Allogeneic Hematopoietic Stem Cell Transplantation Recipients Research Articles

Bone Health Screening and Treatment in Allogeneic Hematopoietic Stem Cell Transplant (HCT) Patients

Bone density loss is a well-recognized and common complication in allogeneic HCT recipients. Guidelines recommend screening with dual photon densitometry at 1 year post-HCT, and counseling of patients on preventative strategies along with consideration of treatment for patients at high risk for bone loss. However, osteoporosis and fragility fractures remains a major cause of morbidity, and significantly impacts the quality of life of allogeneic HCT survivors. Given the high morbidity of bone density loss in our patients, we sought to create specific guidelines, taking a more proactive approach to bone health within our program. In collaboration with the Cleveland Clinic Rheumatology department, pharmacists, and the Blood and Marrow Transplant Survivorship Program, we created specific guidelines for screening, prevention and treatment of bone loss post HCT. Given the high prevalence of older adults, pre-disposing co-morbidities and steroid use, we have initiated pre-transplant screening including Vitamin D levels and dual-energy X-ray absorptiometry (DEXA) scans on all patients during their evaluation. Patients with a history of prolonged systemic steroid use defined as ≥ 7.5 mg daily for ≥3 months are treated pre-HCT regardless of their DEXA or applied fracture risk assessment tool (FRAX) score. The DEXA and applied FRAX scores are used to determine prevention and treatment strategies for all other patients. We recommend repeat DEXA 1-year post-HCT, and recommend treatment in patients who have graft-versus-host disease requiring systemic corticosteroids (>7.5 mg prednisone equivalent for >3 months), have osteopenia or osteoporosis with a DEXA T-score of ≤ -1.0 or FRAX score (hip >3%, MOP >20%). Treatment recommendations consists of bisphosphonate therapy, yearly dosing of zolendronic acid for at least 3 years, and continuation of therapy for high risk patients (older women, vertebral fractures, low hip T-score or high FRAX score, previous major fracture, or who fracture on therapy, and continuous use of steroids). Oral bisphosphonates are considered for patients with good compliance and oral absorption. Denosumab is considered for patients with poor renal function. We provide an example of a systematic multidisciplinary approach to assess, prevent and manage bone loss in allogeneic HCT recipients. Study of patient tolerance and prevention of bone density loss in this high risk patient population with this algorithm compared to past practices is ongoing.

The Economic and Health Utilization Cost of Clinically Significant Cytomegalovirus Infection Following Allogeneic Hematopoietic Cell Transplantation

Introduction Understanding the economic impact of managing allogeneic hematopoietic stem cell transplant (HCT) recipients with cytomegalovirus (CMV) is important for future planning within institutional transplant programs. CMV remains the most frequent viral infection following HCT but less is known about the impact of CMV on health resource utilization. Objectives We aimed to evaluate the economic burden of CMV infection in a large HCT centre operating under a universal health care system. Methods A retrospective single centre study at the Royal Melbourne Hospital, Australia was performed on all allogeneic HCT recipients between Jan2015 to Dec2017. CMV pre-emptive monitoring using quantitative CMV viral load was performed from time of transplant to 100 days or longer if GVHD. Clinically significant CMV (csCMV) was defined as viremia requiring anti-CMV treatment. First line anti-CMV therapy was (val)ganciclovir and second-line therapy was foscarnet. Hospital costing data for all admissions in the first 12 months were obtained. Financial year costing was available for FY2015/2016 to FY2017/2018. Ethics was approved by the Melbourne Health Human Ethics Review Committee (HREC 2017.368). Results A total of 255 patients underwent alloHCT with a median age of 51 years (IQR 40-59). The most common underlying diagnosis was AML (41%) and 54% had unrelated donor transplants. Pre-transplant recipient CMV seropositivity was 62% (n=158), of whom 139 had detectable CMV viremia and 105 (41.2%) experienced clinically significant CMV (csCMV). The median duration of CMV treatment was 33 days (IQR 21-63). Re-admission to hospital within the first 12 months of HCT occurred in 78.4%. There was a greater number of admissions observed in csCMV patients compared to no csCMV (median 3 vs 2, p=0.001) with the duration of admitted days within the first 12 months being significantly greater in csCMV patients compared to no csCMV (median 65 vs 36 days, p Conclusion The health care cost and resource utilization of treating CMV infection following an allogeneic HSCT is substantial and places a heavy burden on limited health resources. In this study, patients experiencing csCMV had an increased number and longer total duration of admissions days compared to patients who did not require CMV treatment. Interventions aimed at reducing the burden of CMV in alloHCT recipients are required.

Enteral Vancomycin Is Effective Clostridium Difficile prophylaxis in Pediatric, Adolescent, and Young Adult Hematopoietic Stem Cell Transplant Recipients

Background Clostridium difficile infection (CDI) is a major source of morbidity for patients undergoing autologous and allogeneic hematopoietic stem cell transplantation (HSCT). CDI can complicate gastrointestinal mucositis, lead to mucosal barrier infections or sepsis, and compromise nutrition after HSCT. CDI may contribute to acute gastrointestinal graft-versus-host disease (GI aGVHD) and reduce overall survival in allogeneic HSCT patients. Use of enteral vancomycin as CDI prophylaxis may reduce morbidity and improve outcomes in HSCT recipients. Methods As a quality improvement initiative, enteral vancomycin was instituted as CDI prophylaxis in all autologous and allogeneic HSCT recipients at Methodist Children's Hospital beginning 02/13/19. Patients were prescribed vancomycin 125 mg oral/enteral twice daily (Ganetsky et al. Clin Infect Disease 2019; 68 (12):2003-2009) from HSCT admission to discharge home. Patients readmitted during the first 100 days after HSCT resumed enteral vancomycin while hospitalized. Physicians, advanced practice providers, and pharmacists monitored enteral vancomycin administration. The infectious disease and prevention team monitored CDI and weekly vancomycin resistant enterococcus (VRE) stool testing per institutional policy. Pre- and post-implementation data was retrospectively reviewed (number of HSCT patients, CDI, VRE, adverse events of enteral vancomycin, and GI aGVHD). Two-sided Fisher's exact test was used to compare CDI before and after institution of enteral vancomycin prophylaxis. Results Between 01/05/2018 and 02/12/2019, the rate of CDI was 29% (n=9/31). After implementation of CDI prophylaxis (02/13/19 to 09/16/19), the rate of CDI was 0% (n=0/23). Enteral vancomycin resulted in a significant reduction in the number of CDI cases (p=0.0068). Prior to implementation of CDI prophylaxis, 26% (n=7/27) of allogeneic HSCT recipients developed GI aGVHD. Of the 7 patients that developed GI aGVHD, 6 had a history of CDI. After implementation of CDI prophylaxis, 7% (n=1/14) of allogeneic HSCT recipients developed GI aGVHD. There were no VRE positive screens or infections. There were no adverse events related to enteral vancomycin. Conclusions Enteral vancomycin appears to be safe and effective CDI prophylaxis in pediatric, adolescent, and young adult HSCT recipients. Since institution of enteral vancomycin prophylaxis, there has been a significant reduction of CDI in our HSCT patients. This quality improvement project is ongoing and future analyses will compare GI aGVHD and overall survival with CDI pre- and post-implementation of enteral vancomycin prophylaxis.

Economic Burden of Cytomegalovirus infection in CMV-Seropositive Hematopoietic Stem Cell Transplant Recipients Managed with Pre-Emptive Therapy: A Single Center Experience

<h3>Introduction</h3> <i>Cytomegalovirus</i> (CMV) infection is a common viral infection in allogeneic hematopoietic stem cell transplantation (HCT) recipients, especially in the first 100 days post HCT. Preemptive therapy (PET) proved to be effective in managing CMV but led to prolonged antiviral use and associated toxicities. Limited data exist on the economic burden of PET use and cost of care among HCT recipients. <h3>Objectives</h3> We aimed to compare direct all-cause or CMV-related inpatient healthcare resource use and costs in those who received or did not receive PET through 180 days (D180) post HCT. <h3>Methods</h3> Study cohort comprised of adults, CMV R+ allogeneic HCT recipients of first peripheral blood or marrow allograft at a single center from 3/2013 to 12/2017. HCT recipients were routinely monitored for CMV using quantitative PCR assay and administered PET as per the standards of care. Data on clinical characteristics, CMV outcomes, PET administration, reasons and dates of hospitalizations were extracted from the electronic medical records. Inpatient hospital charges were obtained from the Vizient billing database from date of HCT to D180 post HCT. Charges data were converted to costs using cost-to-charge ratios, wage index and inflation rate to 2017 US Dollars. CMV-related readmissions were identified as readmissions for initiation of PET, work up or management of CMV End Organ Disease and any readmission where PET was initiated during D180 post HCT. <h3>Results</h3> Of 368 HCT recipients, 176 (48%) received unmodified graft from matched related or unrelated donors (low CMV risk); and 192 (52%) received either ex vivo T-cell depleted or conventional graft from mismatched donors (high CMV risk). Overall, 208 (57%) HCT recipients received PET; and 72% of them were high risk. PET recipients had longer length of stay for index admission (p=0.0001) and a greater proportion required readmission at D180 (p=0.00005) (Table 1); greater average inpatient costs for index admission ($184,230 vs. $150,938, p=0.0304) and for readmissions through D180 ($105,676 vs. $51,444, p=0.0032) (Table 1) as compared to those who did not receive PET. PET recipients also had higher costs for CMV-related readmissions per episode than non CMV-related readmissions ($167,701 vs. $96,941, p=0.0089) (Table 1). CMV-related readmissions comprised of 37% of total all-cause readmissions and incurred 49% of total all-cause readmission costs in PET recipients (Figure 2). <h3>Conclusion</h3> PET recipients had higher overall inpatient resource use and costs as compared to those who did not receive PET. CMV-related readmissions had disproportionate share of total inpatient readmissions costs in PET recipients. Future studies are needed to examine the cost-effectiveness of alternative strategies for CMV management.

Prevalence and Biobehavioral Predictors of Early and Long-Term Fatigue Following Hematopoietic Stem Cell Transplantation

Fatigue is a commonly reported quality of life concern after hematopoietic stem cell transplant (HSCT). Fatigue severity, duration, and interference with daily activities were evaluated at post-transplant milestones during acute recovery and through 6 years post-HSCT. We also investigated whether disease and treatment factors (allogeneic or autologous graft, diagnosis, treatment regimen), inflammation, and psychological symptoms during the peri-transplant period predicted early and long-term fatigue. Participants were 433 (191 allogeneic, 242 autologous) HSCT recipients who completed measures of fatigue (FSI), depression and anxiety (IDAS) pre-HSCT, and 1, 3, and 6 months, and 1, 3, and 6 years post-HSCT. A subset (n = 210) provided blood samples during the first 6 months post-HSCT for determination of circulating cytokine levels (IL-6, TNFα, IL-10). The majority of participants reported clinically significant fatigue at 1 (83.9%), 3 (68.4%), and 6 months (64.7%) post-HSCT. Mixed effects regression models evaluated predictors of fatigue during early recovery. Allogeneic HSCT recipients showed a slower recovery, reporting more fatigue than autologous HSCT recipients at 3 and 6 months post-HSCT, but comparable fatigue at other points (interaction z=2.99, p=0.003). No other disease or treatment factors predicted fatigue. After covarying for transplant type and patient age, higher IL-6, TNFα and IL-10 levels (all p

Incidence and Outcomes of Patients with Thrombotic Microangiopathy after Transplant: Results of Prospective Screening through a Multi-Institutional Collaborative

<h3>Background</h3> Thrombotic microangiopathy (TMA) is a severe complication of hematopoietic stem cell transplant (HSCT). <h3>Objective</h3> To determine incidence, risk factors and outcomes for patients who develop TMA following HSCT. <h3>Methods</h3> All patients were prospectively screened for TMA at participating centers with daily CBC, renal panel, and blood pressure; twice weekly LDH; and weekly urine analysis, including urine protein to creatinine ratio, from the start of the preparative regimen through the first 30 days. All labs were transitioned to weekly from day +30 to +100. TMA was diagnosed if (1) pathologic evidence of TA-TMA (e.g., renal biopsy with evidence of TMA), <i>or</i> (2) if meeting laboratory/clinical markers diagnostic for TMA (Figure 1). Each site retrospectively reviewed the data from screened patients from their respective center, and these data were aggregated to determine outcomes. <h3>Results</h3> 589 consecutive patients received TMA screening at the 12 participating centers from May 1, 2016 through June 30, 2018. TMA was diagnosed in 10% (20 of 198) of autologous and 21% (85 of 391) of allogeneic HSCT recipients. Patients undergoing HSCT for an underlying immune deficiency or bone marrow failure syndrome had a significantly higher rate of TMA (p=<0.001) (Figure 2). TMA was diagnosed at a median of 32 (IQR 24-44) days post-HSCT. Patients with TMA had a higher need for intensive care admission (46% vs. 17%, p=0.0001); increased incidence of respiratory failure (19% vs. 7%, p=0.0001); and increased incidence of bloodstream infections (44% vs. 22%, p=0.0001) in the first 100 days versus patients not diagnosed with TMA. Patients with TMA averaged significantly more days inpatient during the first 100 days than those without TMA (65 +/-27 vs. 41 +/-22 days; p=0.001). Further, patients with TMA averaged significantly more days in the ICU during the first 100 days than those without TMA (10 +/-20 vs. 3 +/-11 days; p=0.001). Six-month non-relapse mortality was significantly higher in the TMA group (19/105,18% vs. 19/484,4%; p=0.0001). Finally, six-month overall survival was significantly decreased in patients with TMA (84/105, 80% vs. 453/484,94%; p=0.0001) (Figure 3). In patients diagnosed with TA-TMA, 49 (47%) were treated with eculizumab and 3 (3%) received plasmapheresis. <h3>Discussion</h3> In this multi-center cohort we demonstrate a high incidence of TMA after pediatric HSCT through prospective screening. Patients with TA-TMA have higher morbidity and mortality when compared to patients without TA-TMA.

Invasive Atypical Mycobacterial Infection in Allogeneic Pediatric HSCT

<h3>Introduction</h3> Infection is a major cause of morbidity and mortality following hematopoietic stem cell transplant (HSCT). Atypical or nontuberculous mycobacterial (NTM) infections are known to occur at higher rates in patients with a compromised immune system and a study by Unal et al. reported a 6.4% incidence of NTM infections in pediatric allogeneic HSCT recipients. Disease severity with NTM infections is broad and can range from asymptomatic line infections to disseminated disease. Antimicrobial therapies for NTM infections are variable and typically multiagent. Limited data are available describing the impact of these infections and their associated therapies on HSCT outcomes in children. <h3>Methods</h3> We retrospectively reviewed outcomes for pediatric allogeneic HSCT recipients between 2014 and 2019 whose courses were complicated by symptomatic invasive NTM infection. Metrics analyzed include underlying disease, conditioning regimen, antimicrobial therapies, survival and donor engraftment. <h3>Results</h3> 5 patients were diagnosed and started on multidrug therapy for NTM surrounding HSCT. Presenting symptoms for each patient are described in Figure 1. Patient demographics and NTM details are shown in Table 1. All 5 patients received myeloablative conditioning (MAC) with busulfan and fludarabine, in addition to thiotepa (n=1), ATG (n=1) and alemtuzumab (n=1) in select patients. All patents engrafted ≤ 20 days with at least 99% donor chimerism. Patient 3 showed mixed chimerism on day 25, eventually resulting in graft loss requiring re-transplantation. Four out of five patients (80%) are alive today with median follow up time of 4.3 years (range 3.4 – 5.3 years). <h3>Conclusion</h3> Our experience suggests that children undergoing HSCT complicated by NTM infections have favorable outcomes. NTM directed multi-drug therapy was well tolerated and did not immediately appear to affect engraftment. Recurrence of symptomatic invasive NTM infection occurred in two patients post-HSCT after stopping NTM therapy, while a third patient developed a first-time symptomatic invasive NTM infection after HSCT. This observation advocates for continuation of antimicrobial therapy through immune reconstitution.

Clinical trajectories, healthcare resource use, and costs of long-term hematopoietic stem cell transplantation survivors: a latent class analysis.

To identify patterns of healthcare utilization in allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients and evaluate factors associated with high-need and high-cost post-transplantation care. Latent class analysis of a retrospective cohort of long-term allogeneic (n = 436) and autologous (n = 888) HSCT survivors within the Truven MarketScan database (2009-2014). We assessed factors associated with the latent classes by comparing post-transplantation healthcare utilization including inpatient admissions and length of stay, emergency room visits, specialist visits, and primary care provider visits. Four utilization classes were identified in allogeneic and autologous HSCT recipients: (i) outpatient specialist care dominant (51.8% and 57.3%), (ii) outpatient primary care dominant (10.3% and 25.7%), (iii) outpatient/inpatient balanced (20.6% and 13.5%), and (iv) inpatient dominant (17.2% and 3.5%). Mean monthly healthcare expenditures in the inpatient dominant utilization class were $41,097 and $25,556 for allogeneic and autologous survivors, respectively, which were two to five times higher compared with other classes during the 2-year post-transplantation period. Factors associated with the high utilization class were transfusion (OR = 1.87, 95% CI 1.06-3.30) and 100-day post-transplant graft-versus-host-disease (OR = 1.76, 95% CI 1.05-2.94) in allogeneic HSCT; higher baseline Charlson comorbidity index (OR = 1.45, 95% CI 1.19-1.76) in autologous HSCT. Based on distinct patterns of healthcare utilization following HSCT, we identified factors associated with higher resource utilization and greater healthcare related expenditures. Earlier identification of high-cost and high-need HSCT long-term survivors could pave the way for clinicians to offer more continuous engagement in survivorship care delivery.

Immunosuppressive Drugs Alter α1-Antitrypsin Production in Hepatocytes: Implications for Epithelial Gap Repair.

Immunosuppressive drugs are an inherent component of hematopoietic stem cell transplantation (HSCT) for the prevention of acute graft-versus-host disease (GVHD). Circulating α1-antitrypsin (AAT), a serine-protease inhibitor produced predominantly by hepatocytes that rises during acute phase responses, is lost in patient's stool due to gastrointestinal GVHD, and its augmentation has been found to attenuate GVHD. Here we explored the effect of immunosuppressive drugs on hepatocyte production of AAT and intestinal epithelial gap repair. The effect of commonly used immunosuppressants on AAT production was examined in vitro using HepG2 cells and primary mouse hepatocytes, and their impact on human intestinal epithelial cell line gap repair was evaluated. Sera from 12 allogeneic HSCT recipients, obtained at 14 days post-transplantation, predating the diagnosis of GVHD (n=6), were examined for reepithelialization, with added clinical-grade AAT. Rapamycin compromised AAT production under inflammatory conditions. Mycophenolate mofetil and cyclosporine A (CSA) inhibited reepithelialization; AAT minimized the effect of CSA. Patient sera displayed superior gap repair with exogenous AAT. Functional insufficiency in circulating AAT may be the result of drug toxicities leading to ineffective gut reepithelization and compromised gut lining. Taken together, our data strengthen the rationale for incorporating AAT augmentation therapy into immunosuppressive treatment protocols.

Dissociationsof oral foci of infections with infectious complications and survival after haematopoietic stem cell transplantation.

IntroductionHaematopoietic stem cell transplantation (HSCT) recipients are at increased risk for severe infections. This study examined the associations of common oral infections with survival and infectious complications in HSCT recipients.Materials and methodsAll autologous and allogeneic HSCT recipients transplanted in the University Hospital of Basel, Switzerland, between 2008 and 2016 and referred to oral infection control pre-HSCT were included in this retrospective case-control study. All patients had a clinical and a panoramic radiological dental examination taken immediately prior to HSCT. Presence of acute or chronic oral foci of infections, decayed, missing or filled tooth index (DMFT) and radiological attachment loss (RAL) were examined. Survival and infections of the subjects were followed up for 6 months post-HSCT.ResultsAltogether 341 allogeneic and 125 autologous HSCT recipients were included in the study. Within 6 months post-HSCT, 47 (14%) of the allogeneic and 4 (3%) of the autologous recipients died. Oral foci of infections (acute or chronic), DMFT or periodontitis pre-HSCT were not associated with survival 6 months post-HSCT. Oral foci of infections were also not associated with hospital treated infectious diseases or blood culture positive bacteremia during the 6 month follow-up period. Untreated oral foci of infections were not associated with survival or severe infectious complications within 6 months post-HSCT.ConclusionThe results of this study suggest that radical dental interventions to chronic oral infections could be postponed until post-HSCT.

Impact of Amotosalen/UVA Pathogen Inactivated Platelet Components on Outcomes after Allogeneic Hematopoetic Stem Cell Transplantation: A Single Center Analysis

Background: Platelet component (PC) transfusion is required for allogeneic hematopoietic stem cell transplantation (HCT) recipients. Contamination with infectious pathogens (bacteria, viruses, or protozoa) and T-cells is a risk factor for transfusion-transmitted infection (TTI) and transfusion associated graft-versus-host disease (TA-GVHD). Pathogen inactivation (PI) treatment of PC with amotosalen-UVA (PI-PC, INTERCEPT Blood System, Cerus Corp) in platelet additive solution (PAS) without bacterial screening, gamma irradiation, CMV serology, and with 7-day storage has been the standard of care in Switzerland since 2011 to manage risk of TTI and TA-GVHD. PI-PC have replaced conventional PC (C-PC) prepared in PAS with gamma irradiation and 5 day storage. We previously reported platelet usage in two consecutive five year periods at the University Hospital of Basel. Mean PI-PC dose was higher (3.0 vs. 2.8 x 1011, p=0.001) and mean storage duration longer (4.2 vs. 3.4 days: p=0.001) than with C-PC. PC expiration wastage was reduced with 7-day PI-PC storage vs. 5-day storage (1.5% vs. 8.7%). For HCT recipients, days of PC support; PC use per patient; and RBC use per patient were similar, despite 24.3% lower corrected count increments (CCI) with PI-PC. Now, we report the impact of these observations on treatment related mortality (TRM) and overall survival (OS) 100 days after HCT. Patients and Methods: A two-period retrospective cohort study was conducted to evaluate PI-PC impact on outcomes of consecutive first allogeneic HCT recipients from January 2006 to December 2010 (Period 1, P1), when gamma-irradiated apheresis C-PC were used, and Period 2 (P2) from January 2011 to December 2017, when apheresis and whole blood-derived PI-PC were used. The review utilized 100-day OS and 100-day TRM to determine the impact of PI-PC on HCT outcomes. Descriptive statistics were used for continuous variables and log-rank analysis for survival outcomes. Univariate analysis was performed using Pearson χ2 statistics. Multivariate Cox regression modelling analyses included: PC period (P1, P2), donor match (HLA identical/twin, matched related, matched unrelated), disease state (early, intermediate, late), and conditioning regimen (reduced intensity, myeloablative) with TRM as the outcome. This was an IRB approved single-center analysis. Results: In P1 and P2, 256 and 557 consecutive first-time allogeneic HCT recipients were included, respectively. By univariate analysis, the distribution of European Group for Bone Marrow Transplantation (EBMT) risk scores (grouped 0-2, 3-4, 5-7) and mean patient age were higher during P2 (p = 0.001 and p &lt;0.001, respectively). Primary disease status (p = 0.039); stem cell source (p &lt;0.001); GVHD prophylaxis with ATG (p &lt;0.001); total body irradiation (p &lt;0.001); and conditioning regimen (p &lt;0.001) were different between P1 and P2. Donor match (p=0.084) and disease status (p = 0.628) were similar in P1 and P2. TRM at day 100 post HCT was significantly less (31/557, 5.5%) for PI-PC recipients in P2 vs. C-PC recipients in P1 (37/256, 14.5%, p&lt;0.001). Overall proportion of survivors at day 100 post HCT was significantly greater for PI-PC recipients (507/557, 91.0 %) compared to C-PC recipients (209/256, 81.6%, p &lt;0.001). By multivariate Cox regression analysis, P2 with PI-PC component support was associated with improved TRM (p = 0.001; adjusted hazard ratio 0.433; 95% confidence interval: 0.262, 0.716). Donor match (p = 0.019), disease state (p = 0.022), and myeloablative conditioning (p = 0.034) were associated with significantly poorer TRM (Table). Stem cell source was not significant (p=0.157) in the model. Hemorrhage was reported as cause of death in 1/50 (2.0%) patients during P2 with PI-PC and 4/47 (8.5%) patients during P1 with C-PCs. Conclusions: Universal implementation of PI-PC in routine with extended storage to 7 days in P2 was associated with reduced TRM and better overall survival 100 days post HCT, despite transplantation of older patients with higher EBMT risk scores. Multivariate analysis revealed an adjusted hazard ratio of 0.433 (95% C.I. 0.262, 0.716) for TRM by 100 days, suggesting better outcomes in P2. This retrospective analysis at a single site indicated that PI-PC treated with amotosalen /UVA stored up to 7 days did not have a negative impact on TRM and OS in HCT recipients, and was an integral part of improving clinical outcomes at our institution. . Table. Disclosures Heim: Novartis: Research Funding. Irsch:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.

Latent Tuberculosis in Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Strategies to Prevent Disease Activation in an Endemic Population

Introduction Latent tuberculosis infection (LTBI) affects one third of the world population. It is well known that patients with immunodeficiency are at a higher risk of developing active tuberculosis (ATBI). Hematopoietic stem cell transplant (HSCT) recipients have an incidence of ATBI 10 to 40 times greater when compared to the general population, this being related to a higher morbidity and mortality. The aim of this study was to determine the prevalence of LTBI and incidence of ATBI after transplant in recipients and donors of HSCT living in an endemic region. Methods Retrospective single-center study that included all HSCT recipients and donors treated and followed at our Institution between February 2000 and June 2018. LTBI and ATBI were categorized according to WHO definitions. Results A total of 411 patients were included: 125 allogeneic HSCT (allo-HSCT) recipients, 167 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Median age of the group was 34 years (range 11-70) and 59.9% were male (n=246). Baseline diagnoses that led to HSCT were: acute leukemia in 30.9% (n=127), lymphoma in 17.3% (n=71), and monoclonal gammopathy (MG) in 10.7% (n=44) (Figure 1). Allo-HSCT donors were matched related donors (MRD) in 84.8% (n=106), matched unrelated donors (MUD) in 3.2% (n=4), haploidentical in 10.4% (n=13), and umbilical cord in 1.6% (n=2). The source of HSCT was peripheral blood (PB) in 175 patients (59.9%), bone marrow (BM) in 50 patients (17.1%), primed-BM in 65 patients (22.3%), and umbilical cord in 2 patients (0.7%). All patients were evaluated pre-HSCT with tuberculin skin test (TST) and thoracic imaging. LTBI was diagnosed in 109 patients (26.5%): 21%, 20%, and 41.2% of patients were auto-HSCT recipients, allo-HSCT recipients, and allo-donors; respectively. One-hundred and seven patients had a positive TST and two patients presented findings suggestive of LTBI on chest X-ray. Seventy-eight percent of LTBI-HSCT recipients were further evaluated with chest CT (n=29), sputum (n=26), gastric fluid (n=15), and/or urine (n=25) cultures to rule out ATBI according to treating physician's criteria. In contrast, only 42.9% (n=21) of donors were further evaluated with chest CT (n=11), sputum (n=15), gastric fluid (n=2) and/or urine (n=12) cultures. All cultures were negative at follow-up. At LTBI diagnosis 80 patients (73.3%) initiated treatment with isoniazid (INH) 300mg daily for a minimum of 6 months. Treated HSCT recipients represented 91.7% and donors were 51%. Median days of therapy received before HSCT were 76 days (range 0-732) in HSCT recipients and 48 days (range 0-401) in donors. Distribution of cases according to the patient's state of residency, excluding Mexico City, revealed an increase prevalence of cases in the southern border of the country (Figure 2). ATBI incidence at 1 year of follow-up in the cohort was 0%. Only one patient developed a pulmonary mycobacterial-related infection; however, the species identified was M. chelonae. Conclusions To our knowledge, this is the first study that evaluates the prevalence of LTBI among HSCT recipients in a Latin American country where tuberculosis is endemic. We identified a prevalence of LTBI similar to what the WHO estimates; however, the presence of lower rates in recipients compared to donors in our population suggests a negative impact of depressed humoral immunity over the TST diagnostic yield. Interestingly, we do not report any ATBI cases post-transplant; pre-transplant diagnostic strategies, as well as length of treatment may be influencing factors for these outcomes. Collaborative working groups are required to stablish the best diagnostic and therapeutic approach in order to improve ATBI-attributable morbidity and mortality in this vulnerable HSCT-patient population. Disclosures Demichelis: AMGEN: Research Funding, Speakers Bureau; Abbvie: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Shire: Speakers Bureau.

Real World Outcomes of Letermovir Prophylaxis in Unselected High Risk CMV Seropositive Hematopoietic Stem Cell Transplant Recipients

Introduction: Cytomegalovirus (CMV) is a leading cause of morbidity following allogenenic hematopoietic stem cell transplant (HSCT). Letermovir (LTV), an orally available antiviral drug which inhibits the CMV-terminase complex, was recently approved for CMV prophylaxis in CMV-seropositive HSCT recipients due to its ability to significantly reduce the risk of clinically significant CMV infection and its favorable toxicity profile. In the pivotal phase 3 study, subgroup analysis suggested increased benefit of LTV in patients at higher risk for CMV infection (i.e. unrelated or haploidentical donor (HID) vs. matched related donor), however HID transplants represented only 16% of the study population1. Therefore, we conducted a retrospective analysis of CMV reactivation rates, before and after the initiation of routine LTV prophylaxis, to determine the real-world safety and efficacy of LTV in an unselected group of CMV-seropositive high risk HSCT recipients, including a large number of HID transplants. Methods: We conducted a retrospective review of 106 consecutive CMV-seropositive high risk allogeneic HSCT recipients between 2017 and 2019. We compared the incidence of CMV infection immediately prior to the initiation of routine LTV prophylaxis in high risk transplant recipients (pre-LTV) (n=41) to that occurring after the initiation of LTV prophylaxis (post-LTV) (n=63). HSCT recipients were considered high risk if they had received at least one of the following: transplant from a haploidentical donor, matched unrelated donor, umbilical cord blood donor source or received anti-thymocyte globulin. CMV infection was defined as the need for pre-emptive therapy or documented CMV disease. The cumulative incidence (CI) of CMV infection at 100 days and 180 days were calculated to accommodate death as a competing risk. We used the Wald test to compare the CI at 100 and 180 days between the two cohorts. Results: Baseline characteristics of the pre- and post-LTV cohorts were similar, with HID transplants making up the majority of HSCTs in both groups, 65% and 64% respectively. We found a significantly lower CI of CMV infection at both 100 and 180 days in the post-LTV cohort when compared to the pre-LTV cohort (19.4% vs. 68.3% and 27.6% vs. 71% respectively; p&lt;0.001) (Fig. 1). Despite lower CMV incidence following LTV prophylaxis, there was no significant difference in median time to CMV infection when compared to patients not receiving LTV prophylaxis (median [range] 40 [10, 243] vs. 36 [10, 180] days, p=0.72). The CI of CMV disease was 1.6% in the post-LTV cohort vs. 7.3% in the pre-LTV cohort (p=0.186). No significant differences were observed in any other outcome variable including overall survival, non-relapse mortality, relapse, acute graft-versus-host disease (GVHD) or time to neutrophil or platelet recovery. A preplanned subset analysis limited to HID transplant recipients (Fig. 2) again demonstrated a significant decrease in CMV infection in the post-LTV cohort at 100 and 180 days (27.9% vs. 80.8% and 34.6% vs. 84.6% respectively; p&lt;0.001). Conclusion: This single center analysis confirms the benefit of LTV prophylaxis in reducing the risk of clinically significant CMV infection in unselected high risk CMV-seropositive HSCT patients, including a substantial number of HID transplant recipients. We found no significant impact of LTV prophylaxis on any other transplant outcome including hematologic engraftment, GVHD, relapse or mortality. In contrast to the pivotal phase 3 study, we saw few CMV infections occurring past day 100 after discontinuation of LTV prophylaxis. Future planned analyses will include comparisons of antiviral usage and associated toxicities (i.e. cytopenias), overall treatment charges and hospitalization/resource utilization. Disclosures LaPorte: Merck: Speakers Bureau.

Psychological and Social Factors Are a Strong Predictor of Survival after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Independent of Disease Risk and Morbidity Score

Psychological and social factors are utilized as important part of the evaluation process for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The integration of such factors into the selection of suitable candidates and predicting survival post HSCT is still not widely incorporated in HSCT as it is the case in solid organ transplantation. To evaluate the impact of psycho social risks on post HSCT outcomes such as overall survival (OS), transplant related mortality (TRM), disease free survival (DFS), relapse and length of hospital stay, we prospectively conducted psycho social assessment on 556 consecutive allogeneic HSCT recipients who received their first transplant at our center between 2005 and 2017. The Transplant evaluation rating scale (TERS) has been previously published and was found to be psychometrically sound within the HSCT population(Hoodin, F. and Kalbfleisch, KR., Journal of Psychosomatic Research, 2003.) . TERS score was prospectively assessed by a psychologist prior to transplantation and patients were labeled as low/intermediate risk versus high risk based on their TERS score. All patients were transplanted in the outpatient setting with admission to the inpatient unit if clinically warranted. Five hundred and seven low/intermediate TERS patients and 49 high TERS were included in the analysis. Patients in the low/intermediate risk TERS group were more likely to have a higher disease risk index (17% versus 10%, p&amp;lt;0.001) and more likely to be transplanted in recent years (35% in 2015-207 versus 20% for high risk; p 0.005). Patients in high TERS group had longer, yet not significant, hospital stay during the first 180 days post allogeneic HSCT ( 21 vs 14 days for low/intermediate TERS p=0.22). Both groups had similar median age, sex, disease distribution, donor type, graft source, regimen intensity, HCT-CI score and KPS score. Median follow up for survivors was 66.7 months (14.0-184.4) for low/intermediate risk versus 94.8 months (15.9-182) for high TERS p&amp;lt;0.001. The survival estimates for low/intermediate and high TERS at 1 year were as follows (figure 1): OS (82% vs 63%, p=0.015), DFS (72% vs 57%), TRM (10% vs 16%) and relapse (18% vs 27%). The cumulative incidence of grade 2-4 GVHD and moderate-severe chronic GVHD were 38% and 30% for low/intermediate versus 31% and 27% for high TERS (P=NS). A multivariate analysis using cox models for OS, DFS, TRM, relapse , acute and chronic GVHD was performed using the following variables that were selected based on significance (p&amp;lt;0.05): age (&amp;lt;55 vs ≥55 years), gender, diagnosis, donor type (MRD, MUD, Haplo), source (BM, PBSC), regimen intensity, disease risk (low, intermediate, high), HCT-CI (0-2, ≥3), KPS (60-80, &amp;gt;80) and year of transplant ( 2005-2009, 2010-2014, 2015-2017). High TERS score predicted for worse OS (HR 2.04; 95% CI 1.32-3.17; p=0.002), worse DFS (HR 1.71, 95% CI 1.12-2.63, p0.014), a trend towards higher TRM (HR 1.62, 95% CI 0.86-3.05, p0.136) and relapse (HR 1.56, 95% CI 0.87-2.78, p=0.132) (table 1). In a subset analysis of patients with low/intermediate disease risk, multivariate analysis showed that high TERS predicted for worse OS (HR 1.97, 95% CI1.24-3.14, p=0.004), DFS (HR 1.74, 95% CI 1.10-2.75, p=0.018), trend for higher TRM (HR 1.91, 95% CI 0.98-3.72, p=0.057) and similar relapse rates. 1-year OS and DFS were significantly better for low/intermediate TERS 83% and 75% compared to high TERS 63% and 55% (p&amp;lt;0.05 for both) for patients with low/intermediate disease risk. Among a subset of patients with low HCT-CI ≤2 (n=317), patients in the high TERS group had higher TRM (25% vs 7%, p0.009) but no significant difference in OS, DFS, relapse and GVHD rates. In a multivariate analysis for HCT-CI 0-2 patients, high TERS was significant for higher TRM (HR 2.17, 95% CI 1.45-6.97, p=0.004). Our findings show that psycho social factors as measured by TERS score are a strong predictor of morbidity and mortality after allogeneic HSCT. This effect is independent of disease risk and morbidity prior to transplant. Psycho social factors should be included in patient selection and survival prediction models for transplant recipients. Figure 1: Survival and Relapse Estimates Based on TERS score Disclosures No relevant conflicts of interest to declare.

Anaerobic Antibiotics and the Risk of Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Background: The gut microbiota interacts extensively with the host immune system and thus may modify the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). During the post-transplant neutropenic period, the majority of allogeneic HSCT recipients receive empirical broad-spectrum antibiotics for febrile neutropenia. We hypothesized that receipt of an antibiotic regimen with an anaerobic spectrum of activity is associated with a higher risk of grade II-IV acute GVHD than receipt of a non-anaerobic antibiotic regimens. Methods: In this single-center retrospective cohort study, we evaluated associations between peri-transplant receipt of antibiotics with an anaerobic spectrum of activity and the risk and severity of GVHD among 877 adults who received an allogeneic HSCT between January 1, 2005 and December 31, 2016. We identified 609 patients who developed febrile neutropenia after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n=333) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, ceftazidime, or cefepime; n=276). Antibiotics received by patients between 7 days before and 28 days after allogeneic HSCT and GVHD diagnoses were verified via manual review of medication orders and provider notes in electronic medical records. Results: Receipt of anaerobic antibiotics was associated with an increased risks of grade II-IV acute GVHD (hazard ratio (HR): 1.41; 95% confidence interval (CI): 1.10-1.79; P=0.01) and acute GVHD mortality (HR: 1.87; 95% CI: 1.13, 3.11; P=0.02). This hazard was primarily associated with acute GVHD of the gut or liver (HR: 1.38; 95% CI: 1.06, 1.79; P=0.02). The association remained with even short (&lt;7 days) courses of anaerobic antibiotics. Anaerobic antibiotic exposure was not associated with acute skin GVHD (HR: 0.97; 95% CI: 0.69, 1.37; P=0.88), chronic GVHD diagnosis (HR: 0.93; 95% CI: 0.70, 1.23; P=0.43), or chronic GVHD mortality (HR: 0.89; 95% CI: 0.44, 1.81; P=0.76). Conclusions: Receipt of anaerobic antibiotics for febrile neutropenia post-HSCT is associated with an increased risks of acute GVHD of the gut or liver and acute GVHD mortality. Limiting use of antibiotics with an anaerobic spectrum of activity after allogeneic HSCT may reduce acute GVHD incidence and mortality. Disclosures Sung: Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding. Martin:Novartis Pharmaceuticals: Other: research support; Jazz Pharmaceuticals: Other: research support.

The Economic and Health Utilization Cost of Clinically Significant Cytomegalovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation

Introduction Understanding the economic impact of managing allogeneic hematopoietic stem cell transplant (HSCT) recipients with cytomegalovirus (CMV) is important for future planning within institutional transplant programs. CMV remains the most frequent viral infection following HSCT of which the clinical impact on transplant outcomes has been well described. However, much less is known about the impact of CMV on health resource utilisation, re-admissions and hospital costs. In addition to antiviral therapy, there are nursing, medical and pharmacy costs to consider. We therefore undertook a study to evaluate the clinical and economic burden of CMV infection following HSCT in a large Australian transplant centre operating under a universal health care system. Methods A retrospective single centre study at the Royal Melbourne Hospital, Melbourne, Australia was performed on all consecutive allogeneic HSCT recipients between January 2015 to December 2017. CMV pre-emptive monitoring using quantitative CMV plasma viral load was performed twice weekly from time of transplant to 100 days or longer in the presence of graft versus host disease. Clinically significant CMV (csCMV) was defined as patients receiving anti-CMV treatment, often with a plasma CMV viral load &amp;gt;400 IU/ml. Throughout the study period, the first line anti-CMV therapy was ganciclovir; either as oral valganciclovir for outpatient management in asymptomatic patients or IV ganciclovir as an inpatient for patients with concerns about oral absorption. Second-line therapy was IV foscarnet. Hospital costing data for the first and subsequent re-admissions for the first 12 months were obtained from the business intelligence unit. Financial year costing was available for FY2015/2016 to FY2017/2018. Ethics was approved by the Melbourne Health Human Ethics Review Committee (HREC 2017.368). Results A total of 255 patients underwent alloHSCT with a median age of 51 years (IQR 40-59) with the most common underlying diagnoses being AML (41%), ALL (11%) and MDS (11%) (Table 1). Thirty-one percent of transplants used myeloablative conditioning, 54% had unrelated donors and 3% had an umbilical cord source. Pre-transplant recipient CMV seropositivity was 62% (n=158), of whom 139 had detectable CMV viremia and 104 (40.8%) experienced clinically significant CMV (csCMV). The median duration of CMV treatment was 33 days (IQR 21-63). Re-admission to hospital within the first 12 months of HSCT occurred in 78.4%. There was a greater number of admissions observed in csCMV patients compared to no csCMV (median 3 vs 2 admissions, p=0.001) with the duration of admitted days within the first 12 months being significantly greater in csCMV patients compared to no csCMV (median 65 vs 36 days, p&amp;lt;0.00001). The mean total cost of treating patients with csCMV for the first 12 months compared to the total cost for patients not requiring CMV treatment was A$196,822 (US$147,616) and A$114503 (US $85,877) (p&amp;lt;0.0001), respectively. Therefore the crude attributable mean cost of treating csCMV was A$82,319 (US$61,739) per patient for the first 12 months of HSCT. The greatest significant contributory costs were from pharmacy A$17,807 (US$13,355), nursing A$16,944 (US$12,708) and medical A$5,898 (US$4,423). Conclusions The health care cost and resource utilisation of treating CMV infection following an allogeneic HSCT is substantial and places a heavy burden on limited health resources. In this study, patients experiencing csCMV had an increased number and longer total duration of admissions days compared to patients who did not require CMV treatment. Interventions aimed at reducing the burden of CMV in alloHSCT recipients are required. Disclosures Yong: Merck Ltd: Honoraria. Bajel:AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: travel funding. Ritchie:Sanofi: Honoraria; Novartis: Honoraria; Imago: Research Funding; Beigene: Research Funding; Takeda: Research Funding; BMS: Research Funding; Pfizer: Consultancy; Amgen: Consultancy, Honoraria, Research Funding. Slavin:Merck Ltd: Honoraria, Research Funding.

Incidence, risk factors, and outcome of blood stream infections during the first 100 days post-pediatric allogeneic and autologous hematopoietic stem cell transplantations.

Bloodstream infections (BSI) are a frequently observed complication after hematopoietic stem cell transplant (HSCT). Retrospective analysis of clinical and microbiological data during the first 100days from 302 consecutive pediatric patients who underwent HSCT for a malignant disease at our institute between January 2013 and June 2017. A total of 164 patients underwent autologous and 138 allogeneic HSCT. The overall incidence of BSI was 37% with 92% of infectious episodes occurring during the pre-engraftment phase. Gram-positive bacteria (GPB) accounted for 54.6% of the isolated pathogens, gram-negative bacteria (GNB) for 43.9%, and fungi for 1.4%. Coagulase-negative staphylococci and Escherichia coli were the most commonly isolated GPB and GNB, respectively. Forty-five percent of GNB were extended-spectrum beta-lactamase producers and 21% were multidrug-resistant organisms. Fluoroquinolone resistance was 92% and 68%, among GPB and GNB, respectively. Risk factors for BSI in univariate analysis were allogeneic HSCT, delayed time to engraftment more than 12days, previous BSI before HSCT, and alternative donor. In multivariate analysis, only HSCT type (allogeneic vs autologous P=.03) and previous BSI within 6months before HSCT (P=.016) were significant. Overall survival at day 100 was 98% and did not differ significantly between patients with and without BSI (P=.76). BSI is common in children undergoing HSCT for malignant diseases. Allogeneic HSCT recipients and previous BSI within 6months before HSCT are associated with increased risk of post-transplant BSI. With current supportive measures, BSI does not seem to confer an increased risk for 100-day mortality.

2695. Pneumocystis jirovecii Pneumonia in the Era of Effective Prophylaxis Following Hematopoietic Stem Cell Transplant

Background Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX prophylaxis is widely used.MethodsWe performed a single-center, retrospective case series of HSCT recipients from January 1, 2012 to December 31, 2018. Subjects had clinical symptoms and radiographic evidence for PJP along with at least one positive Pneumocystis test obtained from bronchoalveolar lavage (BAL) including direct fluorescence antibody (DFA), quantitative polymerase chain reaction (qPCR), cytology, and pathology.Results1111 subjects underwent HSCT; of whom, 25 (2.2%) met inclusion criteria and were treated for PJP. 6 were autologous and 19 were allogeneic HSCT recipients (1.23% and 3.05% of total autologous and allogeneic HSCT, respectively). All allogeneic HSCT recipients received in-vivo T-cell depletion. Median duration from autologous and allogeneic HSCT to PJP diagnosis were 138 days (range 20 to 348) and 346 days (range 41 to 771), respectively. PJP qPCR was positive in all samples tested (n = 20, range < 84 to 14900). DFA was positive in 6 (28%). Death from pneumonia occurred in 2 subjects; 11 (44%) required ICU stay, and 7 (27%) required intubation. At diagnosis, 3 subjects had relapse of underlying disease and 10 were on immunosuppression. 12 were on PJP prophylaxis (autologous HSCT n = 3), the most common of which was atovaquone (n = 5); only 2 subjects were on TMP-SMX. Cytomegalovirus (CMV) viremia was detected in 9 subjects (36%) prior to PJP diagnosis; 4 had pulmonary CMV coinfection. In total, 17 subjects (68%) had one of the above risk factors for PJP. Median total lymphocyte count and % lymphocytes were 5.1 × 103 cells/μL (range 1.4 to 38.5 × 103 cells/μL) and 9.6% (range 1.1 to 29.5%), respectively.ConclusionPJP is an uncommon (2.2% of the study population) complication of HSCT while receiving PJP prophylaxis and in the absence of disease relapse, CMV reactivation, or ongoing immunosuppression. Presentation is often delayed in this population; a high degree of clinical suspicion should prompt diagnostic evaluation using a combination of laboratory tests on BAL fluid. Disclosures All authors: No reported disclosures.

2672. Clostridioides difficile Infection Among Bone Marrow Transplant Recipients: Findings From a Single Institution

Background Clostridioides difficile infection (CDI) is increasingly common among hematopoietic stem cell transplantation (HSCT) recipients and efforts to define CDI risk have shown variable results. The primary objective of this study was to further characterize CDI incidence and risk factors in HSCT recipients.MethodsAll allogeneic and autologous HSCT recipients at Loyola University Chicago between January 2011 and May 2017 were retrospectively reviewed for development of CDI within 6 months prior to 2 years following HSCT. Collected data include comorbid conditions, statin or proton pump inhibitor (PPI), and antimicrobial use. HSCT baseline information was also obtained and include underlying malignancy, prior chemotherapy, graft type, conditioning regimen consisting of total body irradiation (TBI) use, and donor source (matched related or unrelated and umbilical cord blood). Among those with diagnosed CDI, data pertaining to CDI severity, treatment, and recurrence was collected. Logistic regression analyses were performed to estimate odds ratios for factors associated with development of CDI.ResultsSix hundred eighty-nine patients met our inclusion criteria. Of these, 367 (53%) underwent autologous HSCT and 322 (47%) allogeneic HSCT. Among all patients, 132 (19.1%) had CDI of which 26 (19.7%) had recurrence within 60 days. In univariable analysis, any type of leukemia was associated with increased odds of CDI compared with lymphoma (OR = 2.44, 95% CI: 1.49- 4.00, P < 0.01) as was allogeneic HSCT compared with autologous (OR = 2.51, 95% CI: 1.63–3.88, P < 0.01 for matched and OR = 3.96, 95% CI: 2.31–6.79, P < 0.01 for cord blood) and use of TBI (OR = 1.63, 95% CI: 1.10 – 2.40, P < 0.05). Exposure to any cephalosporin or intravenous vancomycin within 100 days of HSCT was associated with CDI (OR = 1.55, 95% CI: 1.03–2.32, P < 0.05 and OR = 1.75, 95% CI: 1.19–2.58, P < 0.01 respectively). No significant differences in the odds of developing CDI were identified by patient comorbidities, statin or PPI use.ConclusionIn our population there was a 19% incidence of CDI. Underlying leukemia, TBI exposure, and allogeneic HSCT appear to be risk factors for CDI and further research is needed to evaluate whether exposure to cephalosporin or vancomycin may be modifiable risk factors. Disclosures All authors: No reported disclosures.

Reproductive outcomes following a stem cell transplant for a haematological malignancy in female cancer survivors: a systematic review and meta-analysis.

The use of high-dose chemotherapy and radiotherapy combined with haematopoietic stem cell transplantation (HSCT) may negatively affect a woman's reproductive potential. Reproductive outcomes such as infertility are a major concern for women who undergo treatment for a haematological cancer diagnosis. This systematic review and meta-analysis explores reproductive outcomes following a haematological cancer requiring HSCT. Electronic databases were searched to identify studies that reported on reproductive outcomes after treatment for a haematological cancer diagnosis. Studies were included that reported on pregnancy and reproductive outcomes following HSCT for a haematological malignancy. The meta-analysis included 14 studies, collectively involving 744 female patients. The subgroup analysis showed an overall pooled estimated pregnancy rate, for autologous or allogeneic HSCT recipients, of 22.7% (n = 438). There were 25% (n = 240) of women who became pregnant after autologous HSCT compared with 22% (n = 198) who subsequently became pregnant following allogeneic HSCT. This meta-analysis reflects low pregnancy rates for cancer survivors desiring a family. However, live births are improving over time with new technology and novel therapies. Hence, female cancer patients should be offered timely discussions, counselling and education around fertility preservation options prior to starting treatment with gonadotoxic therapy.