Incidence Of CMV Reactivation Research Articles

Cytomegalovirus reactivation in immunocompetent mechanical ventilation patients: a prospective observational study

BackgroundCytomegalovirus (CMV) reactivation is associated with adverse prognoses of critically ill patients. However, the epidemiology and predictors of CMV reactivation in immunocompetent patients receiving mechanical ventilation (MV) are not clear. The aim of this study was to investigate the epidemiology and predictors of CMV reactivation in immunocompetent patients requiring MV.MethodsA single-center, prospective observational study (conducted from June 30, 2017 to July 01, 2018) with a follow-up of 90 days (September 29, 2018) that included 71 CMV-seropositive immunocompetent patients with MV at a 37-bed university hospital general intensive care unit (ICU) in China. Routine detection of CMV DNAemia was performed once a week for 28 days (Days 1, 7, 14, 21, and 28). CMV serology, laboratory findings, and clinical data were obtained during hospitalization.ResultsAmong 71 patients, 13 (18.3%) showed CMV reactivation within 28 days in the ICU. The median time to reactivation was 7 days. CMV reactivation was related to various factors, including body mass index (BMI), sepsis, N-terminal pro-b-type natriuretic peptide (NT-proBNP), blood urea nitrogen (BUN), and hemoglobin (Hb) levels (P < 0.05). In the multivariate regression model, BMI, Hb level, and sepsis were independently associated with CMV reactivation patients (P < 0.05). Moreover, the area under the receiver operating characteristic (AUROC) of BMI, Hb, and BMI combined with Hb was 0.69, 0.70, and 0.76, respectively. The duration of MV, hospitalization expense, length of ICU stay, and 90 day all-cause mortality rate in patients with CMV reactivation was significantly higher than in those without CMV reactivation (P < 0.05).ConclusionsAmong immunocompetent patients with MV, the incidence of CMV reactivation was 18.3%. CMV reactivation was associated with several adverse prognoses. BMI, Hb, and sepsis were independent risk factors for CMV reactivation. BMI and Hb may predict CMV reactivation.

The Presence of Recipient CMV Immunodominant Human Leukocyte Antigen (HLA) Alleles Affect Outcomes after Haploidentical (HI) Hematopoietic Stem Cell Transplantation (HSCT)

CMV reactivation is associated with increased treatment-related mortality (TRM), decreased overall survival (OS), and in some analyses, protection from relapse after HSCT. We previously showed that CMV reactivation was significantly higher in HI versus matched related HSCT recipients receiving an identical preparatory regimen, implicating HLA mismatch as a contributor to reactivation. It is known that specific CMV immunodominant HLA alleles (CMV ID alleles) are associated with more efficient antigen presentation and protection from CMV. We hypothesized that a match at a CMV ID allele in the shared haplotype of the donor and recipient pairs may overcome the disadvantage proffered by HI HSCT with respect to CMV. As a control, we tested whether the presence of a CMV ID allele in either the donor or recipient, as opposed to a match at the CMV ID allele, was the more important impactor of outcomes. This information would potentially impact donor selection and identify HI recipients with greater risk for CMV-related complications.MethodsThis is a retrospective, analysis of 138 HI HSCT recipients at risk for CMV reactivation as defined by the presence of positive CMV serologic status in the recipient, donor, or both. All recipients were treated on the Jefferson 2 step approach in which after conditioning, a fixed T cell dose (2 x 108/kg) is administered (step 1), followed 2-3 days later by cyclophosphamide (CY) for bidirectional tolerization. Two days after CY, patients receive a CD34-selected donor product (step 2). To be included in the analysis, patients had to successfully engraft and be alive for at least 1 month post HSCT. Outcomes related to CMV, 1) reactivation incidence, 2) peak copy number of initial CMV reactivation occurring by d+100, 3) TRM, 4) relapse related mortality (RRM), and 5) OS, were tested in 3 contexts: the presence vs the absence of a CMV ID allele in the recipient or the donor, or the presence or absence of a donor/recipient (R/D) match at the same CMV ID allele. CMV ID alleles were defined as HLA A01:01, A02:01, A24:02, B07:02, B08:01, B35:01 and C07:02. Statistics used: incidence of CMV reactivation=Chi-Square; comparison of peak CMV copy numbers=T-test; assessment of RRM and NRM=cumulative incidence (CI); OS=Kaplan-Meier method.Results:A CMV ID allele was present in 68.1% recipients and 66.7% donors. 41.7% of D/R pairs were matched at the same CMV ID allele. The incidence of CMV reactivation was not associated with a D/R CMV ID allele match or recipient or donor CMV ID allele positivity. Peak CMV levels were lower in the presence of any recipient or donor CMV ID allele, but only approached significance in D/R pairs matched at the same CMV ID allele (p=0.065) with a mean of 8.7 x 10e3 vs 4.1 x10e4 copies/ml by PCR in matched vs non-matched pairs respectively. At 3 years, in recipients who matched their donor at 1 or more CMV ID alleles vs those who had no match, CI of NRM was 28% vs 26% (p=0.48) and 16% vs 32% (p=0.07) for RRM. In recipients with vs without a CMV ID allele CI of NRM was 23% vs 36% (p=0.059) and 20% vs 36% for RRM (p= 0.02) (Figure). In recipients with donors who possessed a CMV ID allele vs not, CI of NRM was 27% vs 28% (p=0.80) and 21% vs 31% for RRM (p= 0.12). OS in recipients who were matched at the same CMV ID allele with their donors or who possessed a CMV ID allele was 51% vs 37% (p=0.062) and 52% vs 27% (p=0.001) respectively as compared to recipients negative for these alleles.Conclusion:This analysis suggests that matching HI D/R pairs at a CMV ID epitope may reduce CMV peak copy number but has no significant effect on post HSCT reactivation. Recipient positivity for a CMV ID allele was strongly associated with improvement in NRM, RRM, and OS. Whether the benefit is specific to improved CMV control or to a more efficient antigen presentation in general by these alleles is unknown, but should be further investigated. This data requires confirmation with multivariate analysis. [Display omitted] DisclosuresWagner:Novartis: Research Funding.

A195 A RARE CAUSE OF SEVERE REFRACTORY DIARRHEA IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY ASSOCIATED INTESTINAL ENTEROPATHY

Abstract Background CVID is the most common type of severe antibody deficiency. Gastrointestinal manifestations affect approximately 20–50% of patients. Boland et al. described in a case series that 2/3 CVID patients were able to achieve clinical and endoscopic remission with Vedolizumab. This α4β7 integrin antagonist inhibits intestinal T cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. However, despite its novel use for this indication, limited data is available on the consequences of this therapy in patients with CVID. Aims To report on a case assessing the efficacy and outcomes of Vedolizumab for the treatment of CVID associated autoimmune enteropathy. Methods We present the case of a 50-year-old male presenting with severe refractory diarrhea and malnutrition. A colonoscopy demonstrated patchy ulceration and biopsies revealed ulcerated active colitis, negative for CMV. He was treated with Vedolizumab and Total Parental Nutrition (TPN). His diarrhea resolved, he gained 20 kg and he was weaned off TPN. In 2019, he re-presented with severe diarrhea. Subsequently endoscopic evaluation revealed patchy edematous colonic mucosa and biopsies demonstrated minimally active colitis, negative for CMV. He again responded to Vedolizumab re-induction, however shortly after, his diarrhea returned aggressively. CT enterography demonstrated active jejunal inflammation. Subsequently, an EGD revealed multiple duodenal ulcers and luminal narrowing. Biopsies of the small bowel were sent to histopathology. Results CMV superinfection was diagnosed on pathology (image 1). This patient’s diarrhea completely resolved with IV Gancyclovir and he was discharged on maintenance treatment with oral Valganciclovir. Conclusions This represents the first reported case of CMV enteritis secondary to Vedolizumab for the treatment of CVID associated autoimmune enteropathy. In this case, clinical and endoscopic remission was observed with Vedolizumab, however subsequently hampered by CMV reactivation. Hommel et al., published a positive correlation in a single centre retrospective cohort study of CMV reactivation in patients with ulcerative colitis treated with Vedolizumab. A large retrospective review of data from a multicenter consortium database of over 1000 Vedolizumab treated IBD patients reported CMV colitis in only 4 patients. CMV reactivation appears to be an exceptionally rare but important event in patients treated with Vedolizumab. Based on this report, patients with CVID associated enteropathy and refractory diarrhea should be carefully screened for CMV when treated with Vedolizumab. Further prospective data assessing the incidence of CMV reactivation in patients with Vedolizumab therapy is required to further define these findings. Funding Agencies None

Evaluation of association between immune modulation and incidence of CMV reactivation in Sepsis-induced immunosuppression

Background: Sepsis is characterized by dysregulated host immune response to an infection, associated with impairment in innate and adaptive immunity leading to progressive immunosuppression. Cytomegalovirus (CMV) is recognized as a serious viral pathogen in sepsis. The objective was to evaluate the association between incidence of CMV reactivation and immune alteration in sepsis-induced immunosuppression in patients with prolonged sepsis Methods and materials: Prospective observational study included critically-ill adult patients admitted to hospital ICU, who had severe sepsis defined by sepsis-3 definition and healthy controls. Patients with manifest immune-suppression due to other dieses or disorder, on steroids/transplant drug/antiviral/cancer treatment were excluded. Blood sampling was done on enrolment, further weekly until 21 d or death/discharge. CMV viremia was quantified using RT-PCR (qPCR). Analysis of lymphocyte subsets and regulatory T cells (Tregs) along with HLA-DR expression on monocytes and PD-1 expression on T lymphocyte subsets were analysed using flow cytometry Results: 25 CMV seropositive patients and 11 healthy controls were evaluated. CMV reactivation occurred in 80% (n = 20) of the patients. CMV viremia > 1000 cp/ml detected in 60% (n = 12) patients whereas, CMV viremia < 1000 cp/ml occurred in 40% (n = 8) patients at any time point. Median reactivation was 7 d. Significant T lymphopenia was observed in patients with CMV reactivation > 1000 cp/ml (p < 0.01) which consistently remained low with time. PD-1 expression on both CD4+ve (411.83 + 383.65), CD8+ve (590.08 + 591.87) T cells were elevated with time in CMV reactivated patients vs non-reactive group (CD4+ve140 + 126.72; CD8+ve154.60 + 179.84). HLA-DR expression was significantly low on monocytes in all septic patients (p < 0.01). Furthermore, we found increased percentages of regulatory T cells in CMV non-reactivated group vs CMV-reactive group Conclusion: In conclusion, sepsis-induced immune suppression, indicated by up-regulated expression of PD-1 on T cell and reduction in HLA-DR expression found to be associated with incidence of CMV reactivation in patients with severe sepsis with time. Regulatory T (Tregs) cells might be contributing to regulate response against CMV reactivation. PD-1 Blockade and immune stimulation may help restoring the part of immune function leading to improved regulation of CMV reactivation and gain immune homeostasis, which may effectively help to improve clinical management in patients with severe sepsis

CMV reactivation in allogeneic hematopoietic stem cell transplant patients receiving post-transplant cyclophosphamide.

e18533 Background: Post transplant cyclophosphamide (PTCY) has been shown to be an effective treatment for prevention of graft versus host disease (GVHD). However, this increased immune suppression rates may increase the risk of CMV reactivation. There is limited published data addressing CMV reactivation in this patient population. Additionally there is no data on the efficacy of prophylactic letermovir in the patients who have received PTCY. In this study we analyzed the incidence of CMV reactivation in patients treated with PTCY and those not treated with PTCY, as well as the efficacy of letermovir in preventing CMV reactivation in the PTCY population. Methods: We conducted a retrospective review of MUD, MRD, and haploidentical stem cell transplant patients at our institution from 1/1/2014 until 12/10/2018. We analyzed the incidence of CMV reactivation (PCR &gt; 137 DNA IU/ml), peak of CMV PCR titer and time to reactivation within the first 100 days post-transplant. Results: There were 150 patients with at least 60 days of follow-up that were included in this study. These patients were split into three groups: No post-transplant cyclophosphamide (NPTCY) (N = 64), received post-transplant cyclophosphamide (PTCY) (N = 70), and received PTCY and letermovir prophylaxis. (L-PTCY) (N = 15). The incidence of CMV reactivation was increased in the PTCY patients when compared to the NPTCY (44% vs 29%). In the NPTCY patients the donor (D) serostatus increased the risk of CMV reactivation (Recipient (R)+ D+ 73% vs R+D-36%) conversely in the PTCY group the donor CMV status did not influence reactivation rates (R+D+ 52% vs R+D- 81%). The CMV reactivation rate in the L-PTCY patients was lower when compared to the PTCY patients (21% vs 44%), additionally the L-PTCY patients had much lower peak CMV titers compared to PTCY group (445 vs 2112 IU/ml). Conclusions: This study demonstrates that there is an increased incidence of CMV reactivation in patients who receive PTCY. Additionally, the donor CMV serostatus does not appear to influence the incidence of CMV reactivation in patients receiving post-transplant CY. Although the number of patients in the L-PTCY group is small, it does appear to be an effective prophylactic treatment in patients receiving PTCY.

Prophylactic rituximab prevents EBV PTLD in haplo-cord transplant recipients at high risk

Epstein–Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD) are common and potentially fatal complications after allogeneic transplantation with mismatched donors and T-cell depletion. Haplo-cord transplantation combines a mismatched UCB graft with third-party cells. Conditioning involves thymoglobulin. EBV reactivation and PTLD were common in initial patients. As of March 2017, we administered a prophylactic dose of rituximab 375 mg/m2 pre-transplant. Among 147 patients who did not receive rituximab, the cumulative incidence of post-transplant EBV reactivation and of EBV PTLD was 13% and 8%, respectively. Among 51 who received pre-transplant rituximab, the incidences were 2% (p = .0017) and 0% (p = .04), respectively. There was no difference in time to hematopoietic recovery, in the incidence of CMV reactivation, of invasive blood stream infections or of proven or probable invasive fungal infections. Pre-transplant administration of rituximab is an effective and nontoxic intervention that drastically reduces EBV reactivation and PTLD in high-risk patients.

Spectrum of Infections with a Protocol of Dual T-Lymphocyte Suppression Using ATG and PTCy for Gvhd Prophylaxis in Allogeneic Transplants for High-Risk Hematological Malignancies

Introduction ATG and PTCy have been individually shown to reduce rates of GVHD in allogeneic transplants. We adopted a combination regimen of ATG and PT-Cy for GVHD prophylaxis in allogenic transplants for high risk hematological malignancies in our centre, to decrease the rates of acute and chronic GVHD. Objectives We analysed the spectrum of infections in patients who received this dual T lymphocyte suppression protocol. Patients and methods Reduced intensity conditioning consisted of iv Fludarabine, iv Busulphan, and low dose TBI. GVHD prophylaxis was with Thymoglobulin 4.5mg/kg total dose, PT-Cy 100 mg/kg total dose and cyclosporine. The stem cell source was G-CSF stimulated PBSCs. Results 197 patients (median age 57 y, range 19-74y) with high-risk hematological malignancies were treated with this protocol. The donor types were as follows-10/10 matched unrelated donor (MUD) in 76, 9/10 mismatched unrelated (MMUD) in 26, 10/10 matched related donor(MRD) in 43 and haplo-identical (HI) donors in 52 patients. The median follow-up in the entire cohort was 12 months. The 1year OS in the MUD, MMUD, MRD and HI groups were 75%, 50%, 63.3% and 56.7% respectively. The overall percentages of proven bacterial, viral, and fungal infections were 49%, 62% and 11% respectively (Table 1). The overall incidence of CMV reactivation was 48% and was significantly different among the 4 donor groups (p=0.00). We also observed high rates of EBV reactivation (33%) and BK cystitis (18%). There were 14 pathologically confirmed cases of post-transplant lympho-proliferative disorder (PTLD), of which 1 responded to discontinuation of immune-suppression and the rest needed treatment with Rituximab. There was one death attributed to PTLD. Infections were the primary cause of death in 18 patients (23% of deaths) and a contributory cause of death in an additional 16 patients (20% deaths). The overall incidence of grade 3-4 acute GVHD in our patients was 10.1 % and of moderate/severe NIH stage chronic GVHD was 11.6% which is low compared to conventional GVHD prophylaxis regimes. Only 10% of deaths were attributable to GVHD. Conclusion Our experience shows that dual T lymphocyte suppression with PT-Cy and ATG for GVHD prophylaxis results in low rates of acute and chronic GVHD, but is associated with high rates of infections, especially viral reactivation and PTLD.

1896. A Retrospective Cohort Analysis to Determine the Incidence of CMV Viremia and Progression to CMV Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation at an Academic Children’s Hospital

BackgroundThere are limited data on incidence of CMV reactivation and safety of anti-CMV prophylaxis in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. We aimed to describe the rate of CMV viremia in patients receiving two different prophylaxis regimens based on risk assessment. The frequency of toxicity from prophylaxis is also reported.MethodsWe assembled a single-center cohort of allogeneic HCT recipients undergoing CMV surveillance testing between January 1, 2014 to June 30, 2017. Subjects were excluded if they were CMV PCR positive in the 30 days prior to HCT. Patients were categorized as high-risk (HR) if the donor product was from a CMV positive patient and they met one of the following criteria: T cell depleted graft, cord blood transplant, or receipt of anti-thymocyte globulin or alemtuzumab. The local CMV prophylaxis pathway recommends all patients initiate standard dose acyclovir on day −7. HR patients transition to foscarnet in the first week post-transplant which is continued until enteral therapy is tolerated. They are then transitioned to valganciclovir, which is continued through day +100. Standard-risk (SR) patients continue acyclovir through day +100. Patients were followed until day +180 for these outcomes: CMV viremia, CMV disease, and CMV prophylaxis related-toxicity.ResultsThe cohort included 147 subjects with 44 developing CMV viremia (29.9%). CMV viremia was more common in HR (18/35) as compared with SR (26/112) patients (51.4 vs. 23.2%, P < 0.01). The median time to reactivation was also earlier in HR patients (9 vs. 33.5 days, P = 0.01). Only two (4.5%) patients with CMV viremia progressed to CMV disease. Toxicity requiring a therapeutic change of an antiviral prophylactic agent was more common in HR (25.7%) vs. SR (8.9%) patients. Renal insufficiency was the most common reported toxicity, followed by electrolyte wasting (figure). ConclusionHR HCT recipients had a CMV viremia rate nearly triple the SR group despite a more comprehensive prophylaxis regimen. Few subjects with CMV viremia progressed to CMV disease but toxicities from antiviral prophylaxis were common. Further investigations of novel CMV prophylaxis agents with improved toxicity profile are needed to justify CMV prophylaxis in pediatric HCT patients.Disclosures M. Hayes, Merck: Grant Investigator, Research grant. A. Newman, Merck: Grant Investigator, Research grant. C. L. K. Boge, Merck: Grant Investigator, Research grant. B. T. Fisher, Merck: Grant Investigator, Grant recipient and Research grant.

Recipient and Donor KIRs Ligands Match Prevents CMV Reactivation Post-Haploidentical T Cell-Replete Transplantation

Licensed NK cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the HLA typing of donor-recipient pairs and the KIR typing of the donors in 180 leukaemia patients to assess the predictive roles of licensed NK cells and donor-activating KIR genes on CMV reactivation post-T cell-replete haplo-SCT. Multivariate analysis showed that donor and recipient KIR ligand-ligand graft-versus-host direction or host-versus-graft direction mismatch were associated with the incidence of CMV reactivation [HR=1.663, 95%CI, 1.161-2.383, P=0.006] and refractory CMV infection [HR=2.34, 95%CI, 1.28-4.27, P=0.006] post-haploidentical T cell-replete transplantation. Donor and recipient KIR ligand-ligand match decreased CMV reactivation (51.65% [46.67, 56.62%] vs. 75.28% [70.87, 79.69%], P=0.012), refractory CMV infection (17.58% [13.77, 21.40%] vs. 35.96% [31.09, 40.82%], P=0.004) and CMV disease (3.30% [1.51, 5.08%] vs. 11.24% [8.04, 14.43%], P=0.024), respectively. Meanwhile, there was a significantly increased risk of CMV reactivation in patients who accepted a KIR2DS2-positive donor compared those who accepted a KIR2DS2-negative donor (80% [71.93, 88.07%] vs. 63.87% [60.18, 67.56%], P=0.039), especially in recipient HLA-C1/C2 and donor HLA-C1C2 with KIR2DL1/2DL2/2DL3/2DS2 genotype (100%).Conclusions: These findings suggested that donor and recipient KIR ligand-ligand match might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation. However, roles of donor positivity for the KIR2DS2 against CMV reactivation need to be further explored in T cell-replete haplo-SCT. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of the Impact of Anti-Thymocyte Globulin on Post-Transplant Outcomes in Sickle Cell Anemia Patients Undergoing BMT from HLA-Identical Sibling Donors

Introduction. Anti-thymocyte globulin (ATG) was added to the BuCy conditioning regimen to reduce the risk of rejection in patients undergoing BMT for SCA by the French group. Since then it has been widely used as part of conditioning regimens in SCD patients. However, it remains unknown whether ATG has any effect on survival in these patients. Here we compare outcome of BMT in 17 SCA patients who received Thymoglobulin (rabbit ATG, Genzyme) before transplantation to 33 patients who did not.Methods. Between July 2004 and November 2015, 50 consecutive patients of 1.7-17.1 years of age with SCA received their first BMT from HLA-identical sibling donors. Of these patients, 17 were prepared for transplantation with oral (n=5) or weight-based iv Bu Cy200 ATG 10 (ATG group) and 33 patients with Fludarabine 150 iv Bu Cy200 (non-ATG group). GVHD prophylaxis consisted of CSA/Methylprednisolone/short MTX. The two groups showed similar patient demographics. Sixty five percent of patients in the ATG group versus 6% in the non ATG group (p=0.00002) were on regular chronic blood transfusion.Results. All 50 patients had sustained engraftment. Platelet and neutrophil engraftment kinetics were similar between groups. There was no difference in the incidence of acute or chronic GVHD between the 2 groups. The incidence of grade 2-4 aGVHD in the ATG and non-ATG groups were 35% (95% CI 8-55%) and 33% (95%CI 15-48%), respectively. The incidence of grade 3-4 aGVHD was 0% in the ATG, and 20% (95%CI 4-33%) in the non-ATG group (p=0.07). The incidence of moderate or severe chronic GVHD were 11% (95% CI 0-25%) in the ATG and 22% (95%CI 5-34%) the non-ATG group (p=0.4). At the time of survival analysis, all 17 patients in the ATG group and 27 patients in the non-ATG group were alive, with median follow-up durations of 7.5 years (range, 3.9-12 years) and 3.6 years (range, 0.8-4.5 years), respectively. For all patients the probability of disease-free survival (DFS) was 87% (95% CI 73-94%). DFS was superior in the ATG group (100%) compared with the non-ATG group [79% (95%CI 60-90%)] (P=0.050) (Figure 1). In the non-ATG group 6 patients have died from severe acute or chronic GVHD-related complications.There was no significant difference in the rate of infectious complications between groups, except for a high incidence of BK virus-related hemorrhagic cystitis in the ATG group (Table 1). The incidence of CMV reactivation was high in both groups but none of the patients developed CMV disease. Two patients in the ATG and one in the non-ATG group showed EBV reactivation with low viral load and none of them developed lymphoproliferative disorder. Neurotoxicity related to cyclosporine was similar in both groups (17% vs 15%). At present all patients in the ATG group and 2 patients in the non-ATG group are off immunosuppressive medication.Conclusions. From this single center study, we report excellent DFS in SCA patients who received ATG as part of the conditioning regimen. This is the first reported study comparing outcomes after ATG-based vs non-ATG-based conditioning regimen for SCA. There was a trend, not significant (p=0.07), for less grade 3-4 aGVHD with ATG in the conditioning regimen. This study showed that the addition of fludarabine to the standard BuCy regimen was well tolerated, and successfully prevented graft rejection in SCA patients. Further study, using low dose ATG in the FluBuCy regimen to increase DFS is currently in progress. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Human Herpesvirus 6 replication predicts Cytomegalovirus reactivation after allogeneic stem cell transplantation from haploidentical donor

Background and objectivesSince HHV-6 reactivation after transplant has been reported to increase the risk of CMV infection, we tested this hypothesis in the HLA-haploidentical hematopoietic stem cell transplantation setting. Study designFrom February 2011 to October 2015, 75 patients received hematopoietic stem cell transplantation using a T-cell replete graft from a HLA-haploidentical donor at our Institution. ResultsInterestingly, 87% of HHV-6 reactivations were followed by a CMV reactivation, at a median of 15days between the two viruses. Incidence of CMV reactivation was 14.5-fold higher in those patients with prior HHV-6 reactivation vs. those without it (p-value<0.001). ConclusionThe present results suggest that HHV-6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection.

(265) - A Pre-Transplant Humoral Immunity Score to Identify Risk of Severe Infection in Heart Recipients. A Multicenter Study

s S105 Purpose: We hypothesize that by individualizing antiviral prophylaxis according to their CMV immune response, and continuing valganciclovir until CMV-specific T-cell immunity has been established the incidence of late CMV reactivation will be reduced. We provide an interim analysis of 49/130 lung transplant (LTx) patients who have completed an interventional study of CMV-specific immune monitoring to direct the length of antiviral prophylaxis. Methods: LTx recipients were randomized 1:2 to either standard of care (cessation of antiviral prophylaxis at 5 months) or the need for continued antiviral prophylaxis as determined by the QuantiFERON-CMV assay. Those with a negative result received up to an additional 6 months of antiviral prophylaxis. The primary end-point of the study will be the incidence of CMV reactivation in the lung allograft within 18 months of LTx. Monthly blood monitoring for CMV was performed for 6 months after cessation of Valganciclovir. CMV reactivation within the lung allograft was assessed at bronchoscopy performed 9, 12 and 18 months after LTx. Results: An interim analysis of 49 LTx patients (female 57%, COPD 59%, mean age 56 years, Basiliximab 29%) was performed. CMV risk profiles defined by donor (D) and recipient CMV serostaus included D+/R+ (n = 20), D+/R(n = 12) and D-/R+ (n = 17). Low level late CMV reactivation (PCR > 150 copies) was common in both the blood (43%) and BAL (55%). Adopting a QFN-CMV directed approach to antiviral prophylaxis significantly reduced the incidence of severe viremia (40% vs 6%), with a less dramatic reduction seen in the lung allograft (33% vs 21%). The magnitude of the QFN-CMV response impacted on the subsequent risk of late severe CMV viremia, that was seen in 35% of LTx patients with a QFN-CMV response 1. Conclusion: A QFN-CMV directed approach significantly reduces late CMV viremia in LTx patients. Persistent CMV reactivation within the transplanted lung suggests that conventional CMV-specific T-cells may be less effective in the MHC-mismatched allograft.

(262) - Clinical Characteristics and Outcomes of Mycobacterium abscessus Isolation in Lung Transplant Candidates and Recipients: A Systematic Review

s S105 Purpose: We hypothesize that by individualizing antiviral prophylaxis according to their CMV immune response, and continuing valganciclovir until CMV-specific T-cell immunity has been established the incidence of late CMV reactivation will be reduced. We provide an interim analysis of 49/130 lung transplant (LTx) patients who have completed an interventional study of CMV-specific immune monitoring to direct the length of antiviral prophylaxis. Methods: LTx recipients were randomized 1:2 to either standard of care (cessation of antiviral prophylaxis at 5 months) or the need for continued antiviral prophylaxis as determined by the QuantiFERON-CMV assay. Those with a negative result received up to an additional 6 months of antiviral prophylaxis. The primary end-point of the study will be the incidence of CMV reactivation in the lung allograft within 18 months of LTx. Monthly blood monitoring for CMV was performed for 6 months after cessation of Valganciclovir. CMV reactivation within the lung allograft was assessed at bronchoscopy performed 9, 12 and 18 months after LTx. Results: An interim analysis of 49 LTx patients (female 57%, COPD 59%, mean age 56 years, Basiliximab 29%) was performed. CMV risk profiles defined by donor (D) and recipient CMV serostaus included D+/R+ (n = 20), D+/R(n = 12) and D-/R+ (n = 17). Low level late CMV reactivation (PCR > 150 copies) was common in both the blood (43%) and BAL (55%). Adopting a QFN-CMV directed approach to antiviral prophylaxis significantly reduced the incidence of severe viremia (40% vs 6%), with a less dramatic reduction seen in the lung allograft (33% vs 21%). The magnitude of the QFN-CMV response impacted on the subsequent risk of late severe CMV viremia, that was seen in 35% of LTx patients with a QFN-CMV response 1. Conclusion: A QFN-CMV directed approach significantly reduces late CMV viremia in LTx patients. Persistent CMV reactivation within the transplanted lung suggests that conventional CMV-specific T-cells may be less effective in the MHC-mismatched allograft.

Use of CMV Unselected Blood Products Does Not Increase the Risk of CMV Reactivation in Patients Undergoing Hematopoetic Stem Cell Transplant (HSCT)

Introduction: Conventionally patients receiving allogeneic HSCT (AlloHSCT) have received CMV negative blood products to obviate the risk of transfusion related CMV transmission. In the era of leucodepletion with more than log 4 reduction in blood product WBC content, the utility of this practice has been questioned and, in line with SABTO (Safety of Blood, Tissues and Organs) guidance, most UK transplant centers have adopted the policy of using unselected blood products for this patient cohort. At this center, our policy was changed to conform to recommended national practice in April 2013. This analysis was carried out to evaluate if this change has resulted in an increased incidence of CMV reactivation.Methods: 868 (M: 561; median age: F: 307; median age:) patients who received HSCT from January 1998 to November 2014 were included in analysis. Transplant types included AutoHSCT (n=384), AlloHSCT-Sibling (n=217) and AlloHSCT-MUD (n=267). Diagnosis was Ac Leukaemia (n=313), Chr Leukaemia (n=36), Myeloma (n=216), Lymphoma (n=261) or other malignancies (n=42). Commonest indication for AutoHSCT was myeloma or lymphoma. TBI based condition was used in 225 AlloHSCT and 50 AutoHSCT cases. RIC was used in 268 cases and full intensity in 215 cases (unknown in 1). Alemtuzumab or ATG was used in conditioning for 274 cases. Source of stem cell was PBSC (AutoHSCT: 363, AlloHSCT: 382), BM (AutoHSCT: 7, AlloHSCT: 97), both (AutoHSCT: 2, AlloHSCT: 9) and 8 AlloHSCT were UCB grafts.Results: 26, 345 blood PCR results were evaluated. 3100 tests were requested in AutoHSCT patients and 109 (3.6%) were positive. There were no differences in the incidence of positive CMV PCR results before and after use of CMV unselected blood products. Further analysis was limited to AlloHSCT patients. AlloHSCT patients were divided in two groups, GrpA: 1998 to 2013 and GrpB: 2013 to 2014 to evaluate the effect of using CMV unselected blood products. In AlloHSCT group, 9.1% of 23278 samples tested for CMV PCR were positive (Median log: 2.7, range: 0.3-7.3). Incidence of CMV reactivation was not different in GrpB as compared to GrpA (47.7% vs. 48.1%, p=0.93). There was no difference with gender (M: 45.8% vs. F: 53.1%, p=0.13), type of donor (Sibling: 48.6% vs. MUD: 47.9%, p=0.98), use of Alemtuzumab/ATG (50.6% vs. 45.4%, p=0.51), source of stem cells (BM: 36.4% vs. PBSC: 51.3%, p=0.07), use of TBI (43.8% vs. 52.3%, p=0.06). Higher incidence was observed with use of RIC transplant (53.2% vs. 42.3%, p=0.02) and donor-recipient CMV mismatch (NP: 24.5%, PN: 80%, PP: 90.8%, p<0.0001).Conclusion: This analysis suggests that the risk of CMV reactivation is related to the donor-recipient CMV mis-match and the transplant intensity. Use of CMV unselected blood products does not increase the risk of CMV reactivation and careful selection of donors using CMV sero-status is the key factor to reduce the risk of CMV reactivation post AlloHSCT. DisclosuresCavet:Janssen: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Somervaille:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Comparison of Two Doses of Antithymocyte Globulin (ATG) in Reduced Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)

Introduction: The appropriate dose of antithymocyte globulin (ATG) to be used in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is yet to be determined. In our previous retrospective analysis we compared two dosing schedules of ATG (7.5 mg/kg vs 6 mg/kg) in 136 patients who had undergone RIC allo-HSCT, and found no significant differences in the incidence of acute or chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse, progression-free survival (PFS) or overall survival (OS). As of October 2013, our ATG dosing was lowered from 6.5 to 4.5 mg/kg. We now compare the outcomes of patients who received ATG at a dose of 4.5 mg/kg (r-ATG) to 6 mg/kg (R-ATG)Methods: We retrospectively analyzed the outcomes of patients who underwent unrelated or mismatch related RIC allo HSCT for hematologic malignancies and received r-ATG (40 patients) vs R-ATG (216 patients) at The Ohio State University Comprehensive Cancer Center between October 2007 and September 2014. Cumulative incidences of GVHD, infection, NRM, and relapse were analyzed using Gray's test, accounting for competing risks. PFS and OS were analyzed using the log-rank test.Results: Patients with hematologic malignancies included AML/MDS (53%), NHL/Hodgkin's (19%), CLL (12%), and other hematologic malignancies including ALL (16%). There was a significant association between disease group and ATG dose (p<0.001), with none of the patients diagnosed with CLL receiving r-ATG and a higher percentage of those with other malignancies receiving r-ATG vs R-ATG than expected. Secondary to the imbalance in disease groups, those receiving r-ATG were younger (median 50 vs 59 yrs, p=0.01) and more likely to have bone marrow stem cell source (18% vs 5%, p=0.008). There were no significant differences in recipient or donor sex, degree of HLA match, prior autografts, comorbidity index, donor/recipient CMV status and CD34 cell dose between the two groups. The cumulative incidences of acute GVHD grade II-IV at day 180 in the r-ATG and R-ATG groups were 63% and 44% (p=0.009), and of grade III-IV 18% and 11% (p=0.25) respectively (Figure 1A and B). When controlling for differences in underlying disease, the estimated risk of acute GVHD grade II-IV was 1.6 times higher with r-ATG (p=0.04). The respective cumulative incidences at 6 months of chronic GVHD were 14% and 16% (p=0.65), and of extensive chronic GVHD 14% and 13% (p= 0.29). With limited follow-up in patients receiving r-ATG (median 10 months), significant differences were not observed in longer-term outcomes between the two groups including relapse rate (p=0.83), NRM (p=0.91), PFS (p=0.92), and OS (p=0.996). The incidence of CMV reactivation at day 180 was lower in the r-ATG group (5% vs 26%, p=0.005), though the incidence of competing risks including GVHD, relapse and death prior to documented reactivation was higher in the r-ATG group (p<0.0001). No statistically significant differences were seen in Epstein-Barr virus reactivation (p=0.74), BK-virus associated hemorrhagic cystitis (p=0.79), bacterial infections (p=0.11), or Clostridium Difficile infections (p=0.22).ConclusionsWhile there was an increase in grade II-IV acute GVHD with r-ATG, there was no significant difference in acute GVHD grade III-IV, relapse, NRM, PFS and OS between the two cohorts. r-ATG resulted in a lower proportion of CMV reactivation, but in a higher proportion of other competing risks. Given the increasing use of RIC allo-HSCT for treating malignant hematologic conditions, the correct dose and schedule of ATG administration should be defined by prospective randomized controlled trials. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Incidence of CMV Reactivation and Infection in Children and Adolescents Following Allogeneic Hematopoietic Stem Cell Transplantation in High CMV Exposure Population

s / Biol Blood Marrow Transplant 21 (2015) S240eS265 S253 (10.3%) were attributed to bacterial infection. Risk factors associated with higher risk of bacterial infections included age < 2 years at transplantation (p1⁄40.001), use of PB (p1⁄40.038), myeloablative conditioning (p1⁄40.027), mismatched or unrelated donor (p1⁄4 0.002), family donors other than identical siblings (p1⁄40.046), use of TPN (p1⁄40.046), and morphine use for more than 5 days (p1⁄40.011) due to significant mucositis. In a multivariate analysis; age at transplantation < 2 years (HR1⁄46.834; 95% CI 1.528-30.572; p1⁄40.0119) was the only factor associated with higher risk for bacterial infection post HSCT. Conclusion: Bacterial infections are common following allogeneic HSCT in children and adolescents not receiving antibiotic prophylaxis and are associatedwith significant risk of mortality. Children below 2 years of age are at higher risk. We have prospectively implemented an antibiotic prophylaxis regimen in an effort to decrease bacterial infections.

Mycophenolate Compared to Methotrexate As Part of Cyclosporine Based-GVHD Prophylaxis Does Not Affect Transplant Outcomes, Reduces Organ Specific Acute And Chronic GVHD, but Increases The Risk of CMV Viremia In Matched Related Donor Peripheral Blood Stem Cell Transplantation

IntroductionGraft versus host disease (GVHD) remains the most frequent and serious complication following allogeneic hematopoietic stem cell transplantation (HSCT). There is marked variability in GVHD prophylaxis regimens but the most commonly used is methotrexate (MTX) in combination with cyclosporine (CSA). However MTX toxicity can mandate dose reductions resulting in an increased risk of acute GVHD (aGVHD). There is limited and conflicting data on the efficacy of mycophenolate (MMF) in comparison to MTX. Methods and patientsWe retrospectively reviewed 242 consecutive patients who received related donor myeloablative peripheral blood stem cell transplantation between 2002 and 2012 at the Princess Margaret Cancer Centre, Toronto Canada. We compared patients who received MMF/CSA (n=71) (institutional standard of care since 2009), to a historical control who received MTX/CSA (n=171). MTX was given IV as 15 mg/m2 on day +1, and 10 mg/m2 on days +3, +6, and +11 post HSCT with adjustments made for mucositis, renal and liver dysfunction and effusions. MMF was given as 45mg/kg/day in 3 divided doses orally from day 0 to +30 post HSCT. In both GVHD prophylaxis regimens the CSA strategy was the same (5 mg/kg/day IV q12h starting day -1 aiming for therapeutic trough levels between 200-400 mcg/L). Routine surveillance of CMV viremia was performed using pp65 antigenemia (>1 positive cell) until 2011 and thereafter this was performed using PCR (>200 copies). There were no differences in patient characteristics except for age and conditioning regimens due to period effect and institutional changes in practice. ResultsThere was no difference between the MTX/CSA and MMF/CSA groups in 3-year overall survival (66.1% vs 56.9%, p=0.09), 3-year non-relapse mortality (19.0% vs 27.4%, p=0.13) and relapse (15.5% vs 16.0%, p=0.56). Patients in the MMF/CSA group had significantly faster neutrophil and platelet engraftments: medians of 13 vs 18 days and 10 vs 14 days respectively (p<0.001). The cumulative incidence of aGVHD (grades 2-4) was significantly higher in the MTX/CSA group 74.4% vs 45.1% (p<0.001). There was no difference in the incidence of gut aGVHD but there was a higher incidence of skin (71.5% vs 51.5% p<0.001) and liver (53.0% vs 11.3% p<0.001) aGVHD in the MTX/CSA vs MMF/CSA groups. There was no difference between the two groups in the 5-year cumulative incidence of chronic GVHD (cGVHD) or gastrointestinal, liver or skin cGVHD. There was however, a significantly lower incidence of lung, eye and mouth cGVHD in the MTX/CSA group: 29% vs 46.8% (p=0.04) for lung cGVHD, 37.7% vs 71.5% (p<0.001) for eye cGVHD and 59.6% vs 72.8% (p=0.001) for mouth cGVHD. The incidence of CMV reactivation was significantly lower in the MTX/CSA group, 40.9% vs 58.1% (p<0.001) in the MMF/CSA group. In multivariate analysis MMF/CSA was identified as an independent favorable factor for aGVHD (p=0.001, HR 0.62) but as a significant risk factor for CMV reactivation (p=0.005, HR 1.94). ConclusionThe use of MMF/CSA in MRD PBSC transplant is not inferior as GVHD prophylaxis in comparison with MTX/CSA. MMF/CSA is associated with faster engraftment but a higher risk of CMV reactivation. Disclosures:Off Label Use: Mycophenoplate compared to methotrexate as part of cyclosporine based graft versus host disease prophylaxis.

A Novel Treatment Protocol Successfully Prevented Graft Rejection and Improved Disease-Free Survival in Class 3 Children with Thalassemia

Abstract 150▪▪This icon denotes a clinically relevant abstract Background:Historically, bone marrow transplantation (BMT) in class 3 thalassemia patients has been associated with a significant risk of graft failure and transplant-related mortality leading to lower disease-free survival. Our initial study showed that class 3 patients treated with a new treatment protocol (Pc 26) had an improved survival and decreased rejection rates compared with previous protocols (Blood 2004;104:1201). An interim analysis of our subsequent experience with BMT in class 3 patients treated with Pc26 showed an increased rejection rate which has prompted us to modify the protocol to overcome this complication. Since February 2007 we have been using the modified Pc26 (Pc26m) in class 3 patients. Patients and Methods:Between June 2004 and July 2011 a total of 45 class 3 patients with median age of 10 years (range, 5–16) were treated: 26 patients with original (Pc26) and 19 patients with modified protocol (Pc26m). The two groups were well balanced in respect to baseline demographic and clinical characteristics. Patients had severe iron overload with median serum ferritin and liver iron concentration of 2626 ng/mL (range, 777–10222) and 20,8 mg/g dry weight (range, 5–40.7), respectively. Median liver fibrosis score was 2 (range, 1–5). There were 5 patients with HCV, and 1 with hepatitis B virus (HB Ag-positive) at the time of transplantation. The median number of packed RBC transfusions was 140 units (range, 25–307). The Pc26m consisted of pre-conditioning and conditioning phases. This novel treatment regimen involved an intensified preparation with 3 mg/kg of azathioprine and 30 mg/kg hydroxyurea daily from day -45 from the transplant, fludarabine 30 mg/m2 from day -16 through day -12, followed by the administration of weight based busilvex (since 2006), Thiotepa 10 mg/kg/day and CY 160 mg/kg total dose. GVHD prophylaxis consisted of CSA, low-dose methylprednisolone, and a modified “short course” of methotrexate (MTX). Results:Four of 26 patients treated with Pc26 and none of 19 patients treated with Pc26m had graft failure. The median time of neutrophil recovery (ANC>500 ×109/L) and platelet recovery (>20 ×109/L) were similar in both group of patients. Transplant outcomes are shown in Table 1.Table 1Transplant outcomesPc26Pc26mPNumber of patients2619Overall survival85% (95%CI 67–94)84% (95%CI 61–94)Disease-free survival74% (95%CI 52–88)84% (95%CI 61–94)0.43Rejection16% (95%CI 5–33)00.08Acute grade 2–4 GVHD46% (95%CI 26–64)32% (95%CI 13–53)0.34Complete donor chimerism at 2 months, n2217Mixed chimerism at 2 months, n1 (83% donor cells)1 (89% donor cells)Death, n43Causes of deathGVHD(1), splenectomy(1), pneumonia(2)GVHD(1), ileus (1), unknown (1 at home)Median follow-up, month59 (52–83)40 (7–49)Overall treatment protocol was well tolerated without any significant toxicity. None of the patients had grade 4 toxicity. Most frequent grade 3 toxicity was AST and ALT elevations. Five patients, 3 treated with Pc26 and 2 with Pc26m had grade 2 hemorrhagic cystitis. One patient in each group had moderate liver VOD resolved with supportive care. Two patients in Pc26 group and one in the Pc26m group had pneumonia. There were 3 patients with bacteremia: 2 in Pc26 and one in Pc26m treated patients. The incidence of CMV reactivation was similar in both group. Conclusion:This study shows that the modified treatment protocol for class 3 thalassemia patients is highly effective in terms of graft failure leading to a high DFS rate which is comparable to those obtained in class 1 and class 2 patients. It also suggests that this intensified preparative regimen aimed at reducing a large disease burden and increasing immunosuppression over time thus avoiding unacceptable peritransplant drug toxicity is essential for minimizing graft failure in these high-risk patients. Disclosure:No relevant conflict of interest to declare. Disclosures:No relevant conflicts of interest to declare.

The Bidirectional Relationship Between Cytomegalovirus Replication and Graft-Versus-Host Disease - a Retrospective Single Center Study.

Abstract 2236Poster Board II-213Cytomegalovirus (CMV) infection and graft-versus host disease (GVHD) are important complications after allogeneic HSCT with a clear link. Multiple studies show that GVHD and its treatment put patients at risk for CMV reactivation. Data on CMV infection as a cause of GVHD, in contrast, are controversial. The association of pre-transplant CMV serology with GVHD development and reduced rates of chronic GVHD after preemptive CMV treatment are indicative of such an association. However, analyses of the direct impact of CMV infection on GVHD are rare; a recent small study found no effect of CMV replication on subsequent development of acute GVHD (Wang et al, BMT 2008). We analyzed in a single centre study the association of CMV reactivation with acute GVHD in 517 patients treated between 1993 and 2008. 59% of patients were male, median age was 42 years (range 16 to 70). Diagnoses were AML (31%), ALL (16%), CML (15%), MDS/MPN (13%), lymphoma (21%), and other (4%). Conditioning regimens were Cy/TBI ±/- etoposide (49%), Cy/Bu (17%), fludarabine and TBI (16%), or others (18%). GVHD prophylaxis consisted of CyA/MTX (78%) or CyA/MMF (21%). Donors were HLA-identical siblings (65%), other family members (4%), or unrelated donors (31%). We made use of a standardized CMV policy over the last decades. CMV reactivation was monitored using real-time polymerase chain reaction or pp65 antigenemia assay weekly in patients without infection, twice weekly in patients with CMV replication. CMV was preemptively treated with gancyclovir or foscarnet. To determine the correlation of CMV infection with acute GVHD, we used a stringent Cox regression model, in which CMV replication was modeled as a time-dependent covariate becoming positive on the day of the first detection of CMV and negative on the first negative assay thereafter. Multiple episodes of CMV replication were considered. Acute GVHD was modeled as a time-dependent covariate in models with CMV infection as endpoint. Hazard ratios (HR) were adjusted for patient age, disease, disease stage, donor type, stem cell source, conditioning regimen and GVHD prophylaxis. The analysis was restricted to the time from transplant to day 100. CMV reactivation was detected at least once in 16% (84/517) of patients at a median of 33 (range 1-95) days after HSCT. Median duration of CMV reactivation was 8.5 days (range 2-62). 19 patients showed multiple episodes of CMV replication. Donor and recipient serostatus significantly influenced the day 100 cumulative incidence of CMV infection: D-/R- (N=173) 6%; D±/R- (N=61) 10%; D±/R± (N=128) 25%; and D-/R± (N=99) 37%, p<0.001. The cumulative incidence for any acute GVHD (grade I-IV) was 67% (95% CI 56-78%) with a median onset time at day 14 (range day 5-94); the cumulative incidence for severe acute GVHD (grade II-IV) was 48% (95% CI 40-56%). When both endpoints (CMV, GVHD) were combined, 150 patients (29%) experienced neither GVHD nor CMV reactivation, 281 (54%) GVHD only, 19 (4%) CMV reactivation only, and 67 (13%) both CMV reactivation and GVHD. Of the 67 patients with both GVHD and CMV, 46 (69%) developed GVHD prior to CMV reactivation, 17 (25%) developed GVHD during CMV reactivation, and 4 (6%) developed GVHD after CMV reactivation. Cox modeling revealed that presence of GVHD grade II-IV increased the risk of CMV infection (HR 1.61, 95% CI 1.03-2.52, p=0.04). Similarly, patients were at increased risk of developing acute GVHD during phases of CMV replication (grades I-IV: HR 2.23, 95% CI 1.39-3.81, p=0.001; grades II-IV: HR 2.00, 95% CI 1.08-3.72, p=0.03). GVHD grade was not influenced by concomitant CMV reactivation (median grade II, in patients with or without CMV reactivation). The overall proportion of GVHD that occurred during phases of CMV replication was small (3% versus 64% occurring in CMV non replicating patients). Even if GVHD occurring after resolution of CMV reactivation was additionally taken into account, the majority of GVHD occurred without preceding CMV infection (63% versus 4%). These data describe the complex relationship between CMV infection and GVHD. We confirm previous studies that GVHD (and GVHD therapy) can induce CMV infection. We describe as well that patients with active CMV replication have a significantly higher risk of developing GVHD compared to patients without CMV replication. However, the proportion of GVHD that could be linked to CMV reactivation was small in this population with a low overall incidence of CMV reactivation. Disclosures:No relevant conflicts of interest to declare.

Higher Incidence of CMV Reactivation in CMV Seropositive Recipients Following Fludarabine Based Reduced Intensity Conditioning Transplants – A Retrospective Comparison with Myeloablative Transplants

Higher Incidence of CMV Reactivation in CMV Seropositive Recipients Following Fludarabine Based Reduced Intensity Conditioning Transplants – A Retrospective Comparison with Myeloablative Transplants