease

2019 ◽  
Author(s):  
MM Rivera-Franco ◽  
Eucario León-Rodríguez ◽  
Diana Gómez-Martín
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Inflammatory Responses ◽  
T Cell Subsets ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor Bone Marrow ◽  
A Prospective Study ◽  
Acute Graft

Background: Acute graft-versus-host disease (aGVHD) is an important cause of death following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The association between cholesterol and aGVHD was previously described potentially resulting from pro-inflammatory responses associated with hypercholesterolemia. The aim of this study was to correlate T-cell subsets in donor bone marrow (BM) samples with their levels of cholesterol and associate these results with recipients who developed aGVHD and those who did not. Materials and Methods: A prospective study was performed in 39 donor samples. T-cell subsets were analyzed by flow cytometry. Results: Eleven (28%) donors had hypercholesterolemia. Donor samples with hypercholesterolemia had less Tregs compared to donors with normal levels of cholesterol (22.69 (IQR=30.6) cells/µL vs 52.62 (IQR=44.68) cells/µL, p=0.04). Among all individuals in the cohort, aGVHD was observed in 21%: 36% from donors with hypercholesterolemia versus 14% from donors with normal levels of cholesterol. Conclusion: As we described the association between hypercholesterolemia and diminished Tregs, our results might suggest that normalizing the levels of total cholesterol in the donor, prior performing allo-HSCT, might be an effective approach to diminish the risk of the receptor to develop aGVHD.

scholarly journals Impact of High Donor-Derived CD4+ CCR7+ T Cell Count on Incidence of Grade II-IV Acute Graft-Versus-Host Disease Following Haploidentical Hematopoietic Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5721-5721
Author(s):  
Pauline Varlet ◽  
Tamim Alsuliman ◽  
Jacques Trauet ◽  
Julie Demaret ◽  
Myriam Labalette ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Memory T Cells ◽  
T Cell Subsets ◽  
Host Disease ◽  
Graft Versus Host ◽  
Central Memory T Cells ◽  
Grade Ii ◽  
Acute Graft

Abstract Introduction Historically the administration of post-transplant high-dose Cyclophosphamide (PTCy) has led to haplo-HCT re-innovation. Although PTCy has a positive impact towards reducing severe acute graft-versus-host disease (aGVHD), this drug has serious adverse side effects and makes haploidentical-HCT more difficult in some patients-particularly in older patients and/or those presenting other comorbidities. Considering our previous published experience in the effect of graft lymphocyte composition, this work aims to explore the impact of infused T cell subsets on Overall Survival (OS), Event Free Survival (EFS) and acute GVHD in a retrospective cohort receiving allogeneic haplo-HCT. Methods This study retrospectively analyzed 29 adult patients who underwent first allogeneic haplo-HCT for hematologic malignancies at Lille University Hospital (CHRU Lille, France). Graft samples were analyzed by flow cytometry, and CD4 and CD8 T cell subsets were defined as follows: TN=naïve T cells; , TCM=central memory T cells; TEM=effector memory T cells; TTD =terminally differentiated T cells. Results The median follow-up of patients was 11 months (0.4-44.3). The cohort median recipient age was 59 years old. Cumulative incidences of grade 2 to 4 aGVHD were 31%. The rate of grade 3 to 4 severe GVHD was 17%. Eleven patients died with 14% of deaths due to non-relapse mortality. We found a correlation between high percentage of donor-derived CD4+ CCR7+ T cells (>69.2% for CD4+ T cells-the median value in our study) and aGVHD (p=0.028) without any impact on OS and EFS (Table 1). In multivariate analysis, only high proportions of donor CD4+ CCR7+ T cells correlated significantly with aGVHD (HR=0.203, 95% CI [0,042-0,980], p=0,047) without any impact on OS and EFS (Figure 1). Conclusion Naïve and central memory T cells expressing CCR7 exhibit higher alloreactivity potential than CCR7- T cells. In this study, even with PTCy administration, we observed that a high percentage of donor-derived CD4+ CCR7+ T cells can be considered as a predictive indicator of grade II-IV aGVHD post Haplo-HCT. Thus, selective depletion of CD4+ CCR7+ T cells might be enough to prevent aGVHD in haplo-HCT, enabling the use of low doses of PTCy in order to reduce post haplo-HCT complications. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2476-2484 ◽  
Author(s):  
Hong Zheng ◽  
Catherine Matte-Martone ◽  
Hongmei Li ◽  
Britt E. Anderson ◽  
Srividhya Venketesan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Myelogenous Leukemia ◽  
Effector Memory ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Graft Versus Leukemia ◽  
Donor T Cells

Much of the efficacy of allogeneic hematopoietic stem cell transplantation (alloSCT) in curing hematologic malignancies is due to a graft-versus-leukemia (GVL) effect mediated by donor T cells that recognize recipient alloantigens on leukemic cells. Donor T cells are also important for reconstituting immunity in the recipient. Unfortunately, donor T cells can attack nonmalignant host tissues and cause graft-versus-host disease (GVHD). We previously reported that donor CD4+ effector memory T cells (TEMs) do not cause GVHD but transfer functional T-cell memory. In the present work, we demonstrate in an MHC-mismatched model that CD4+ TEMs (unprimed to recipient antigens) mediate GVL against clinically relevant mouse models of chronic phase and blast crisis chronic myelogenous leukemia, without causing GVHD. By creating gene-deficient leukemias and using perforin-deficient T cells, we demonstrate that direct cytolytic function is essential for TEM-mediated GVL, but that GVL is retained when killing via FasL, TNF-α, TRAIL, and perforin is individually impaired. However, TEM-mediated GVL was diminished when both FasL and perforin pathways were blocked. Taken together, our studies identify TEMs as a clinically applicable cell therapy for promoting GVL and immune reconstitution, particularly in MHC-mismatched haploidentical alloSCTs in which T cell–depleted allografts are commonly used to minimize GVHD.

scholarly journals Alemtuzumab Versus Anti-Thymocyte Globulin As Conditioning Method for Allogenic Hematopoietic Stem Cell Transplant; A Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Kittika Poonsombudlert ◽  
Jakrin Kewcharoen ◽  
Chattip Prueksapraopong ◽  
Limpruttidham Nath
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Objective: Anti-thymocyte Globulin (ATG) and Alemtuzumab (Ale) are common methods for T cell depletion in the setting of allogenic hematopoietic stem cell transplant. They are both used to promote engraftment and prevent graft-versus-host disease (GVHD). Currently, there's no comparative meta-analysis for safety and efficacy of Ale versus ATG. Therefore, we conducted a meta-analysis to compare the risk of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), odd of relapse and overall survival (OS) between Ale and ATG. Method: We performed a comprehensive literature search in MEDLINE (Pubmed), Cochrane library and EMBASE database from inception to April 2020 for studies that compared the use of Ale and ATG. We conducted a random effect meta-analysis of 11 studies involving a total of 4,239 participants (Ale=1,293, ATG=2,946) and reported the pooled odd ratio (OR) for development of aGVHD, cGVHD, relapse and OS. Result: We found a significant decreased in odd of aGVHD and cGVHD in the Ale group compared to the ATG group (pooled OR 0.44, 95% CI 0.32-0.61, I2=56.1% and 0.58, 95% CI 0.44-0.77, I2=47.5% respectively) but there were no statistically significant increase in the odd of relapse and OS (pooled OR 1.14, 95% CI 0.81-1.59, I2=64.5% and 1.20, 95% CI 0.83-1.72, I2=76.3% respectively). Conclusion: There is significantly decreased odd of aGVHD and cGVHD with use of Ale compared to ATG, but there is no statistically significant increased odd of relapse or OS. We concluded that Ale could be the superior method of T cell depletion in terms of decreased aGVHD and cGVHD but there's no significant difference in odd of relapse and OS. Disclosures No relevant conflicts of interest to declare.

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 A Novel Secondary Neoplasm Following Allogeneic Hematopoietic Stem Cell Transplant: Mixed Donor-Recipient Primitive Mesenchymal Proliferation of the Liver

2021 ◽  
pp. 109352662110016
Author(s):  
Brian Earl ◽  
Zi Fan Yang ◽  
Harini Rao ◽  
Grace Cheng ◽  
Donna Wall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Post Transplant

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.

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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