Risk Factor Analysis for Predicting Chronic Graft-Versus-Host Disease of Progressive or Quiescent Type in a Cohort of Patients with a History of Acute Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5337-5337
Author(s):  
Sang Kyun Sohn ◽  
Dong Hwan Kim ◽  
Jin Ho Baek ◽  
Jong Gwang Kim ◽  
Kyu Bo Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Clinical Parameters ◽  
Host Disease ◽  
Graft Versus Host ◽  
History Of

Abstract Background: As a series of our previous investigation (Haematologica, 2005. 90: 939–48) identifying poor prognostic factors (lymphocytopenia and visceral involvement) at the onset of acute GVHD (aGVHD) in patients with a history of aGVHD after allogeneic stem cell transplantation (SCT), we tried to identify variables that could predict the development of chronic GVHD of progressive or quiescent type (pq cGVHD) and patients’ outcome after the diagnosis of cGVHD in cohort of 99 patients who experienced aGVHD after allogeneic SCT. Patients and Methods: We evaluated the risk factors for cGVHD of pq cGVHD with various clinical parameters in patient group with a history of aGVHD and also the prognostic significance of various clinical parameters at diagnosis of cGVHD to determine the prognostic factor for GVHD-specific survival (GSS) in patients with pq cGVHD. Results: From 118 patient experienced aGVHD of any degree, 99 patients were evaluated for cGVHD. The cumulative incidence of overall and extensive pq cGVHD at 2 years was estimated as 84.4% and 63.1%, respectively. In univariate analyses for risk factors of pq cGVHD, severe grade 3,4 aGVHD, primary treatment failure (PTF), lymphocytopenia (≤100/μl), elevated ALP (>160IU/l), visceral involvement, hepatic or gut involvement were identified. Especially, severe aGVHD (p=0.022 and <0.001), PTF (p=0.009 and 0.010) for overall and extensive pq cGVHD, lymphocytopenia (p=0.031) for extensive pq cGVHD, and elevated ALP (p=0.001) for overall pq cGVHD were independent risk factors. The prediction model of subsequent pq cGVHD validated these risk factors with respect to the incidences of overall pq cGVHD (48.6% versus 91.9% for no risk factor versus 1~3 risk factor(s)) and of extensive pq cGVHD (34.2% versus 59.6% versus 92.2% for no / 1 / 2~3 risk factors). HLA-disparity and stem cell source did not influence on the development of pq cGVHD in this cohort. The GSS and probability of systemic immunosuppressive treatment at 2 year after diagnosis of cGVHD was estimated as 55.9% and 51.9%. The GSS was significantly associated with the performance status (p=0.004) and lymphocytopenia (≤ 1,000/μl, p=0.022) at diagnosis of cGVHD by Cox’s proportional hazard model. Conclusion: Severe aGVHD, PTF, lymphocytopenia and elevated ALP may be useful predictive factors for the development of pq cGVHD in a cohort of patients who experienced a GVHD after allogeneic SCT. Figure. The significance of the predictive model for the development of overall (A) or extensive chronic graft-versus-host disease (GVHD; B) after occurence of acute GVHD Figure. The significance of the predictive model for the development of overall (A) or extensive chronic graft-versus-host disease (GVHD; B) after occurence of acute GVHD

A Possible Association between the Presence of Interleukin-4-Secreting Cells and a Reduction in the Risk of Acute Graft-Versus-Host Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4968-4968
Author(s):  
Maki Takabayashi ◽  
Heiwa Kanamori ◽  
Hirotaka Takasaki ◽  
Satoshi Yamaji ◽  
Hideyuki Koharazawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Interleukin 4 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract We monitored interleukin-4 (IL-4), interferon-gamma (IFN-g), and tumor necrosis factor alpha (TNF-a)-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation. Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from before the preconditioning regimen to 56 days after transplantation. The frequency of IL-4-secreting cells was significantly higher in 5 patients receiving peripheral blood stem cell transplantation (PBSCT) than that in 18 patients who received bone marrow transplantation (BMT). Based on IFN-g and TNF-a release, there was a trend toward a decrease in the number of cytokine-secreting cells in PBSCT. Furthermore, patients who did not develop acute graft-versus-host disease (GVHD, n = 5) showed a significantly higher number of IL-4-secreting cells compared with those who developed acute GVHD (n = 18). These results indicate that the high percentage of IL-4-secreting cells may be responsible for the inhibition of acute GVHD. In addition, the increased percentage of IL-4-secreting cells may be responsible for the unexpected low incidence of acute GVHD in PBSCT, despite the presence of large numbers of mature T cells in the donor infusion.

Graft Versus Host Disease (GVHD) Prophylaxis with Everolimus and Tacrolimus Is Associated with a High Incidence of Sinusoidal Obstruction Syndrome and Microangiopathy – Results of the EVTAC Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1172-1172
Author(s):  
Uwe Platzbecker ◽  
Malte Bonin ◽  
Eray Goekkurt ◽  
Joergen Radke ◽  
Alexander Kiani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Prophylactic Regimen ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

Abstract Beyond disease biology, the success of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematological malignancies is mainly determined by the occurrence and extent of graft versus host disease (GVHD). Therefore, prevention of GVHD is the major goal and challenge in clinical HSCT. A calcineurin-inhibitor combined with methotrexate is the standard graft versus host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus is a derivative of sirolimus, which also seems to mediate anti-leukemia effects. Given the potential synergism and favourable toxicity profile of everolimus and tacrolimus (EVTAC) after allogeneic HSCT we sought to investigate the efficacy of this combination in patients with either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). We report a combination of everolimus (days 0–56) and Tacrolimus (from day −1 on) in 24 patients (pts, median age 62 years) with either MDS (n=17) or AML (n=7) undergoing intensive busulfan-based conditioning followed by HSCT from related (n=4) or unrelated matched (n=12) or 1-allele mismatched (n=8) donors. All pts engrafted and only one experienced grade IV mucositis. However, although everolimus was scheduled to be administered up to day 56, patients received the drug a median of 44 days (range 10–56) only. The reason for premature discontinuation (50%) were either occurrence of early-onset (day 6) GVHD associated hyperbilirubinemia CTC grade 4 (n=1), transplantation-associated microangiopathy (TMA, n=3), sinusoidal obstructive syndrome (SOS) of the liver (n=6) or a drop of platelets after engraftment by at least 50% (n=2). Nine pts (37%) developed grade II–IV acute GVHD, however, chronic extensive GVHD was observed in 11 of 17 (64%) evaluable pts. TMA occurred in 7 pts (29%) with two cases of acute renal failure. In five out of seven patients with TMA either tacrolimus (n=4) or everolimus (n=1) blood through levels were slightly above the upper target level at the time of TMA appearance. The study was terminated prematurely because additional 6 pts (25%) developed SOS, which was fatal in two cases. With a median follow-up of 26 months, the 2-year overall survival rate is 47%. In conclusion, although this new combination appears to be effective as prophylactic regimen for acute GVHD, the incidence of TMA and SOS seems to be higher compared to other regimens. As a result this combination cannot be recommended as prophylactic regimen after busulfan-based intensive conditioning. However, studies in the context of TBI-based or reduced-intensity conditioning regimens might come to a different conclusion.

Severe Gut Acute Graft Versus host Disease (GVHD) Influence Thrombotic Microangiopathy in 86 Allogeneic Hematopoietic Stem Cell Recipients Who Received Tacrolimus-Based Regimen for GVHD Prophylaxis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1955-1955
Author(s):  
Jorge Labrador ◽  
Oriana López-Godino ◽  
Lucía López-Corral ◽  
Estefanía Pérez-López ◽  
Mónica Cabrero-Calvo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Thrombotic Microangiopathy ◽  
Acute Gvhd ◽  
Host Disease ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Acute Graft

Abstract Abstract 1955 Background and aims: Transplantation-associated thrombotic microangiopathy (TA-TMA) is a significant complication of allogeneic stem cell transplantation (HSCT). Although endothelial injury represents the final common pathway of disease, the exact pathophysiology of TA-TMA remains unclear. A variety of potential risk factors have been proposed such as different conditioning regimens, the development of acute graft versus host disease (GVHD), concomitant infection, or the use of calcineurin inhibitor (cyclosporine, tacrolimus) and sirolimus. The recent use of both tacrolimus and sirolimus for GVHD prophylaxis suggest increasing the risk of TA-TMA, especially in patients receiving busulfan and cyclophosphamide. However, there are little studies in which tacrolimus/sirolimus GVHD prophylaxis was compared with other tacrolimus-based regimens in order to determine the really increased incidence of TA-TMA. The purpose of this study was to determine the incidence and risk factors of TA-TMA in 86 allogeneic-HSCT recipients who received tacrolimus-based regimens (with sirolimus or with methotrexate) for GVHD prophylaxis. Patients and Methods: We conducted a retrospective cohort study of 86 consecutive allogeneic-HSCT recipients (aged over 18 years) transplanted in our unit between September 2007 and July 2012; GVHD prophylaxis consisted on tacrolimus and methotrexate (N = 19) or tacrolimus and sirolimus (N= 64); 3 patients received tacrolimus and sirolimus for acute GVHD treatment. Median age was 51 years (range 20–68) and 59.3% male. 40.7% of patients were diagnosed of acute leukemia, 23.3% myelodisplastic syndrome, 23.2% lymphoproliferative disorders, 7% multiple myeloma, 5.9% other hematological malignancies. The EBMT status at the moment of HSCT was intermediate/advanced in 63% of patients. The source of stem cells was peripheral blood in 87.2% and bone marrow in 12.8%. 57% of patients receiving an unrelated donor transplant. Nineteen patients (22.1%) received a HLA-mismatch graft. Reduced intensity conditioning was administered in 74.4%. 67.4% developed acute GVHD, 58.1% grade II-IV acute GVHD. Median follow-up was 248 days (range 16–1357). The diagnosis of TA-TMA was considered according to probable TMA criteria as defined by validation study by Cho et al. Results: TA-TMA occurred in 9/86 patients (10,5%): 2/19 patients in the tacrolimus-methotrexate regimen group (10.5%) and 7/67 in the tacrolimus/sirolimus regimen group (10.4%). Median time until diagnosis of TA-TMA was 67 days (range, 37 – 405 days), and 8/9 patients were diagnosed before the day +110 post-HSCT; none of them developed chronic GVHD previously to the diagnosed of TA-TMA. Several variables have been analyzed but only acute GVHD (p=0.026) and acute gut GVHD (p=0.007) were significantly associated with TA-TMA in the univariate analysis. Of note, in the tacrolimus/sirolimus group, only acute gut GVHD (p=0.04) but not acute GVHD, was associated with TA-TMA. In the multivariate analysis, only grade ≥2 acute gut GVHD retained their association with TA-TMA development (OR = 13.33, 95% CI = 1.51 – 117.38). Conclusions: In contrast to previously published evidence, these data support that the use of tacrolimus/sirolimus GVHD prophylaxis does not increase the risk of TA-TMA compared to tacrolimus/methotrexate regimen. However, none of the patients included in our study have received busulfan-cyclophosphamide conditioning. On the other hand, the most important risk factor for TA-TMA in allogeneic-HSCT recipients who received tacrolimus-based GVHD prophylaxis regimens was grade ≥2 acute gut GVHD. Consequently we propose especially close monitoring for TA-TMA in these patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

Human Cell ◽  
2019 ◽  
Vol 33 (1) ◽  
pp. 243-251 ◽  
Author(s):  
Laurence M. C. Kok ◽  
Laura Bungener ◽  
Geertruida H. de Bock ◽  
Anouschka Biswana ◽  
Geertiena van der Wal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Hla Antibodies ◽  
Host Disease ◽  
Graft Versus Host ◽  
Factors Associated

AbstractModerate to severe chronic graft-versus-host disease (cGVHD) is associated with high morbidity, hospital dependency and poor quality of life. In this study, we analyzed a well-defined consecutive series of 98 patients with acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) who received allogeneic stem cell transplantation with non-myeloablative (NMA) conditioning to determine risk factors associated with the severity of cGVHD. cGVHD was defined according to the 2005 National Institute of Health consensus criteria. Transfusions before transplantation, presence of HLA antibodies, composition of the graft (CD3+, CD19+, CD34+ cells), sibling or matched unrelated donor, female donor to male recipient, CMV serology and the development of acute GVHD (aGVHD), were considered potential risk factors. Multivariate Cox regression analysis identified the number of CD19+ 106/kg (HR 2.79; 95% CI 1.35–5.74), CD3+ 106/kg (HR 2.18; 95% CI 1.04–4.59) infused cells and the presence of patient HLA antibodies before transplantation (HR 2.34; CI 1.11–4.95) as significant risk factors for the development of moderate to severe cGVHD. In summary, we identified in a small, but well-defined cohort, 3 risk factors associated with the severity of cGVHD that should be validated in a larger multi-center study.

The Gut-Mucosa-Barrier-Function during Hematopoietic Stem-Cell Transplantation Predicts Acute Graft-Versus-Host Disease Severity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5075-5075
Author(s):  
Jan-Erik Johansson ◽  
Tor Ekman
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Barrier Function ◽  
Acute Gvhd ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Host Disease ◽  
Graft Versus Host

Abstract Background Graft-versus-host disease (GVHD) is the primary complication of allogeneic, haemopoietic, stem-cell transplantation (HSCT). From murine models, it has been revealed that gut toxicity increases the translocation of inflammatory mediators through the impaired intestinal barrier, which aggravates systemic GVHD. In patients, the intestinal barrier is disrupted after myeloablative conditioning but preserved after reduced intensity conditioning (RIC). The present study investigates, in a clinical situation, whether the severity of acute GVHD depends on intestinal-barrier function. Methods In 38 patients (21 myeloablative, 17 RIC), intestinal permeability was assessed before transplant and during the transplantation course (day −1 to +14). Blood levels of cytokines were assessed in parallel. Results Intestinal barrier integrity was preserved in RIC patients but disrupted in myeloablatively conditioned on day 4 (p = 0.0091) and on day 7 (p = 0.0014) compared with RIC patients. Patients with mild, acute GVHD (grades 0–1) had a significantly better preserved intestinal-barrier function (p = 0.042 on day 4) and lower TNF-a levels (p = 0.013 and 0.025 on day −1 and day +7 respectively), compared with patients with more pronounced GVHD (grades 2–4). Conclusion Intestinal barrier function predicts the severity of acute GVHD in patients and gives support to the assumption that gut protective strategies may diminish acute GVHD.

Hyperacute Graft-Versus-Host Disease: Analysis of Risk Factors, Clinical Manifestations and Outcomes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 734-734 ◽  
Author(s):  
Daniel R. Couriel ◽  
Rima Saliba ◽  
Marcos J. de Lima ◽  
Chitra Hosing ◽  
Borje Andersson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Clinical Manifestations ◽  
P Value ◽  
Skin Involvement ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Objective: To evaluate risk factors, clinical manifestations and outcome of hyperacute or early acute graft-versus host disease (GVHD), defined as that occurring within 14 days after hematopoietic stem cell (HSC) transplantation. Methods: A total of 815 consecutive patients transplanted at UT MD Anderson Cancer Center between 1/1998 and 9/2002 were retrospectively analyzed. Results: Of 381 patients presenting with acute GVHD, 22% (n=83) had biopsy-proven hyperacute GVHD. Grade I GVHD occurred in 12% of these patients, grade II in 53%, grade III in 13% and grade IV in 22%. The proportion of grade II-IV GVHD in this group was significantly higher (88%) than in the 298 patients presenting with acute GVHD between days 15 and 100 (64%, p value <0.001). The majority of patients with hyperacute GVHD had skin involvement (89%), followed by GI (43%), and liver GVHD (19%). Skin involvement was significantly more common (89% vs 76%, p value 0.01), and more severe (stage III or IV 63% vs 32%, p value <0.001) in the hyperacute group. There was no statistical difference in frequency and severity of visceral involvement. Risk factors for hyperacute GVHD were evaluated using Cox proportional hazards model. On univariate analysis, a mismatched (MM) related (HR=4.4, p value<0.001) matched unrelated (MUD) graft (HR=2.4, p value<0.001) and a myeloablative preparative regimen with or without TBI (HR=2.5, p value<0.001) were significantly associated with a higher rate of hyperacute GVHD. These effects remained significant in a multivariate model. Donor’s age greater than 40 years was associated with a lower rate of hyperacute GVHD (HR=0.6,p value=0.05), and there was a trend for increased rates for patients receiving sex mismatched grafts, solid tumor transplants or multiple (>5) chemotherapy regimens before transplant. Age, disease status, GVHD prophylaxis, or stem cell source (BM vs peripheral HSC) were not associated with hyperacute GVHD. Overall mortality was significantly higher within 6 months post transplant for patients with hyperacute GVHD (HR=2.2, p value <0.001) compared to all other patients, or to patients developing acute GVHD after day 14 (HR=1.6, p = 0.009). GVHD-related death was also significantly higher (HR=2.3, p=0.007) in the hyperacute GVHD group. Conclusions: Hyperacute GVHD occurs in a substantial proportion of patients undersgoing HSC transplant, even prior to neutrophil engraftment. Skin involvement, grades 3–4 GVHD and a higher mortality are common features of this syndrome . Patients at high risk or with a diagnosis of hyperacute GVHD should be included in clinical studies whenever possible.

Identification Of Patients At High Risk Of Chronic Graft-Versus-Host Disease: Gvhd Prophylaxis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4611-4611
Author(s):  
Gabriel Afram ◽  
Jose Antonio Pérez Simón ◽  
Mats Remberger ◽  
Teresa Caballero-Velázquez ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Host Disease ◽  
Graft Versus Host ◽  
Female Donor ◽  
Reduced Intensity

Introduction Chronic Graft-versus-Host disease (cGVHD) remains a major cause of morbidity and mortality in long-term survivors after allogeneic hematopoietic stem cell transplantation (ASCT). Among the major risk factors previously noted is sex-mismatch, acute GVHD and peripheral hematopoietic blood stem cell grafts (PBSC). Our aim in this study was to determine risk factors for cGVHD and evaluate the impact of ATG on cGVHD in a multi-centre setting. Methods Patients from three centers (Stockholm, Sant Pau, Barcelona and Salamanca) were included. Retrospective data analysis was conducted for all patients (n=820) transplanted between 2000 and 2006. In our cohort 91% had malignant disease, 57% received HLA-identical sibling donor grafts, 13% received grafts with one HLA-A, -B or –DR antigen mismatch and 30% received grafts from HLA-A, -B and –DR matched unrelated donors. Reduced intensity conditioning was given to 65% of the patients. Chronic GVHD was classified according the National Institute of Health consensus criteria. Results Overall incidence of cGVHD was 46% for patients surviving more than three months after ASCT (n=747). Older patient age HR 1.15 (95% CI 1.07-1.24), p<0.001, acute GVHD HR 1.30 (95% CI: 1.04-1.63), p=0.024, and reduced intensity conditioning (RIC) HR 1.36 (95% CI 1.04-1.79) p=0.028 were shown to significantly increase the risk of overall cGVHD in multivariate analysis. In addition, female donor to male recipient HR 1.43 (95% CI 1.07-1.92), p=0.02, RIC HR 1.65 (95% CI 1.18-2.30) p=0.003, and PBSC HR 1.90 (95% CI 1.14-3.16), p=0.01 significantly influenced the risk of moderate-to-severe cGVHD in multivariate analysis. For both overall and moderate-to-severe cGVHD, ATG had a protective effect with HR 0.41 (95% CI 0.32-0.52) p<0.001 and HR 0.32 (95% CI 0.23-0.46) p<0.00, respectively. Accordingly, we developed a scoring system including all variables influencing the risk of cGVHD in multivariate analysis allowing us to distinguish patient cohorts with 12% to 71% incidence of cGVHD (figure 1). Relapse free survival (RFS) was significantly impaired in the group with severe cGVHD. RFS was not affected significantly by the addition of ATG. All three centers had similar overall survival for patients with cGVHD. Conclusion RIC increases the risk for both overall and moderate to severe cGVHD. Acute GVHD and older recipient age are significant risk-factors for overall cGVHD and female donor to male recipient and PBSC for moderate to severe cGVHD. ATG significantly reduces the risk of all grades of cGVHD without having a negative outcome on RFS. Therefore, in order to prevent overall and moderate-extensive cGVHD it should be added to the RIC regimen in older patients and in male patients with female donors after PBSC grafts. Disclosures: Ringden: Gilead : Invited to Gilead on July 28, 2011, to participate in an Advisory Board Meeting on Treatment of invasive fungal infection. Other. San Miguel:Jansen, Celgene, Onyx, Novartis, Millenium: Consultancy, Membership on an entity’s Board of Directors or advisory committees.

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