Withdrawal Of Immunosuppressive Treatment Research Articles

WED-315 - Celiac disease in patients with autoimmune hepatitis is associated with a milder liver disease course and a better chance of immunosuppressive treatment withdrawal

WED-315 - Celiac disease in patients with autoimmune hepatitis is associated with a milder liver disease course and a better chance of immunosuppressive treatment withdrawal

People with autoimmune hepatitis and celiac disease have a milder liver disease course and a better chance of immunosuppressive treatment withdrawal.

People with autoimmune hepatitis and celiac disease have a milder liver disease course and a better chance of immunosuppressive treatment withdrawal.

Temporary withdrawal of immunosuppressive treatments in patients with hidradenitis suppurativa during COVID-19 pandemic: A retrospective cross-sectional study

Aims: There is currently no evidence-based guideline to show how to manage immunosuppressive treatment in patients with hidradenitis suppurativa (HS) during the Coronavirus disease-2019 (COVID-19) pandemic. Therefore, we updated our routine clinical protocol to 1) inform patients with ongoing treatment about the potential risks of their medications in the case of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, 2) discuss opt out of treatment temporarily, and 3) perform a closer follow-up on a monthly basis. The aim of this study was to evaluate the clinical outcomes in patients with HS, who suspended and continued immunosuppressive therapy following COVID-19 outbreak. Methods: This retrospective study included patients with HS, who had been receiving biologic/immunosuppressive treatment when the COVID-19 pandemic was announced. Those who withdrew treatment for any reason or continued were analyzed. The primary endpoint was physician-diagnosed disease exacerbation. The secondary outcomes were changes in visual analogue scale (VAS) and COVID-19 diagnosis. Results: A total of 37 patients were included in the analysis. The majority of the patients were on adalimumab treatment (n=33). Fifteen (40.5%) patients withdrew the treatment for COVID-19 related concerns. During 83.2±0.6 days of follow-up following the withdrawal, all patients in this group had at least one exacerbation. Also, the mean VAS score increased from 5.7±0.56 to 8.6±0.57 (p=0.001). On the other hand, three patients (13.6%) who continued the treatment reported worsening in disease course, 12 patients (54.5%) remained stable and seven of them (31.9%) had clinical relief. We did not observe any confirmed SARS-CoV-2 infection in any of our 37 HS patients. Conclusions: The present study suggests that even a temporary withdrawal of biologic/immunosuppressive treatments may have significant adverse consequences on disease course and quality of life in patients with HS. These individuals may safely continue the treatment provided that maximum measures are taken to avoid COVID-19 infection.

Dissociation of humoral and cellular immune responses in kidney transplant recipients with EBV mucocutaneous ulcer

EBV-positive mucocutaneous ulcer (EBV-MCU) is a rare EBV-positive B-cell lymphoproliferative disorder occurring in immunocompromised patients such as patients with solid organ or hematopoietic stem cells transplantation. EBV-MCU often consists of an isolated and circumscribed cutaneous or mucosal ulcerative lesion with a self-limited growth potential and a high regression rate upon immunosuppressive treatment withdrawal or rituximab therapy. Nevertheless, the pathophysiology of this latent infection leading to clonal lymphoproliferation is not well established. We report here two cases of EBV-MCU in kidney transplant recipients with a dissociated immune response to EBV with the absence of EBV-related antibodies and a positive T-cell response to EBV suggesting a potential specific oncogenic mechanism in this lymphoproliferative disorder.

Chimerism and tolerance: past, present and future strategies to prolong renal allograft survival.

Immunological factors are a major cause of kidney allograft loss. Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival; however, they in turn contribute to long-term kidney allograft loss from chronic CNI nephrotoxicity. Tolerance induction in transplantation can avoid the long-term adverse effects of immunosuppressive medications. This review aims to critically discuss recent efforts in inducing transplantation tolerance. Tolerance induction mediated by chimerism has shown some promise in minimizing or even complete withdrawal of immunosuppressive treatments in kidney allograft recipients. There has been a number of approaches as varied as the number of centres conducting these trials. However, they can be grouped into those mediated by transient microchimerism and those facilitated by more stable macro or full donor chimerism. The success rates in terms of long-term drug-free graft survival has been limited in microchimerism-mediated tolerance induction approaches. Mixed macrochimerism of less than 50% donor may be unstable with mostly the recipient's native immune system overpowering the donor chimeric status.Tolerance induction leading to chimerism has been limited to living donor kidney transplantation and additional long-term outcomes are required. Furthermore, immune monitoring after tolerance induction has faced a limitation in studying due to a lack of sufficient study participants and appropriate study controls. Tolerance induction is one of several strategies used to prolong kidney allograft survival, but it has not been routinely utilized in clinical practice. However, future applications from the trials to clinical practice remain limited to living donor kidney transplantation. Once further data regarding tolerance inductions exist and practicality becomes widely accepted, tolerance induction may shift the paradigm in the field of kidney transplantation to achieve the best possible outcome of 'One Organ for Life'.

Sustained Remission After Treatment Withdrawal in Autoimmune Hepatitis: A Multicenter Retrospective Study.

In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases < 0.6 × ULN (OR = 7.1; CI: 1.3; 36.7). Thirty-nine patients stopped therapy after a median biochemical response of 48.6months. Twenty-four of them had a biopsy before treatment withdrawal: 21 were histological responders. The cumulative rate of relapse was 25% at 64months. This study indicates that older age, mild-to-moderate fibrosis at diagnosis and serum aspartate aminotransferases in the lower range of normal are independent predictors of histological response in AIH with prolonged biochemical response. The relapse rate after treatment withdrawal may be limited to 25% at 64months when patients are selected on the basis of prolonged biochemical remission and, when available, histological response.

P763 Epstein–Barr virus serological status in paediatric patients with inflammatory bowel disease

Abstract Background The impact of Epstein–Barr virus (EBV) infection on the clinical outcomes of children and adolescents with inflammatory bowel disease (IBD) is not well known. The aim of the study is to evaluate the seroprevalence, seroconversion rate and complications associated with EBV infection in a cohort of paediatric IBD (PIBD) patients at a tertiary care hospital. Methods A descriptive study was performed collecting demographic, clinical and treatment data from medical records as well as EBV serological status of paediatric IBD patients from 2012 to 2018. In seronegative patients, seroconversion rate was evaluated. Complications associated with primary EBV infection were described. Since September 2016, EBV serology was included into the initial work-up for PIBD patients. For those patients who did not have EBV study at IBD onset, it was performed during follow-up. Results A total of 307 patients with PIBD were diagnosed between 2012 and 2018. EBV status was available for 131 patients (43%). Of those, 57% had Crohn’s Disease, 41% Ulcerative Colitis, and 2% IBD unclassified (66% males; median age at IBD diagnosis: 13.2 years (IQR: 0.8–17.8)). In 102 patients serological EBV status was determined at IBD onset; while in 17 patients it was performed during the follow-up. Overall, EBV seroprevalence was 67%, and no differences were observed regarding age (over or under 10 years-old). EBV seroprevalence was higher in females than in males (80% vs. 60.5%, p = 0.02). Regarding IBD treatment, 84% had received immunosuppressive treatment [thiopurines (32%), anti-TNF (9%) and combined treatment (59%)], without differences in the seroprevalence rate according to the treatment modality. Forty-three patients were seronegative, and 12 of them had a second determination during follow-up. Overall, 5 patients showed seroconversion (42%) after a mean follow-up of 24 months (IQR: 22–26). All these patients had received treatment with thiopurines: 2 patients presented symptomatic mononucleosis with neutropenia, requiring hospital admission and withdrawal of immunosuppressive treatment and 3 patients had asymptomatic primary infection. Conclusion EBV seroprevalence in our paediatric IBD cohort is similar as previously described in the literature. EBV status study in patients with IBD, especially prior to initiation of thiopurines, may be useful to plan subsequent follow-up since a non-negligible percentage of them could present with complicactions of primary EBV infection under immunosuppressive treatment.

Permanent immunosuppression in SLA/LP-positive autoimmune hepatitis is required although overall response and survival are similar.

Antibodies against soluble liver antigen/liver pancreas (anti-SLA/LP) are highly specific for autoimmune hepatitis (AIH) and have been linked with a more severe clinical course of the disease, frequent relapses after treatment withdrawal and worse outcome. To address definitely the clinical significance of anti-SLA/LP, we investigated a large number of anti-SLA/LP-positive and -negative patients followed in three referral centres. Prospectively collected data from 89 anti-SLA/LP-positive AIH patients (29 from Hamburg-Germany, 20 from Bologna-Italy and 40 from Larissa-Greece) were analysed retrospectively. Age- and sex-matched anti-SLA/LP-negative patients served as disease controls (n=230; 1:2.5 ratio). In respect to baseline characteristics, anti-SLA/LP-positive patients were more frequently asymptomatic compared to anti-SLA/LP-negative (P<.05). However, anti-SLA/LP-positive patients did not differ from anti-SLA/LP-negative in terms of the overall response to treatment, disease progression and survival even though, they were less likely to achieve corticosteroid withdrawal (P<.05), needed longer treatment duration to achieve first complete response (P<.001) and relapsed more frequently after treatment withdrawal compared to anti-SLA/LP-negative patients (P=<.001). We showed that anti-SLA/LP antibodies do not characterize a group of AIH patients with distinct features and cannot identify patients with a more severe form of the disease or worse survival. Most importantly, however, anti-SLA/LP-positive patients appear to require lifelong immunosuppression as they are less likely to achieve the cessation of corticosteroids and present higher relapse rates after treatment withdrawal. Therefore, close long-term monitoring should be advised in all anti-SLA/LP-positive patients after withdrawal of immunosuppressive treatment.

Stopping immunosuppressive treatment in autoimmune hepatitis (AIH): Is it justified (and in whom and when)?

Initial treatment of autoimmune hepatitis (AIH) with prednisolone±azathioprine is based on randomised controlled trials. Many patients receive long-term immunosuppressive treatment to prevent disease relapse; this strategy has a weaker evidence base. To consider whether immunosuppressive treatment (IST) withdrawal in AIH is justified and to develop a rationale for patient selection. We reviewed published papers between 1972 and 2018, which addressed the outcomes of IST withdrawal and/or complications of IST in AIH. (1) AIH relapse rates after withdrawal of IST vary between 25% and 100%. There is heterogeneity in these studies regarding relapse definition, IST duration prior to withdrawal and criteria for biochemical and histological remission prior to withdrawal. (2) Factors associated with relapse following IST withdrawal include: (a) absence of an identifiable initial disease trigger, (b) presence of other autoimmune diseases, (c) longer time to biochemical remission and (d) elevated serum transaminases on treatment withdrawal. Reports of associations between relapse and age, IST duration and failure of histological remission have been inconsistent. (3) Continued IST reduces risk of AIH relapse over at least 5years. However, there is no evidence that routine (as opposed to selective) long-term IST improves disease outcome. (4) Patients with AIH have an increased risk of extrahepatic cancer, notably non-melanoma skin cancer, to which long-term IST may contribute. Long-term corticosteroid therapy is associated with weight gain, low-trauma fractures, diabetes and possibly vascular disease. While further studies are needed, evidence supports a strategy of IST withdrawal in some patients with AIH who have achieved remission.

Atrium Advanta V12 Large Diameter Stent-Graft Applications for Infrarenal Abdominal Aortic Pseudoaneurysms (due to Behcet Disease): Safety and Efficacy

The aim of the study was to determine the safety and effectiveness of Atrium Advanta V12 large diameter stent-graft applications for infrarenal abdominal aortic pseudoaneurysms (due to Behcet disease [BD]). Data of Advanta V12™ (Atrium Europe B.V, Mijdrecht, the Netherlands) applied 12 female patients (mean age 30.5±6.3, range 26-44) with infrarenal abdominal aortic pseudoaneurysms were analyzed retrospectively. All Advanta V12 large diameter stent grafts were implemented from right or left sided 12F femoral sheaths. Stent grafts with 12-16mm in size and 29-61mm in length were utilized. Technical success rate, procedure-related mortality and morbidity, and primary patency rate at 4 years were evaluated. Technical success rate was 100%. Neither procedure-related mortality nor morbidity was determined. The mean aortic diameter was 14.0±0.8mm for pseudoaneurysmatic abdominal aortas. The mean follow-up period was 46.5±40.3months (range 18-75). During follow-ups, only one recurrent aneurysm has evolved at the stenting site due to patients' withdrawal of immunosuppressive treatment. The advent of a new aneurysm proximal or distal to the stent-graft region or at the femoral access localization was not observed. There were no stent occlusions. Primary patency rate at 4 years was 100%. Complete aneurysm exclusion was achieved 100% at 48months. The use of Advanta V12 large diameter stent grafts for infrarenal abdominal aortic pseudoaneurysms (due to BD), especially in female patients with small aortic diameter, is safe and efficient. Primary patency rate of the stent grafts at 4 years is excellent.

EBV-induced lymphoproliferative disorders in rheumatic patients: A systematic review of the literature

ObjectivesEpstein-Barr virus (EBV) is involved in the pathogenesis of approximately 40% of lymphoproliferative disorders (LPDs) arising in patients receiving immunosuppressive treatment (IST) for rheumatic diseases, but data from large cohorts are still not available. We aimed to identify clinicopathological features, management and outcome of this condition. MethodsWe reviewed all published cases of EBV-encoded RNA (EBER)-positive LPDs and included in our analysis one unpublished patient diagnosed in our Hospital. We excluded those cases without an underling rheumatic condition, a specific IST or not reporting univocal data. ResultsIn the cumulative cohort of 159 patients, most were affected by rheumatoid arthritis (83.0%) and treated with methotrexate (75.4%). 68.5% of LPDs developed between the age of 40 and 70 years, after 13.3±9.6 years from rheumatic disease onset and 58.7±47.0 months of IST. LPDs were mostly B-cell lineage derived (39.0%), Ann Arbor disease's stage I (38.3%) and presented with extra-nodal involvement in 63.1%, which was most frequently represented by central nervous system (17.6%). The most common approach was IST withdrawal (93.3%), variably associated with radiotherapy(RT)/chemotherapy(CT) in 38.3% of cases. Overall, 61.7% of patients achieved a complete remission (CR; 30.2±24.0 months). Among published cases of patients that only suspended IS as first line treatment approach, 67.2% achieved CR. No significant demographic, clinical and histological differences between patients who achieved CR and who did not, and between who achieved CR by IST withdrawal alone and who did not were observed (P>0.05 in all comparison). ConclusionsThe current study reviews all the published evidences of EBV-induced LPDs in patients receiving IST treatment for rheumatic conditions.

Feline non-regenerative immune-mediated anaemia: features and outcome in 15 cases.

Pure red cell aplasia (PRCA) and non-regenerative immune-mediated haemolytic anaemia (NRIMHA) are uncommon causes of non-regenerative anaemia affecting the bone marrow in the cat. This retrospective study aimed to describe the clinical features, treatment and outcome (remission and survival) of cats with these disorders. Cases of PRCA and NRIMHA presenting between 2009 and 2013 were retrieved. Clinical features including signalment, history, clinical signs and diagnostic investigations were recorded, as well as treatment(s) used and outcome (remission and survival). Outcome was compared for PRCA and NRIMHA. Fifteen cats met inclusion criteria: seven with PRCA and eight with NRIMHA. The majority (12/15) were younger than 3 years of age. Volume overload was common (8/11). Treatment with whole blood transfusions with or without Oxyglobin was necessary in most cats (14/15) and resulted in congestive heart failure in one cat. Most cats (11/15) achieved remission 12-42 days after starting immunosuppressive treatment. Treatment protocols associated with remission were glucocorticoids alone (remission in 6/7 cats), glucocorticoids and chlorambucil (remission in 3/6 treated cats), glucocorticoids and ciclosporin (one cat only) and ciclosporin alone (one cat only). Relapse was observed in 3/11 cats, and 8/11 cats were still receiving treatment at the time of follow-up. Outcome (remission and survival) did not differ between PRCA and NRIMHA. PRCA and NRIMHA are uncommon causes of anaemia in predominantly young cats. The prognosis is reasonable, with a mortality rate of 27%, and it can take at least 6 weeks before remission is observed. Following clinical remission, gradual withdrawal of immunosuppressive treatments should be attempted, with close monitoring for relapse; some cats may require long-term treatment. This study is the first to report the use of chlorambucil as an adjunctive immunosuppressant in these cases. Outcome did not differ for PRCA and NRIMHA.

Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host disease

AbstractSclerotic chronic graft-versus-host disease (GVHD) can result in disability after allogeneic hematopoietic cell transplantation. We assessed the incidence and risk factors of sclerosis and its association with transplant outcomes among 977 consecutive patients treated with systemic immunosuppression for chronic GVHD. Sclerosis was defined when cutaneous sclerosis, fasciitis, or joint contracture was first documented in the medical record. Seventy (7%) patients presented with sclerosis at the time of initial systemic treatment for chronic GVHD, and the cumulative incidence of sclerosis increased to 20% at 3 years. Factors associated with an increased risk of sclerosis included the use of a mobilized blood cell graft and a conditioning regimen with >450 cGy total body irradiation. Factors associated with a decreased risk of sclerosis included the use of an HLA-mismatched donor and a major ABO-mismatched donor. Development of sclerosis was associated with longer time to withdrawal of immunosuppressive treatment but not with risks of overall mortality, nonrelapse mortality, or recurrent malignancy. We found a substantial incidence of sclerosis in patients with chronic GVHD. Development of sclerosis can cause disability but does not affect mortality or recurrent malignancy in patients with chronic GVHD.

Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease

AbstractThis study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD.

Response to Immunosuppressive Treatment Predicts Outcome in Patients with Chronic Graft-versus-Host Disease: A Single-Center Analysis of Longitudinal Data

It has been reported that chronic graft-versus-host disease (cGVHD) is associated with significant morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). The risk of relapse is generally reduced when cGVHD is present, but prognosis may be affected by increased toxicity and/or risk of infection associated with immunosuppressive treatment (IST). We performed a longitudinal data analysis of cGVHD, including the evolution of cGVHD itself over time in response to IST, in a single-center cohort of 313 consecutive patients undergoing allo-SCT. We found that lack of sustained response without withdrawal of IST within 6 months of cGVHD development was associated with higher transplantation-related mortality (hazard ratio, 2.32; 95% confidence interval, 1.24-4.33) compared with cGVHD-free patients. Conversely, response conferred better overall survival (hazard ratio, 0.42; 95% confidence interval, 0.18-0.95). Our analytical approach allowed us to integrate the evolution of cGVHD in a predictive model of transplantation outcome; notably, remission associated with permanent discontinuation of IST within the first 6 months from the occurrence of cGVHD seemed to correlate most closely with final outcome. Further confirmation from larger studies is needed.

Cryptosporidiosis in Children With Acute Lymphoblastic Leukemia on Maintenance Chemotherapy

Cryptosporidium is recognized as a cause of diarrhea associated with a high mortality in immunocompromised patients. We report on 2 pediatric cases of cryptosporidiosis during maintenance chemotherapy of acute lymphoblastic leukemia. The patients presented severe diarrheas, 1 of them was complicated by a cholangitis. Withdrawal of immunosuppressive treatments and adjunction of an adequate antiparasitic treatment cured the Cryptosporidium infection in both cases.

Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

AbstractThis study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after high-intensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points.

Association of Graft-Versus-Host Disease and Immunosuppressive Treatment with Risks of Recurrent Malignancy and Mortality After Allogeneic Hematopoietic Cell Transplantation

AbstractAbstract 218 Background:Graft-versus-leukemia (GVL) effects are closely associated with graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). In a reexamination of GVL effects, we evaluated acute and chronic GVHD defined by NIH consensus criteria and immunosuppressive treatment (IST) as risk factors for recurrent malignancy after HCT. Patients and methods:We analyzed a cohort of 2656 consecutive patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) who received allogeneic HCT after high-intensity conditioning between 1992 and 2005. The onset of NIH chronic GVHD was ascertained by retrospective chart review using follow-up information obtained by our Long Term Follow Up clinic. Rates and hazards of recurrent malignancy and mortality were analyzed according to GVHD and IST as time-varying covariates. To illustrate the effect of time-varying covariates, we calculated the rate of recurrent malignancy per patient-year according to prior GVHD within sequential 90-day intervals after HCT. Cox proportional hazard models were adjusted for potential factors affecting outcomes. Results:The median patient age at HCT was 39 years (range, 0 to 71 years). Donors were HLA-identical relatives (n=1088), HLA-matched unrelated volunteers (n=912), HLA-mismatched relatives (n=243), and HLA-mismatched unrelated volunteers (n=413). GVHD prophylaxis was mostly cyclosporine and methotrexate (n=1885, 71%). Relapse rates per patient-year declined from 3 months until at least 36 months after HCT for patients with prior acute GVHD or NIH chronic GVHD (Figure). Patients without prior GVHD showed a much less pronounced decline between 12 and 30 months after HCT. Adjusted Cox analysis showed that acute GVHD and NIH chronic GVHD were associated with statistically similar reductions in risk of late recurrent malignancy beyond 18 months after HCT, with no incremental effect of chronic GVHD in patients with prior acute GVHD (Table 1). GVL effects were demonstrable in patients with CML or AML but not in those with ALL or MDS/MPN. Discontinuation of IST was associated with a decreased risk of recurrent malignancy among patients without prior GVHD but not among those with prior GVHD (Table 2). Grades III–IV acute GVHD and NIH chronic GVHD with prior acute GVHD were associated with a statistically significant increase in risk of early mortality between 3 and 18 months, but grade II acute GVHD and NIH chronic GVHD without prior acute GVHD were not. [Display omitted] Conclusion:Both acute and NIH chronic GVHD are associated with potent GVL effects, but NIH chronic GVHD does not confer any incremental benefit after acute GVHD. Withdrawal of IST was associated with a reduction in risk of recurrent malignancy in patients without prior GVHD. Analyses of GVL effects should account for time from HCT, the history of GVHD, type of malignancy and IST. Immune manipulations such as prophylactic donor lymphocyte infusion or early withdrawal of IST may represent reasonable approaches to decrease the risk of recurrent malignancy in patients without prior GVHD, if the risk of GVHD could be minimized. Disclosures:No relevant conflicts of interest to declare.

Review article: influenza A (H1N1) virus in patients with inflammatory bowel disease

Infection with influenza A (H1N1)v (swine flu) has caused widespread anxiety, among patients who are potentially immunocompromised, such as those being treated for inflammatory bowel disease. To provide guidance for physicians and their patients on the risk, prevention and management of influenza A (H1N1)v infection. Medline was searched using the following key words: 'swine flu', 'immunosuppression', inflammatory bowel disease', 'recommendations', 'immunization', 'vaccination'. Organizations such as European Centre for Disease Prevention and Control, the Centers for Disease Control and Prevention and the World Health Organization were consulted for recent papers and recommendations regarding immunocompromised patients and influenza A (H1N1)v infection. Pandemic influenza A (H1N1) virus predominantly affects young patients. Those who are immunocompromised because of underlying disease or treatment are considered at higher risk of complications from influenza A (H1N1). They should be offered prevention (vaccination, postexposure prophylaxis) or treatment with antiviral drugs, if affected. Pneumococcal infection is a complication of influenza infection; therefore, pneumococcal vaccination appears advisable. Seasonal influenza vaccination is also recommended. Withdrawal of immunosuppressive treatment appears advisable during severe active infection if possible. Pragmatic advice is the best that can be offered in the current circumstances because of paucity of evidence. Investigation into the impact of influenza A (H1N1)v infection in young people with chronic conditions is needed.

Is the Intracellular ATP Concentration of CD4+ T-Cells a Predictive Biomarker of Immune Status in Stable Transplant Recipients?

Intracellular ATP (iATP) production in CD4(+)-T cells has been proposed as a biomarker for routine personalized monitoring in transplant recipients. The aim of our study was to measure this biomarker in adult renal and liver transplant recipients receiving moderate immunosuppressive treatment (IST) during the maintenance period and to evaluate whether this biomarker can effectively predict clinical status (stability, rejection, or infection) and drug effect. iATP concentration and trough blood levels of IST were evaluated in 84 adult transplant recipients (50 renal and 34 liver) during the maintenance period. One hundred and fifty healthy donors were also recruited as a control group. In addition, 22 of 34 liver transplant recipients were included in a clinical study in which IST was withdrawn gradually until total elimination. Most of the patients evaluated had iATP levels in the moderate immune response zone during a posttransplantation maintenance period with no relevant clinical events. iATP levels were significantly lower in transplant patients with infection (n=3) than in those free of infection. In the IST withdrawal study, 10 of 22 liver transplant recipients have achieved complete withdrawal and 12 receive 50% of IST. So far, there have been eight rejections once IST began to be withdrawn. None of these patients had iATP in the strong immune response zone (risk of rejection). iATP seems to be more effective in identifying overimmunosuppressed patients with a high risk of adverse events (IST-safety) than in identifying those with a high risk of rejection (IST-efficacy) and should be used in combination with other biomarkers of immunosuppressive effect to improve the efficacy of IST.