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COVID-19 has significantly impacted the practice of hematopoietic cell transplantation (HCT) and likely affected outcomes of HCT recipients. Early reports document substantially higher case fatality rates for HCT recipients than seen in faced by the general population. Currently we do not have a clear picture of how much of this threat is present within the first year after HCT and how infection rates and outcomes vary with time after HCT. There are important because center-specific survival estimates for reporting purposes focus on 1-year post-HCT mortality. Transplantation centers have dramatically changed their practices in response to the pandemic. At many centers, quality assurance processes and procedures were disrupted, changes that likely affected team performance. Centers have been affected unevenly by the pandemic through time, location, and COVID-19 burdens. Assessment of center-specific survival depends on the ability to adjust for risk factors, such as COVID-19, that are outside center control using consistent methods so that team performance based on controllable risk factors can be ascertained. The Center for International Blood and Marrow Transplantation Research (CIBMTR) convened a working group for the 2020 Center Outcomes Forum to assess the impact of COVID-19 on both patient-specific risks and center-specific performance. This committee reviewed the factors at play and developed recommendations for a process to determine whether adjustments in the methodology to assess center-specific performance are needed.

Community respiratory viral infections (CRVIs) are associated with pulmonary function impairment, alloimmune lung syndromes and inferior survival in human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplant (HCT) recipients. Although the incidence of viral infections in HLA-haploidentical HCT recipients who receive post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is reportedly increased, there are insufficient data describing the incidence of CRVIs and the impact of donor source and PTCy on transplant outcomes. Analysing patients receiving their first HCT between 2012 and 2017 for acute myeloid leukaemia, acute lymphoblastic leukaemia and myelodysplastic syndromes, we describe comparative outcomes between matched sibling transplants receiving either calcineurin-based GVHD prophylaxis (SibCNI, N=1605) or PTCy (SibCy, N=403), and related haploidentical transplants receiving PTCy (HaploCy, N=757). The incidence of CRVIs was higher for patients receiving PTCy, regardless of donor type. Patients in the HaploCy cohort who developed a CRVI by day +180 had both a higher risk of treatment-related mortality [hazard ratio (HR) 2⋅14, 99% confidence interval (CI) 1⋅13-4⋅07; P=0⋅002] and inferior 2-year overall survival (HR 1⋅65, 99% CI 1⋅11-2⋅43; P=0⋅001) compared to SibCNI with no CRVI. This finding justifies further research into long-term antiviral immune recovery, as well as development of preventive and treatment strategies to improve long-term outcomes in such patients.

The COVID-19 pandemic has resulted in the increased use of cryopreserved grafts for allogeneic hematopoietic cell transplantation (HCT). However, information about the effect of cryopreservation on outcomes for patients receiving allogeneic donor grafts is limited. We evaluated outcomes of HCT recipients who received either fresh or cryopreserved allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) grafts reported to the Center for International Blood and Marrow Transplant Research. A total of 7397 patients were included in the analysis. Recipients of cryopreserved graft were divided into 3 cohorts based on graft source: HLA-matched related PBSC donors (n = 1051), matched unrelated PBSC donors (n = 678), and matched related or unrelated BM donors (n = 154). These patients were propensity score matched with 5514 patients who received fresh allografts. The primary endpoint was engraftment. Multivariate analyses showed no significant increased risk of delayed engraftment, relapse, nonrelapse mortality (NRM), or survival with cryopreservation of BM grafts. In contrast, cryopreservation of related donor PBSC grafts was associated with decreased platelet recovery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.68 to 0.78; P < .001) and an increased risk of grade II-IV (HR, 1.27; 95% CI, 1.09 to 1.48; P = .002) and grade III-IV (HR, 1.48; 95% CI, 1.19 to 1.84; P < .001) acute graft-versus-host disease. Cryopreservation of unrelated PBSC grafts was associated with delayed engraftment of neutrophils (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001) and platelets (HR, 0.61; 95% CI, 0.56 to 0.66; P < .001) as well as an increased risk of NRM (HR, 1.4; 95% CI, 1.18 to 1.66; P < .001) and relapse (HR, 1.32; 95% CI, 1.11 to 1.58; P = .002) and decreased progression-free survival (HR, 1.36; 95% CI, 1.20 to 1.55; P < .001) and overall survival (OS) (HR, 1.38; 95% CI, 1.22 to 1.58; P < .001). Reasons for cryopreservation were not routinely collected; however, in a subset of unrelated donor HCT recipients, the reason was typically a change in patient condition. Products cryopreserved for patient reasons were significantly associated with inferior OS in multivariate analysis (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). We conclude that cryopreservation is associated with slower engraftment of PBSC grafts, which may be associated with inferior transplantation outcomes in some patient populations. However, the small numbers in the cryopreserved BM cohort and the lack of information on the reason for cryopreservation in all patients suggests that these data should be interpreted with caution, particularly in the context of the risks associated with unexpected loss of a graft during the pandemic. Future analyses addressing outcomes when cryopreservation is universally applied are urgently required.

Peripheral blood stem cells (PBSCs) have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells. Current National Marrow Donor Program policy recommends 5 days of daily filgrastim, followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers between 2006 and 2016. Of these 22,348 donors, 20,004 (89.5%) had collection on 1 day, and the other 2344 (9.5%) had collection over 2 days. Information on why donors underwent apheresis in 1 day or 2 days was not available. Donors who underwent apheresis in 1 day were more likely to be male (67% versus 46%; P 30, 30% versus 22%; P

Objective/background: Clinical predictors of delayed engraftment following autologous hematopoietic cell transplantation (AHCT) are poorly described in the literature. The purpose of this study was to identify pretransplant characteristics contributing to delayed engraftment (DE) following AHCT. Methods: A retrospective, single institution study of 1162 consecutive patients undergoing AHCT from January 1996 to August 2016 was studied for DE. DE was defined as platelet count ≤ 50,000/µl, hemoglobin ≤ 8 g/dL, or absolute neutrophil count ≤ 1000/mm3. Results: Of the 1162 AHCT recipients, 263 (22.6%) were identified as having DE at 30-days post-AHCT with 80.0% being solely due to delayed platelet engraftment. Patients with Non-Hodgkin lymphoma (NHL) represented 18% of the original cohort, but accounted for 45% of those with DE, whereas multiple myeloma patients represented 59% of the initial cohort, but only 29% of those that had DE. At 3 months post-AHCT, transfusion dependence (p = .0083) prior to AHCT, low-infused CD34+ cell dose

Background Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis. Methods Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC). Results Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1–43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%. Conclusions The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.

Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) are generally older and have more comorbidities. Therefore, identifying personalized treatment options for each patient early and accurately is essential. To address this, we developed a computational biology modeling (CBM) and digital drug simulation platform that relies on somatic gene mutations and gene CNVs found in malignant cells of individual patients. Drug treatment simulations based on unique patient-specific disease networks were used to generate treatment predictions. To evaluate the accuracy of the genomics-informed computational platform, we conducted a pilot prospective clinical study (NCT02435550) enrolling confirmed MDS and AML patients. Blinded to the empirically prescribed treatment regimen for each patient, genomic data from 50 evaluable patients were analyzed by CBM to predict patient-specific treatment responses. CBM accurately predicted treatment responses in 55 of 61 (90%) simulations, with 33 of 61 true positives, 22 of 61 true negatives, 3 of 61 false positives, and 3 of 61 false negatives, resulting in a sensitivity of 94%, a specificity of 88%, and an accuracy of 90%. Laboratory validation further confirmed the accuracy of CBM-predicted activated protein networks in 17 of 19 (89%) samples from 11 patients. Somatic mutations in the TET2, IDH1/2, ASXL1, and EZH2 genes were discovered to be highly informative of MDS response to hypomethylating agents. In sum, analyses of patient cancer genomics using the CBM platform can be used to predict precision treatment responses in MDS and AML patients.

Background Consensus definitions for the diagnosis of invasive fungal diseases (IFDs) were updated in 2020 to increase the certainty of IFD for inclusion in clinical trials, for instance by increasing biomarker cutoff limits to define positivity. To date, there is a paucity of data as to the impact of the revised definitions on clinical trials. Methods In this study, we sought to determine the impact of the new definitions on classifying invasive aspergillosis (IA), the most common invasive mold disease in immunocompromised patients. We reclassified 226 proven and probable IA cases plus 139 possible IFD cases in the Aspergillus Technology Consortium (AsTeC) and in an antifungal prophylaxis trial (BMT CTN 0101) using the new criteria. Results Fewer cases met the more stringent diagnostic 2020 criteria after applying the reclassification criteria to define probable IA. Of 188 evaluable probable cases, 41 (22%) were reclassified to 40 possible IA and 1 probable IFD. Reclassification to possible IFD occurred in 22% of hematologic malignancy (HM) patients, 29% of hematopoietic cell transplant (HCT) patients, and in no lung transplant (LT) patients. Date of diagnosis was established a median (range) of 3 (1–105) days later in 15% of probable IA cases using the new criteria. Applying the new definitions to the BMT CTN 0101 trial, the power to detect the same odds ratio decreased substantially. Conclusions The updated IA consensus definitions may impact future trial designs, especially for antifungal prophylaxis studies., Using more stringent consensus diagnostic definitions for Invasive Aspergillosis, more than 20% of cases in hematopoietic cell transplant and hematologic malignancies patients that met earlier definitions no longer meet diagnostic criteria. This has important implications for antifungal prevention trials.

BACKGROUND: Cytomegalovirus (CMV) is a complication of allogeneic haematopoietic cell transplantation (allo-HCT). ASP0113, a DNA-based vaccine, contains two plasmids encoding human CMV glycoprotein B and phosphoprotein 65 (pp65). We assessed ASP0113 in CMV-seropositive allo-HCT recipients. METHODS: In this phase 3, randomised, placebo-controlled study, CMV-seropositive allo-HCT recipients were randomly assigned (1:1) via interactive response technology to receive five injections of 1 mL of 5 mg/mL ASP0113 or placebo. The pharmacist and designated staff were unblinded. Masked syringes maintained the blind for patients and study personnel. Efficacy and safety analyses included patients who received ≥1 dose of ASP0113/placebo. The primary efficacy endpoint was the proportion of allo-HCT recipients with composite all-cause mortality and adjudicated CMV end-organ disease (EOD) by 1 year post-transplant. ClinicalTrials.gov: NCT01877655 (not recruiting). FINDINGS: Patients were recruited between Sept 11, 2013 and Sept 21, 2016. Overall, 501 patients received ≥1 dose of ASP0113 (n = 246) or placebo (n = 255). The proportion of patients with composite all-cause mortality and adjudicated CMV EOD by 1 year post-transplant was 35.4% (n = 87) with ASP0113 and 30•2% (n = 77) with placebo (odds ratio 1.27; 95% confidence interval: 0.87 to 1.85; p = 0.205). Incidence of injection site-related treatment-emergent adverse events (TEAEs) was higher with ASP0113 than placebo. Overall incidence and severity of other TEAEs was similar between groups. T-cell response to pp65 increased over time and was greater with placebo than ASP0113 (p = 0.027). INTERPRETATION: ASP0113 did not reduce overall mortality or CMV EOD by 1 year post-transplant. Safety findings were similar between groups. FUNDING: Astellas Pharma Global Development, Inc . ispartof: ECLINICALMEDICINE vol:33 ispartof: location:England status: published

Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age ≥40 years who underwent alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR ≥90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR ≥90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR45 mL/min group. Compared with the eGFR ≥90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P.0001) and the eGFR45 mL/min group (HR, 3.09; P.0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR45 mL/min was associated with an increased overall mortality (HR, 1.63; P.0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.

Highlights • Transplant clinicians expect significant changes in the practice of hematopoietic cell transplantation over the next few years • There are considerable variations in practice predictions among adult and pediatric transplant clinicians • The degree of equipoise in the community about the relative efficacy of therapies being studied does not seem to affect accrual to current BMT CTN trials, Background Research priorities are best determined by the most pressing scientific questions, in the context of current knowledge. However, definitive research studies take time while real-world experience accumulates. Adoption of new practices before adequate comparison to current treatments threaten successful study conduct and may expose patients to what is ultimately learned to be inferior treatment. We conducted a survey to understand the Hematopoietic Cell Transplant (HCT) community's predictions about (a) future practice trends in the HCT field and (b) results of ongoing Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials to gauge how the HCT community views the treatments being studied. Method The survey was distributed between February and March 2019 to an electronic mailing list maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR) of HCT clinicians practicing in the United States. Results Of 986 clinicians surveyed, 315 responded (32%). They predicted an increase in the number of HCTs performed for malignant hematologic diseases and benign diseases such as sickle cell, autoimmune and genetic disorders. The majority (63%) predicted that matched related donors (MRD) will remain the preferred donor source for adult HCT recipients in 2023 but 21% predicted haploidentical (Haplo) and 17% predicted matched unrelated donors (MUD) would be the preferred donors. Most respondents (65%) predicted a decrease in the use of umbilical cord blood (UCB) as a graft source for HCT. Most respondents also predicted that calcineurin-based graft-versus-host disease (GVHD) prophylaxis would be replaced by post-transplant cyclophosphamide (PTCy) (55%), biomarker use would become standard practice to guide GVHD therapy (73%), and steroids would be combined with other agents for first line therapy for newly diagnosed acute and (53%) chronic GVHD (54%). In ongoing BMT CTN trials where outcomes are not yet known, 60% to 92% of respondents had an opinion about which arm they thought would be superior. However, not all respondents predicted the same outcome with a range of 44% to 88% choosing the same arm. There was not a clear relationship between the proportion predicting the same arm would win and accrual to the trial. Conclusion Survey respondents are optimistic about growth in the volume of transplant procedures, and they also expect significant changes in the practice of HCT over the next few years including wider adoption of PTCy GVHD prophylaxis, increased use of biomarkers to guide GVHD therapy, and decreased use of UCB HCT. The degree of equipoise in the community about the relative efficacy of therapies being studied did not seem to affect accrual to current BMT CTN trials but this is an area that needs further investigation.

The current COVID-19 pandemic, caused by SARS-CoV-2, has impacted many facets of hematopoietic cell transplantation (HCT) in both developed and developing countries. Realizing the challenges as a result of this pandemic affecting the daily practice of the HCT centers and the recognition of the variability in practice worldwide, the Worldwide Network for Blood and Marrow Transplantation (WBMT) and the Center for International Blood and Marrow Transplant Research's (CIBMTR) Health Services and International Studies Committee have jointly produced an expert opinion statement as a general guide to deal with certain aspects of HCT, including diagnostics for SARS-CoV-2 in HCT recipient, pre- and post-HCT management, donor issues, medical tourism, and facilities management. During these crucial times, which may last for months or years, the HCT community must reorganize to proceed with transplantation activity in those patients who urgently require it, albeit with extreme caution. This shared knowledge may be of value to the HCT community in the absence of high-quality evidence-based medicine. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD. ispartof: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION vol:25 issue:2 pages:362-368 ispartof: location:United States status: published

Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.

Limited data exist on characteristics of central nervous system viruses (CNS-V) in allogeneic hematopoietic stem cell transplant (HCT) recipients. Between 2007 and 2015, the Center for International Blood and Marrow Transplant Research (CIBMTR) received information on 27,532 patients undergoing HCT. Of these, centers reported 165 HCT recipients with CNS-V detected in cerebrospinal fluid within six months after HCT. CNS viruses predominantly included human herpes virus 6 (HHV-6) (73%), followed by Epstein-Barr Virus (10%), cytomegalovirus (3%), varicella zoster virus (3%), herpes simplex virus (3%) and Adenovirus (3%). Median time of viral detection in CNS was 31 days after HCT; and viral detection was earlier in patients with CNS HHV-6. Concurrent viremia occurred in 52% of patients. Cord blood transplant recipients (CBT) accounted for the majority (53%) of patients with CNS-V. Myeloablative conditioning (65%), use of fludarabine (63%), or use of anti-thymocyte globulin (61%) were also predominant. Overall survival from the time of detection of CNS-V was 50% at 6 months and 30% at 5 years. Infections were the leading cause of death (32%). In summary, CBT recipients predominated in the population with CNS-V. Outcomes after CNS-V were poor with significant mortality seen in the first 6 months.

Survivorship Care Plans (SCPs) may facilitate long-term care for cancer survivors, but their effectiveness has not been established in hematopoietic cell transplantation recipients. We evaluated the impact of individualized SCPs on patient-reported outcomes among transplant survivors. Adult (≥18 years at transplant) survivors who were 1-5 years post transplantation, proficient in English, and without relapse or secondary cancers were eligible for this multicenter randomized trial. SCPs were developed based on risk-factors and treatment exposures using patient data routinely submitted by transplant centers to the Center for International Blood and Marrow Transplant Research and published guidelines for long-term follow up of transplant survivors. Phone surveys assessing patient-reported outcomes were conducted at baseline and at 6 months. The primary end point was confidence in survivorship information, and secondary end points included cancer and treatment distress, knowledge of transplant exposures, health care utilization, and health-related quality of life. Of 495 patients enrolled, 458 completed a baseline survey and were randomized (care plan=231, standard care=227); 200 (87%) and 199 (88%) completed the 6-month assessments, respectively. Patients’ characteristics were similar in the two arms. Participants on the care plan arm reported significantly lower distress scores at 6 months and an increase in the Mental Component Summary quality of life score assessed by the Short Form 12 (SF-12) instrument. No effect was observed on the end point of confidence in survivorship information or other secondary outcomes. Provision of individualized SCPs generated using registry data was associated with reduced distress and improved mental domain of quality of life among 1-5 year hematopoietic cell transplantation survivors. Trial registered at clinicaltrials.gov 02200133.

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

Purpose: Allogeneic hematopoietic stem-cell transplantation (HSCT) is a curative treatment for many hematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T cells is a simple approach to rebuild immunity while limiting GvHD after haploidentical HSCT, but the optimal T-cell dose and impact on immune reconstitution remain unknown. Patients and Methods: We performed a multicenter phase I trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT. The primary aim was feasibility and safety with secondary aims of assessing the less frequently addressed issue of impact on immune reconstitution. Results: Nineteen patients with high-risk acute leukemia or myelodysplasia were enrolled. Engraftment occurred in 18 of 19 patients (95%). Pre-aDLI, 12 patients (63%) had bacteremia, nine of 17 at-risk patients (53%) reactivated CMV, and one developed acute GvHD. Sixteen patients received aDLI at dose levels 1 (103 T cells/kg, n = 4), 2 (104, n = 8), and 3 (105, n = 4). After aDLI, five patients developed clinically significant acute GvHD, and four of 14 at-risk patients (29%) reactivated CMV. T-cell recovery was significantly greater, and functional virus- and tumor-associated antigen-specific T cells were detectable earlier in patients receiving dose level 2 or 3 versus dose level 1/no aDLI. Alloanergization of donor cells expanded the CD4+ T-regulatory cell frequency within aDLI, which increased further in vivo without impeding expansion of virus- and tumor-associated antigen-specific T cells. Conclusions: These data demonstrate safety and a potential role for aDLI in contributing to immune reconstitution and expanding tolerogenic regulatory T cells in vivo after CD34-selected myeloablative haploidentical HSCT. Clin Cancer Res; 24(17); 4098–109. ©2018 AACR.

Significant advances in hematopoietic cell transplantation (HCT) have increased the long-term survivorship of its recipients, but because of unique complications arising from radiation and chemotherapy, recipients require lifelong follow-up. To evaluate current survivorship or long-term follow-up (LTFU) clinics specifically for HCT survivors and to evaluate the potential barriers in their establishment, the American Society for Blood and Marrow Transplantation (ASBMT) Practice Guidelines Committee electronically surveyed 200 HCT programs to gather quantitative and qualitative data about models of care. Among 77 programs (38.5%) that responded, 45% indicated presence of an LTFU clinic; however, LTFU care models varied with respect to services provided, specialist availability, type of patients served, and staffing. Among 55% of programs without an LTFU clinic, 100% agreed that allogeneic HCT survivors have unique needs separate from graft-versus-host disease and that complications could arise during the transition of care either from pediatric to adult settings or away from the HCT center. Lack of expertise, logistics, financial issues, and the observation that 84% of individual practitioners prefer to provide survivorship care were the identified obstacles to establishing new LTFU clinics. The ASBMT hopes that policymakers, HCT providers, and institutions will benefit from the results of this survey and recommends that delivering guidelines-driven screening and expert management of late effects is the goal of first-rate HCT survivorship care.

Acute graft-versus-host disease (aGVHD) contributes to poor outcomes and increased healthcare resource utilization (HRU) after allogeneic hematopoietic stem cell transplantation (HCT). However, HRU and the economic burden of aGVHD based on severity of the disease is not well characterized. Our study cohort comprised 290 adults who underwent allogeneic HCT between 2010 and 2018. Costs, HRU, and all-cause mortality in the 100-day and 365-day periods after HCT were compared between patients with aGVHD and those without aGVHD. The impact of aGVHD severity and gastrointestinal (GI) involvement on mortality, HRU, and economic burden was also evaluated. Medical costs and total hospital length of stay (LOS) were retrieved from administrative data that allocate costs to services based on departmental input for resource use and were adjusted to 2018 dollars. The Wilcoxon rank-sum test was used to compare the number of inpatient days and total costs. Multivariable linear regression was fitted on log-transformed costs. Compared with patients without aGVHD, those with aGVHD had a significantly greater median hospital LOS (28 days versus 22 days) and higher rates of intensive care unit (ICU) admission (13% versus 6%) and rehospitalization (59% versus 38%) during the first 100 days post-HCT. The presence of grade I-II aGVHD significantly prolonged the hospital LOS by a median of 3 days and increased the readmission rate by 18%, whereas grade III-IV aGVHD was associated with a nearly 30% increase in the readmission rate and a doubling of inpatient LOS, ICU admission rate, and mortality in the first 100 days post-HCT. Compared with the absence of aGVHD, lower GI involvement in aGVHD was also associated with increased risk of readmission (30%) and twice as many inpatient days, doubling the likelihood of ICU admission and mortality over the first 100 days. Similar findings were observed over days 101 to 365 post-HCT. The mean cost attributable to aGVHD regardless of grade was $60,923 in the first 100 days post-HCT. This cost varied by grade. The mean aGVHD- attributable costs were $18,071 for grade I, $36,115 for grade II and $120,929 for grade III/IV aGVHD and $114,668 for aGVHD involving the lower GI tract. In the 101- to 365-day period, the mean attributable aGVHD cost regardless of grade was $17,527. This cost also varied by grade. There were no additional aGVHD-attributable costs for grade I, but the mean aGVHD-attributable costs were $9743 for grade II, $62,220 for grade III/IV, and $55,724 for aGVHD with lower GI involvement compared with the controls without aGVHD. High-grade aGVHD and GI involvement in aGVHD, especially lower GI aGVHD, is associated with a considerably increased mortality and healthcare economic burden. Therefore, it is imperative that new therapeutic strategies be developed for this patient population.

One critical factor impeding successful management of invasive aspergillosis (IA) is the lack of reliable biomarkers to assess therapeutic response. We hypothesized that changes in certain host biomarkers reflect the nature of infection status and disease progression. Upon primary IA diagnosis, these disease status biomarkers can be monitored to track response to antifungal therapy and provide early markers that prognosticate likelihood of response. Herein, we analyzed serum levels of three prominent host disease status biomarkers C-reactive protein (CRP), haptoglobin (Hp), and annexin A1 (ANXA1) in IA patients during antifungal therapy. A total of 81 serial serum samples were collected at five or six different time points relative to IA diagnosis from 15 probable IA patients (10 acute leukemia [AL] and five hematopoietic stem cell transplantation [HSCT]). Of note, different biomarker profiles were observed in AL and HSCT patients, as not only levels of markers were significantly lower in HSCT patients but also more prominent interconnections among markers were observed in AL patients. Using a composite evaluation, patients were categorized as responders, nonresponders, and stable cases at last specimen. For AL responders, typical biomarker profiles were high initially but rapidly decreased for CRP and Hp post antifungal therapy, while low initial ANXA1 values were restored to normal levels after treatment. In contrast, CRP and Hp were persistently elevated whilst ANXA1 remained low throughout therapy in AL non-responders. As a pilot proof-of-concept study, our work demonstrates the great potential of using host biomarkers to monitor early therapeutic response in leukemia patients.

BACKGROUND Stress is a potent immunomodulator contributing to chronic conditions. Chronic graft-versus-host disease (cGVHD) is a life-threatening late effect of allogeneic hematopoietic cell transplantation associated with stress and exaggerated immune response that may be associated to lifestyle behaviors. OBJECTIVE The aim of this study is to explore associations among lifestyle behaviors, perceived stress, and inflammation of individuals with cGVHD. METHODS A secondary analysis from a prospective observational study of 24 adults (≥18 years) with cGVHD was conducted. Demographic, clinical, and symptom data were assessed using medical records and validated self-report measures; inflammatory markers were assessed using multiplex and enzyme-linked-immunosorbent assays from plasma. RESULTS Spiritual growth and total perceived stress were correlated (P < .001). Nutrition and C-reactive protein were negatively correlated (P = .02). Physical activity and cytokines (interleukin [IL]-2, IL-4, IL-5, IL-7, IL-10, IL-12, IL-13, IL-17, and granulocyte colony-stimulating factor) were associated (P < .05). Perceived stress and inflammatory markers were not associated. Individuals did not routinely engage in assessed health-promoting lifestyle behaviors. CONCLUSION Associations in this sample were noted among lifestyle behaviors, perceived stress, and inflammation. Given these promising findings, further research with a larger sample size is needed to test these associations. Activity, nutrition, stress management, and social support interventions may reduce stress and inflammation. Particularly, connecting with one's higher-self may reduce levels of perceived stress. Finding ways to engage survivors in healthy lifestyle behaviors should be explored. IMPLICATIONS FOR PRACTICE Information from this study allows nurses to be informed about the role of lifestyle behaviors on inflammation and stress to provide anticipatory guidance to HCT survivors regarding lifestyle choices that may mitigate inflammation and stress to promote positive health outcomes.

Background: The use of HCT to treat older (≥60 years) patients with hematological malignancies has markedly increased in recent years, however, the long-term effects of HCT on distress, psychosocial functioning, and HQOL in older HCT survivors is largely unknown. Though older HCT survivors have a higher risk of disease recurrence, they may have less access to resources and subsequently experience more pronounced late effects of disease and treatment. Confidence in Survivorship Information (CSI) in this specific age group has not been reported. Methods: We conducted a secondary analysis on a subgroup of patients enrolled in INSPIRE (NCT01602211) and PCORI-SCP (NCT02200133) clinical trials. Eligibility criteria for inclusion include HCT patients who were ≥ 60 years at time of transplant performed in 2003-2014, survived ≥ 1 year post-transplant with no evidence of disease relapse or secondary cancers. Patients were eligible for inclusion irrespective of transplant type (autologous or allogeneic), diagnosis, donor source or conditioning regimen. Primary endpoint was distress level in older HCT survivors; secondary endpoints included CSI and HQOL outcomes. We collected baseline distress level as measured by Cancer and Treatment Distress (CTXD) score, HQOL (measured by SF-12 Mental and Physical Component Summaries (PCS/MCS) and CSI (measured by a 15-item CSI questionnaire). Sociodemographic, disease and transplant factors were extracted from medical databases. Nonparametric (Wilcoxon rank sum/Kruskal-Wallis) test was conducted for comparing 2 or 3 groups. Spearman correlation and univariate linear regression model were used to evaluate associations between CTXD/CSI and PCS/MCS. Bonferroni correlation was used to adjust for multiple pairwise comparisons within age group. Results: A total of 567 patients satisfied the eligibility criteria and were included in this analysis. Median age at time of HCT was 69 years with 57% male; two-thirds were autologous HCT recipients. Table 1 details patient characteristics. The median CTXD score for older HCT survivors was 0.7 (range 0-2.7, SD 0.6) indicating low/insignificant level of distress post-HCT. 20-30% of HCT survivors reported moderate distress when asked about concerns regarding relapse risk, loss of energy and functional decline. Type of transplant (auto vs allo), age group ( 2 years) showed no apparent effect on reported distress level. CSI median score was 1.4 (range 0-2) which remains consistent with the score reported previously by the original trial including all age groups, indicating that older HCT survivors may have similar level of confidence in their survivorship information as their younger counterparts. Of note, close to 20% of the older HCT survivors reported poor CSI when asked about strategies for prevention and treatment of long-term effects of HCT and when asked about their confidence in availability of community resources to deal with long-term HCT complications. No statistically significant correlation was identified between CSI in older survivors and transplant type, time from HCT, or age group. HQOL outcomes indicated a median PCS of 48.2 (range 21.1 - 62.9) and a median MCS of 54.7 (range of 14.9 - 67.2). Interestingly, even though not reflected on the overall median CTXD and CSI scores for this cohort, a significant individual association between CTXD/CSI and PCS/MCS measures of HQOL was found (Figure 1). A subgroup analysis conducted on older alloHCT recipients confirmed the same findings of clinically insignificant distress level (mean CTXD ≤1.1) while having a similar level of CSI when compared to all age groups. Interestingly, time from HCT (≤2 years vs > 2 years) showed no significant effect on distress level reported by older alloHCT survivors, and cGVHD status did not correlate with CTXD or CSI scores nor with PCS/MCS in older alloHCT survivors. Conclusion: This is the largest study to date to investigate patient-reported distress, CSI and HQOL in older HCT survivors. Our data indicate that older HCT survivors have low levels of stress after HCT and had confidence in survivorship information in most aspects of their care. However, targeted interventions should focus on improving strategies for prevention, treatment and availability of community resources to deal with late effects of HCT; aspects reported as points of low CSI by older HCT survivors. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Devine: Be the Match: Current Employment; Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.

Background: Hematopoietic cell transplantation (HCT) survivors have a complex and multiphase recovery period. Health care delivery and psychosocial interventions for HCT survivors are challenging as many HCT recipients live great distances from the facility where they had their HCT. Therefore, identifying factors associated with a patient's capability to self-manage symptoms is an important focus of survivorship research. A patient's self-efficacy may be important for the successful management of major stressors associated with treatments and recovery. Here, we aimed to evaluate the impact of perceived self-efficacy on distress, quality of life (QoL), depression, and fatigue, and identify the factors associated with lower self-efficacy. Methods: This cross-sectional study analyzed baseline data from a randomized controlled internet based self-management intervention trial (INSPIRE, NCT01602211) in adult (age 18 and older) survivors 2-10 years post HCT. Patients with recurrence or subsequent malignancy requiring cancer treatment during the two years prior to enrollment, inability to read and understand English and lack of access to email and the Internet were excluded. Data included medical records and patient-reported outcomes (PROs) including Cancer and Treatment Distress (CTXD) with 6 subscales, Patient Health Questionnaire depression scale (PHQ-8), Short Form 12 Health Survey (SF-12) physical function (PCS) and mental function (MCS) scores, Brief Fatigue Inventory (BFI) and Health Self-Efficacy. Pearson correlations were used to test bivariate associations for self-efficacy with CTXD, SF-12, BFI, and PHQ8. General linear models were used to test the independent association for CTXD and SF-12 outcomes with self-efficacy, controlling for selected sociodemographic and treatment covariates. Tenability of statistical model assumptions were examined, and no remediation was necessary. Results: Total of 1078 HCT survivors were included in the analysis. Participants were 18 to 76 years (mean age 51), 53% male, and over 90% white and non-Hispanic. Only 16% reported living in a rural area. A majority received an autologous HCT (55%) and were less than 5 years from their first HCT (54%). Among the allogeneic HCT recipients, more than half (60%) had active chronic Graft-versus-Host (cGVHD) and nearly 40% were on active systemic treatment. The mean self-efficacy score was 3.01 (SD 0.49). Female gender (p=0.014), younger age at HCT, younger age at cGVHD presentation, moderate to severe currently active cGVHD (p=0.003) and household income less than $40,000 (p < 0.001) were associated with lower self-efficacy. In bivariate analyses, self-efficacy was negatively correlated with mean total CTXD (r -0.5, p In a regression model investigating the impact of self-efficacy on CTXD controlled for demographics and disease characteristics , lower self-efficacy was independently associated with higher CTXD (beta -0.232; 95% CI (-0.294, -0.169), p< 0.001) (Table 1). Moreover, there was a significant positive relationship between self-efficacy and both mental (beta 4.68; 95% CI (3.82, 5.54); p Conclusion: Our study demonstrates that lower levels of self-efficacy reported by HCT survivors was independently associated with higher levels of symptoms such as fatigue and depression, lower QoL, and more cancer -related distress. Furthermore, self-efficacy is more likely to be impaired in females, younger adults, those with lower incomes, and survivors with active cGVHD. These findings support the value of self-management interventions focused on improving self-efficacy as having the potential to improve multiple symptoms and QoL in HCT survivors. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Jim: RedHill Biopharma: Consultancy; Janssen Scientific Affairs: Consultancy; Merck: Consultancy; Kite pharma: Research Funding. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy.

Introduction: The adverse events associated with hematopoietic stem cell donation have been extensively studied. There is an increasing literature linking psychological factors including stress, anxiety and depression to higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. Here, we aimed to evaluate whether pre-donation health related quality of life (HRQoL) markers predict toxicity profile and stem cell yield following stem cell donation in healthy donors. Methods: The study population included adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) who were enrolled in Related Donor Safety Study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HR QoL was assessed using the Short-Form (SF-8) in RDSafe and SF-12 questionnaire in BMT CTN 0201 (higher score is better). Pain and toxicity were collected on study specific forms. The primary outcome was the incidence of skeletal pain on day 5 of G-CSF administration. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms at 1 month, 6 months and 1-year post-donation. Another secondary outcome included CD34+ per liter of blood processed (x10 6/L) on day 5 of G-CSF as a measure of collection yield. The association between pre-apheresis HRQOL measures and pain and acute toxicities was characterized using means and SDs and compared using the t-test. Association between HRQoL and cell yield was assessed using the Pearson correlation coefficient. RD and URD were analyzed separately. Results: URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more (44% vs 21%). More RDs were collected with lower volume procedures ( The mean pre-donation physical component summary (PCS) and mental component summary (MCS) score of RDs were 54.5 (SD 7.0) and 55.1 (SD 5.8), respectively . In the univariate analysis (table 1), pre-donation lower PCS score of RDs was associated with significantly more grade 2-4 pain at 1 month (p=0.0038) and 1-year post-donation (p=0.0099) (Table 1). In multivariable analysis (table 2), pre-donation PCS remained significantly associated with grade 2-4 pain 1-month post-donation (p=0.0098). More specifically, RDs with pre-donation PCS scores in the higher quartile were less likely to experience pain compared with donors with PCS scores in the lower quartile (OR 0.1; 95% CI 0.01-0.83; p=0.005). There was also a trend toward increased grade 2-4 pain at 1-year post-donation among RDs with lower PCS score (p=0.0176). Other outcomes such as pain at day 5 of G-CSF, other toxicities at day 5 of G-CSF, 1 month, 6 months and 1-year post-donation were not associated with pre-donation PCS score. Similarly, there was no significant association between RD pre-donation MCS score and collection-related symptoms at any time point. The mean pre-donation PCS and MCS scores of URDs were 56.2 (SD 4.7) and 54.5 (SD 5.5), respectively . In a univariate analysis, there was no association between PCS score or MCS score and donation associated pain and toxicities at any time point post-donation. Due to low event rates, multivariable analysis was not performed in the URD setting. Based on the multivariable regression analysis, there was no correlation between pre-apheresis HRQoL score (PCS or MSC) and PBSC collection yield in either the RD or URD setting. Conclusion: Our study demonstrates that pre-donation QoL markers are significantly associated with the toxicity profile after PBSC donation in the RD setting as adult RD with lower pre-donation physical QOL experience increased levels of pain after a PBSC collection procedure. There were no such associations found in URD in this small sample. Our findings may help clinicians to identify donors at higher risk of pain with donation, and lead to personalized information and interventions (e.g. increased analgesia) for specific donors. Future study with a larger sample is required to validate the results. Figure 1 Figure 1. Disclosures Farhadfar: Incyte: Consultancy. Stefanski: Novartis: Honoraria. Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.

Background: AlloHCT survivors generally report higher rates of cancer- and treatment-related distress compared to the general population, although data on cancer and treatment Distress (CTXD) and Confidence in Survivorship Information (CSI) in older alloHCT recipients are limited. We have reported that older HCT survivors have generally low levels of distress and intermediate-high level of CSI (Al-Mansour et al, abstract submitted to ASH 2021 meeting). In this study, we describe specific distress and CSI concerns reported by older alloHCT survivors and their association with other patient-reported outcomes and transplant-related factors. Methods: This cross-sectional retrospective secondary analysis used baseline data from two randomized controlled trials of survivorship interventions in alloHCT recipients enrolled in 18 US transplant centers (combined dataset from survivorship care plan trial [NCT00799461] and internet based self-management intervention trial [NCT01602211]). A total of 181 enrolled patients transplanted from 2003-2014 were ≥60 years of age at alloHCT and were alive and disease-free at ≥1-year post-transplant. All donor and graft types were included in this analysis. Distress was measured by CTXD scale, in which higher values indicate higher levels of distress. Survivorship confidence was based on the CSI questionnaire, in which higher values indicate greater confidence. Health-related quality of life (HQOL) was assessed with the SF-12, with high scores indicating better physical function (PCS) and mental function (MCS). Clinical and sociodemographic variables were summarized in descriptive statistics. Non-parametric test (Wilcoxon rank sum test / Kruskal-Wallis test) was conducted for comparing two or three groups for CTXD/CSI. Spearman correlation and univariate linear regression model were used to evaluate associations between CTXD/CSI and PCS/MCS. Bonferroni correlation was used to adjust for multiple pairwise comparisons within age group at transplant. Results: The median age of this older sample at alloHCT was 64 (range 60-81), with the largest proportions non-Hispanic (96%), White (97%), and males (57%). The majority received peripheral blood grafts (88%) from an unrelated donor (65%) for their first (96%) transplant. At the time of the survey, survivors were at a median of 3 years (range 1-9) from alloHCT. Mean CTXD overall score was 0.85 (standard deviation [SD] 0.44). Among CTXD items, highest distress was reported for "low energy" (mean 1.42, SD 0.97) followed by "feeling tired and worn out" (mean 1.32, SD 0.93) and "not being able to do what I used to do" (mean 1.28, SD 0.98), while the lowest distress was reported for "communication with medical people"(mean 0.32, SD 0.66) and "getting information when I need it" (mean 0.39, SD 0.70; Figure 1). Similarly, mean CSI overall score was 1.39 (SD 0.44) in this Among CSI items, information on "disease treated" (mean 1.79, SD 0.41) scored the highest in confidence level followed by "treatment received for transplant" (mean 1.75, SD 0.46); meanwhile, information on "community resources for long-term effects of disease" (mean 1.14, SD 0.72) followed by "strategies for treating long-term physical effects of your treatment" (mean 1.15, SD 0.71) scored the lowest in confidence level (Figure 2). There were negative correlations between CTXD and PCS/MCS (P2 years) showed no apparent effect on CTXD or CSI overall scores. Conclusion: Older alloHCT survivors report low level of cancer- and treatment-related distress and a relatively high level of CSI. Physical and mental function were associated with lower distress and increased CSI. Survivorship intervention needs in older alloHCT recipients include management of fatigue, education on long-term effects, and improving knowledge of and access to resources for long-term recovery and reintegration to society. The CTXD and CSI scales provide opportunities to evaluate and tailor interventions to the needs of older survivors with the potential to improve alloHCT survivorship care for older adults. Figure 1 Figure 1. Disclosures Hong: Adaptive Biotechnology: Other: Current employment of my spouse. Farhadfar: Incyte: Consultancy. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Devine: Sanofi: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment; Vor Bio: Research Funding; Tmunity: Current Employment, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Kiadis: Consultancy, Research Funding. Wingard: Merck: Consultancy; AlloVir: Consultancy; Celgene: Consultancy; Shire: Consultancy; Janssen: Consultancy; Cidara Therapeutics: Consultancy. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy.

The incidence of debilitating oral mucositis (OM) can be as high as 99% after myeloablative conditioning regimens preparing patients with hematologic malignancies for hematopoietic cell transplantation (HCT). Palifermin (KGF) is a recombinant human keratinocyte growth factor that reduces the incidence and duration of severe OM. The long-term safety of KGF has not been well established, however. In this long-term prospective matched-cohort study, patients who received KGF (cases) and underwent autologous or allogeneic HCT for hematologic malignancies between 2006 and 2013 were matched 1:1 to patients who did not receive KGF (controls). The primary outcome was overall survival (OS). Other outcomes were disease relapse, new malignancies, pancreatitis, renal failure requiring dialysis, pulmonary complications, cataract surgery, and acute and chronic graft-versus-host disease (GVHD). The analysis population comprised 2191 matched pairs with a wide range of diseases and donor types that received diverse conditioning and GVHD preventive regimens, representing contemporary practice patterns. The median duration of follow-up was 8 years (range, 1 to 12.5 years). In multivariate analyses, the probabilities of OS (relative risk [RR], 1.01; 95% confidence interval [CI], 0.91 to 1.12), relapse (RR, 1.06; 95% CI, 0.94 to 1.18), new malignancies (RR, 0.89; 95% CI, 0.67 to 1.18), and cataract surgery (RR, 1.05; 95% CI, 0.74 to 1.50) were not statistically significantly different between cases and controls. In univariate analyses, no increased risks were observed for renal failure requiring dialysis, pancreatitis, acute GVHD, chronic GVHD, interstitial pneumonitis/acute respiratory distress syndrome/idiopathic pneumonia syndrome, or bronchiolitis obliterans/cryptogenic organizing pneumonia/bronchiolitis obliterans organizing pneumonia among cases compared with controls. This long-term prospective safety cohort study demonstrates that the KGF group had no increased risk of overall mortality, relapse, new malignancies, or any other key outcome. The broad inclusion criteria allow the results to be generalized to contemporary practice for patients with a wide range of diseases and receiving a wide range of HCT conditioning regimens and graft sources from diverse donor types.

Relapsed acute myeloid leukemia (AML) is a significant challenge after allogeneic hematopoietic cell transplant (HCT). Multiparameter flow cytometry (MFC), conventional cytogenetics (CG), and fluorescence in situ hybridization (FISH) are routinely performed on bone marrow specimens prior to HCT to assess disease status. We questioned the extent by which pre-HCT evidence of minimal residual disease (MRD) detected by these standard assays, corresponded with post-HCT relapse. We conducted a single center, retrospective study of 166 AML patients who underwent HCT. Thirty-eight of one hundred sixty-six (23%) patients in complete remission (CR) or CR with incomplete count recovery (CRi) had MRD detectable by MFC, CG, or FISH. MRD was more frequently seen in patients with poor risk karyotype at diagnosis (P = 0.011). MRD-negative patients (MRDneg) had significantly longer overall survival (OS) and relapse-free survival than patients who were MRD positive (MRDpos) (P = 0.002 and 0.013, respectively). In patients with MRDpos prior to HCT, the presence of acute graft vs. host disease (GVHD) (grade ≥ 2) or chronic GVHD significantly improved progression free survival (PFS) (hazard ratio (HR) = 0.053 (95% confidence interval (CI): 0.01–0.279), P = 0.0005) and OS (HR = 0.211 (95% CI: 0.081–0.547), P = 0.0014).

Introduction: Cryopreservation of peripheral blood stem cell (PBSC) or bone marrow (BM) grafts is rarely performed, thus information about the effect of cryopreservation on graft characteristics and HCT outcomes is limited. Given the global pandemic leading to changing practices for donor graft collection and increasing utilization of cryopreservation, we evaluated the outcomes of HCT recipients who received either fresh or cryopreserved allogeneic BM or PBSC grafts. The primary endpoint was engraftment. Secondary endpoints were incidence of acute graft-vs.-host disease (aGVHD), relapse, transplant related mortality (TRM), disease free survival (DFS), and overall survival (OS). Methods: We included 7397 patients transplanted between 2013 and 2018. 1883 cryopreserved graft recipients were divided into three cohorts based on graft source and donor type: matched related (MRD) PBSC (n=1,051), matched unrelated (MUD) PBSC (n=678), and matched related or unrelated bone marrow donors (n=154). All patients received conventional calcineurin-based GVHD prophylaxis strategies. Patients who received cryopreserved grafts were matched with 5514 patients who received fresh adjusting for graft type (BM vs. PB), donor source (MRD vs. 8/8 MUD), Disease Risk Index (DRI, low risk vs. intermediate risk vs. high risk), recipient age (within 5-years) and propensity score (within 1 standard deviation from pooled sample). The propensity score was based on age, Karnofsky score, diagnosis, disease risk index, HCT-comorbidity index, and conditioning intensity. The level of statistical significance for the main analyses was p Results: Baseline characteristics for all cohorts are shown in Table 1. CD34+ doses reflect enumeration at infusion. In univariate analyses, rates of graft failure and neutrophil recovery at day 28 were similar for cryopreserved and fresh grafts for BM or related PBSC recipients but differed in cryopreserved vs. fresh MUD PBSC (5% vs 2%, p Conclusions: The retrospective nature of this analysis, and the fact that cryopreservation is likely to have been performed in recipients with a different (higher) risk profile compared to those receiving fresh products limits our ability to draw firm confusions. Despite these limitations, we conclude that cryopreservation in some patient populations may have a negative impact on engraftment and transplant outcomes. The decision to cryopreserve donor grafts, particularly PBSC grafts, should be carefully considered and highlights the need for further investigation of the effect of cryopreservation of allogeneic grafts where patient factors can be controlled for. Disclosures Farhadfar: CSL Behring: Research Funding; Incyte pharmaceutical: Other: Member of GVHD advisory forum. Frey:Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Syntax: Consultancy, Honoraria. Devine:Magenta Therapeutics: Consultancy. Shaw:Orca Bio: Consultancy. Wingard:Shire: Other: Personal Fees - serve on data monitoring committee for clinical trial; Ansun: Other: Personal Fees - serve on data monitoring committee for clinical trial; Merck: Other: Personal Fees - serve on data monitoring committee for clinical trial; Cidara: Other: Personal Fees - serve on data monitoring committee for clinical trial; ReViral: Other: Personal Fees - serve on data monitoring committee for clinical trial.

Introduction: Acute GVHD (aGVHD) contributes to poor outcomes and increased healthcare resource utilization (HRU) after allogeneic stem cell transplantation (allo-HCT). However, HRU and the economic burden of aGVHD based on severity of the disease and organ involvement is not well characterized. We examined the HRU, cost and mortality associated with aGVHD severity from initial hospitalization (index admission) up to 100 days post allo-HCT. Methods: Study cohort included 290 adult (≥ age 18) recipients of a first allo-HCT at the University of Florida between 1/2010 and 1/2019. The electronic medical records were reviewed for all patients who developed aGVHD as well as 116 patients without aGVHD who lived at least 1 month after HCT. Clinical measures that characterize the severity of aGVHD and extent of organ involvement were collected from electronic medical records. Medical costs and total hospital days were retrieved from administrative data that allocate costs to services based on departmental input for resource use and were adjusted to 2018 dollars. Wilcoxon rank sum test was used to compare number of inpatient days and total cost. Chi-squared test was used to compare ICU admission rate. Multivariable linear regression was fitted on log transformed cost. Results are shown as cost multipliers that represent ratios on original cost scale. Results: Of the 290 patients, 174 developed aGVHD within 100 days of allo-HCT. A higher proportion of patients with aGVHD had a Karnofsky performance status Development of aGVHD was associated with a significantly higher total (inpatient and outpatient) cost. The mean total cost for patients with and without aGVHD were $226,545 and $165,622, respectively (P Conclusion: HRU, cost, and clinical outcomes were associated with the severity of aGVHD. Development of higher grades of aGVHD and LGI aGVHD were associated with a poor clinical outcome and considerably increased healthcare economic burden. Given these clinical and economic risks it is imperative that new therapeutic strategies are developed for this patient population. Disclosures Farhadfar: Incyte pharmaceutical: Other: Member of GVHD advisory forum; CSL Behring: Research Funding. Leather:CSL Behring: Research Funding. Itzler:CSL Behring: Current Employment, Current equity holder in private company. Wingard:CSL Behring: Research Funding.

Introduction Absolute lymphocyte count (ALC) recovery following autologous stem cell transplant(ASCT) has been shown to be an important factor for overall and progression free survival. This is thought to be mediated by improved immune reconstitution resulting in decreased adverse events. Objectives Our primary aim was to investigate the role of ALC recovery at day 30 (D30) following ASCT in the overall survival(OS) and progression free survival(PFS) in patients treated for multiple myeloma(MM). Our secondary aim was to evaluate the correlation between infused CD3 content and ALC D30. Methods Two hundred forty-six patients were identified from our center's CIBMTR database who underwent ASCT between 2000-2010 for MM. Following manual chart review one hundred twenty-five met criteria for inclusion in analysis. ALC D30 was defined as the closest ALC to D30 post ASCT +/- 7 days. Patients who did not have D30 ALC data (n= 87) or underwent tandem ASCT (n=25) were excluded. Descriptive data is available in Table 1. The cohort was split into two groups with ALC ≥ 500 cells x10^6/cu mm or ALC Results ALC D30 failed to show an association with either PFS or OS in the univariable and multivariable analyses. The Median PFS time in ALC ≥500 group was 23.7 months (95%CI: 18.4 - 29.7) compared to 30.1 months (95% CI: 15.5 – 70.5) in the ALC Conclusions Our study failed to show an association between ALC D30 recovery and OS or PFS in patients with MM undergoing ASCT. Previously identified factors such as age also did not show an association with OS and PFS in our study. Data on induction regimens was not collected for this study and maintenance therapy was not administered or data was unavailable for a large portion of our dataset which may contribute to the discrepancy with previously reported studies. CD3+ dose of cells infused showed a weak but statistically significant correlation with ALC D30.

Background Chronic kidney disease (CKD) is a known risk factor for post-HCT mortality. Currently, HCT-CI assigns a score of 2 for moderate-severe renal dysfunction based on serum creatinine (Cr), though Cr is not ideal marker of renal function and can be influenced by several factors. The aim of this study is to examine whether utilization of incremental degrees of renal dysfunction based on eGFR improves the utility of HCT-CI to predict allogeneic HCT outcomes. Method Patients age ≥40 years receiving HCT for malignancies from 2008 to 2016 were included. Estimated glomerular filtration rate (eGFR), calculated using CKD-epidemiology collaboration method, was used to categorize patients into 4 groups: eGFR ≥ 90ml/min (n=7062), eGFR 60-90 (n=5264), eGFR 45-59 (n=897) and eGFR Results eGFR groups were similar on disease risk index, graft and donor source, but patients with eGFR≥90 were younger and received a myeloablative regimen more frequently. Patients with eGFR Conclusion These findings provide support that degree of renal dysfunction is independent predictor of OS and TRM after allogeneic HCT. In addition, the newly developed RA-HCT-CI is valid in predicting both TRM and OS and performs similarly to original HCT-CI.

BACKGROUND: Hematopoietic stem cell transplant (HCT) survivors are burdened by a high prevalence and early onset of chronic disease. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population. HCT survivors are susceptible to multiple complications and may result in chronic illness. Unfortunately, no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), specifically designed to provide guidance for making healthy food choices. The aims of this study were to evaluate diet quality and nutrient intake adequacy of HCT survivors. A secondary aim was to assess their willingness to take part in a future dietary intervention. METHODS: Dietary intake of adults, who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1-y post-transplantation, was assessed using the Block 2014 food frequency questionnaire and diet quality was estimated using the Healthy Eating Index-2015 (HEI-2015). Nutrient intake adequacies of the group were estimated by the Estimated Average Requirement (EAR) cut-point method. RESULTS: Survivors’ (n=90) HEI-2015 scores averaged 61.6±1.1. Adherence to a good quality diet was reported by only 10% of survivors. Intakes of vitamins A, C and D, as well as magnesium and calcium, suggested inadequacy. Fiber intake at 8.9 g per 1000 kcal/d fell below the Adequate Intake recommendation. “Change in taste” was associated with lower quality of diet (p=0.02). HCT survivors within 2 y post-transplant were more receptive to participation in a dietary intervention compared to survivors beyond 2 y (95% vs. 65%, p=0.0013). CONCLUSION: Adult HCT survivors reported less than optimal adherence to the 2015–2020 Dietary Guidelines for Americans and had numerous short-fall nutrient intakes. However, their willingness to participate in a dietary intervention was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care.

In the absence of prospective studies that examine the effect of conditioning regimen intensity after T-cell–replete haploidentical transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS), a retrospective cohort analysis was performed. Of the 1325 eligible patients (AML, n = 818; ALL, n = 286; and MDS, n = 221), 526 patients received a myeloablative regimen and 799 received a reduced-intensity regimen. Graft-versus-host disease prophylaxis was uniform with posttransplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate mofetil. The primary end point was disease-free survival. Cox regression models were built to study the effect of conditioning regimen intensity on transplant outcomes. For patients aged 18 to 54 years, disease-free survival was lower (hazard ratio [HR], 1.34; 42% vs 51%; P = .007) and relapse was higher (HR, 1.51; 44% vs 33%; P = .001) with a reduced-intensity regimen compared with a myeloablative regimen. Nonrelapse mortality did not differ according to regimen intensity. For patients aged 55 to 70 years, disease-free survival (HR, 0.97; 37% vs 43%; P = .83) and relapse (HR, 1.32; 42% vs 31%; P = .11) did not differ according to regimen intensity. Nonrelapse mortality was lower with reduced-intensity regimens (HR, 0.64; 20% vs 31%; P = .02). Myeloablative regimens are preferred for AML, ALL, and MDS; reduced-intensity regimens should be reserved for those unable to tolerate myeloablation.

Introduction. There is little information on the effect of donor body mass index (BMI) on mobilization response to Filgrastim (G-CSF), especially in the unrelated donor setting. Obesity has been associated with chronic low-grade inflammation due to chronic activation of the innate immune system. Obesity-induced pro-inflammatory cytokines can interfere with bone marrow SDF1/CXCR4 axis and promote mobilization of progenitor cells leading to persistent leukocytosis and an increase in number of circulating progenitor cells. Given a higher number of circulatory progenitor cells in obese individuals compared to non-obese, a reduced G-CSF dose in obese donors may elicit adequate response, thus reducing the adverse events associated with peripheral blood stem cell (PBSC) collection. The aim of this study is to evaluate the impact of donor BMI on G-CSF mobilized peripheral blood progenitor cell yield in healthy donors. This study also examines whether there is a G-CSF dose threshold above which there is a significant increase in skeletal pain and other acute toxicities from mobilization without an appreciable increase in progenitor cell yield. Methods. The primary outcome was examination of CD34+ per liter of blood processed (x106/L) on Day 5 of G-CSF administration as a measure of collection yield. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms (fatigue, nausea, anorexia, insomnia, dizziness) at 24 hours after first G-CSF dose, day 1 to 5 of G-CSF administration, 2 days and 1-week post collection. The population studied was domestic unrelated G-CSF mobilized PBSC donors reported to the NMDP/CIBMTR between 2006 and 2016. G-CSF dosing was based on the NMDP weight-based dosing schema rounded to the nearest vial content. Donors were divided into normal, overweight, obese, and morbidly obese categories based on BMI. Multivariate analysis of collection yields between cohorts were done using linear regression analysis. Stepwise variable selection was used to add variables to the model: BMI group and G-CSF dose was forced into the final model as the variables of interest. Pain and acute toxicities at each time point were described using frequencies and compared between groups using chi-squared test or Fisher's exact test after adjusting for donor and baseline characteristics. Results. Examination of 20, 884 PBSC donors mobilized by G-CSF revealed a significant increase in collection yield in obese and morbidly obese compared to normal and overweight donors. Median CD34+ per liter of blood processed (x106/L) on Day 5 of G-CSF was 29.6, 36.4, 40.8 and 42.9 in normal, overweight, obese and morbidly obese donors, respectively (p Figure 1 shows the time course and degree of toxicities in different BMI categories. Obese and morbidly obese were more likely to experience grade 2-4 pain and toxicities compared with normal or overweight in both the peri-collection and early post-donation recovery period but by one week after donation most toxicities abated and there was no difference. Donors with a higher BMI were more likely to experience grade 2 to 4 skeletal pain 24 hours post first G-CSF dose, 2 days post donation and at day 1 to 5 G-CSF administration. In addition, donors with higher BMI were more likely to have grade 2-4 toxicities (fatigue, anorexia, insomnia) at day 1 to 5 of G-CSF and 2 days after collection. However, within each BMI group, incremental increase in G-CSF dose was not associated with greater pain or other toxicities. Conclusions. Our data indicates a correlation between average daily G-CSF dose and CD34+ cell yield in normal and overweight donors. However, in obese and morbidly obese donors, there was no benefit in CD34+ yield with increasing average daily G-CSF dose above 780 mcg and 900 mcg respectively. Therefore, there appears to be a maximum effective G-CSF dose for mobilization in obese and morbidly obese donors where higher doses of G-CSF add no additional benefit and may result in additional complications. Download : Download high-res image (677KB) Download : Download full-size image Disclosures Pulsipher: Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria; Adaptive Biotech: Consultancy, Research Funding; CSL Behring: Consultancy.

Fatigue is one of the most prevalent and distressing complications among hematopoietic stem cell transplantation (HCT) survivors, negatively affecting physical, social, and emotional domains of quality of life. Chronic systemic inflammation has been linked to alterations in nervous system activity and initiation of distressing symptoms, such as fatigue. Damage to gut mucosa due to alteration in gut microbiota (GM) composition and microbial translocation has been shown to increase systemic proinflammatory cytokines. The aim of this study was to evaluate the relationship between fatigue and GM by measuring the differences in GM composition in HCT survivors with and without persistent fatigue. This cross-sectional study included 30 adults who underwent HCT for a hematologic disease and were at least 1 year post-HCT. Patients with chronic graft-versus-host disease were excluded. Fatigue severity was assessed by the Brief Fatigue Inventory (BFI). Based on the BFI score, patients were grouped into 2 categories: 0 to 3 (without fatigue) and ≥4 (with fatigue). The V1 to V3 region of the 16S rRNA gene from fecal specimens was sequenced using the Illumina MiSeq. Sequencing reads were processed, denoised, and replicated, chimeras were filtered, amplicon sequence variants (ASVs) were generated, and taxonomy was assigned using DADA2. Beta diversity analysis through principal coordinate analysis was generated using the Bray-Curtis dissimilarity matrix, and the difference was tested using linear model with generalized least squares in R. An alpha diversity analysis was performed using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differ between the 2 groups. Based on the BFI results, patients were categorized into 2 cohorts: with fatigue (n = 14) and without fatigue (n = 16). The 2 cohorts were similar in terms of demographics, disease, and transplant characteristics. Based on the GM analysis, there was a significant difference in GM composition (beta diversity) between the 2 cohorts (P = .001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (P =.002). LEfSe analysis identified 46 discriminative features (P.05; linear discriminant analysis score2) whose relative abundance varied significantly among individuals with fatigue and those without fatigue. Ten ASVs were associated with the patients with fatigue, and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and the Lachnospiraceae family (Fusicatenibacter and Coprococcus spp), which are known to have the ability to ferment complex plant carbohydrates. These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT, which may guide the development of new approaches to treating fatigue based on manipulation of the GM.

Tyrosine kinase inhibitors are known to cause pulmonary complications. We report a case of bosutinib related bilateral pleural effusions in a patient with chronic myeloid leukemia. Characteristics of the pleural fluid are presented. We also discuss other tyrosine kinase inhibitors induced pulmonary toxicities, including pulmonary hypertension and interstitial lung disease.

This secondary analysis of a large, multicenter Blood and Marrow Transplant Clinical Trials Network randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes, including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pretransplantation Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores of the Short-Form 36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (P

Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory Tcells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26× 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR). Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder Tcell proliferation. Immunosequencing of the Tcell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following invitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

Although melphalan at a dose of 140 mg/m(2) (MEL140) is an acceptable conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients, very few studies compared it to the most commonly used dose of 200 mg/m(2) (MEL200). A retrospective review of records of MM patients (2001-2010) identified 33 patients who received MEL140 and 96 patients who received MEL200. As expected, significantly higher percentage of patients in the MEL140 arm were65 years or had cardiac ejection fraction50%, had Karnofsky score80, or had creatinine2 at the time of ASCT (P≤.01). There were no significant differences in incidence of treatment related mortality and morbidity. At a median follow-up of 74 months from ASCT, there were no significant differences in relapse free survival (RFS) and overall survival (OS) between the two groups. Similar proportion had myeloma status improve to ≥VGPR at 3 months post-ASCT. Usage of post-ASCT maintenance was similar. In multivariate cox proportional hazards model, only disease status of ≥VGPR at the time of ASCT significantly improved RFS (P=.024), but not OS (P=.104). In conclusion, MM patients who received MEL140 had similar long-term outcomes to MEL200 patients despite their older age and co-morbidities.

Several studies have suggested an association of mannose-binding lectin (MBL) deficiency with infections. In this study, we investigated the association between MBL deficiency and invasive fungal disease (IFD) in hematologic malignancy patients receiving myelosuppressive chemotherapy or hematopoietic stem cell transplant. MBL levels were quantified at the start of treatment in 152 patients who were followed for 6 months and scored as developing IFD or not. Forty-five patients (29.6%) developed IFD, of which 21 (46.7% of IFD cases and 13.8% of patients) were proven or probable IFD. Fifty-nine (38.8%) had MBL levels

Mucormycosis outbreaks have been linked to contaminated linen. We performed fungal cultures on freshly-laundered linens at 15 transplant and cancer hospitals. At 33% of hospitals, the linens were visibly unclean. At 20%, Mucorales were recovered from >10% of linens. Studies are needed to understand the clinical significance of our findings.

e19501 Background: Management of acute leukemia is often complicated by acute venous thromboembolism (VTE) and bleeding. However, it is unknown which risk factors contribute to these VTE and bleeding events, how they impact survival, or whether they warrant VTE prophylaxis. Methods: A retrospective study was conducted at the University of Florida Health Shands Hospital System. The study included patients aged 18 or older with acute leukemia who received induction chemotherapy between January 2000 and December 2011. Bleeding was defined as clinically significant non-major bleeding and major bleeding per the International Society on Thrombosis and Haemostasis guidelines. VTE was defined as pulmonary embolism, deep vein thrombosis of the upper or lower extremities, or visceral vein thrombosis. Results: Of the 250 patients with acute leukemia, 65 had VTE, 60 had bleeding, and 152 had no significant VTE or bleeding. There were 27 patients with both VTE and bleeding. There were no significant differences in demographics or disease types between these three groups. There was a total of 77 VTE events and 72 bleeding events. We performed a logistic regression analysis in a mixed model to identify risk factors for VTE and bleeding, considering leukemia type, presence of infection, chemotherapy, number of comorbidities, VTE prophylaxis, and transplant as covariates. Presence of infection and number of comorbidities were significantly associated with VTE (p = 0.0094 and 0.0009, respectively). We did not find any significant risk factor associated with bleeding. Kaplan-Meier survival analysis showed a non-significant difference in survival between the non-VTE, non-bleed group and the VTE group (Logrank test, p = 0.52). In contrast, survival in the non-VTE, non-bleed group was significantly higher than the bleed group (Logrank test, p = 0.0006). The table demonstrates higher two-year survival in the non-VTE, non-bleed group (68.7%) compared to the VTE and bleed groups (54.4% and 30.3%, respectively). Conclusions: Acute leukemia patients without VTE or bleeding had significantly higher duration of survival than patients with bleeding. Patients with acute leukemia and presence of infection or multiple comorbidities may warrant greater consideration of VTE prophylaxis. [Table: see text]

Invasive fungal infections are an important problem in the management of both solid organ and hematopoietic stem cell transplant recipients. This chapter summarizes the evidence and recommendations for preventing invasive fungal infections in transplant recipients. A summary of recommendations are presented in Table 64.1.

Prevention of infection is important in the susceptible patients undergoing transplantation. Accurate diagnosis continues to be a challenge, and response to treatment is often suboptimal, mainly due to immune defects that cannot be corrected during the course of an infection episode. Antimicrobial drugs are the cornerstone for prevention of opportunistic and other routinely encountered infections in patients undergoing solid organ and hematopoietic stem cell allograft transplantation. However, there are many controversies associated with antimicrobial prophylaxis. In general, antimicrobial prophylaxis is beneficial during periods when the infection risk is highest including the early postoperative period in patients undergoing visceral allograft surgery and those with acute allograft rejection; in HSCT recipients with pre-engraftment neutropenia and those with graft-versus-host disease, to name a few. In a number of other situations, a clear benefit from such innervation is not certain. In this chapter, we present a comprehensive discussion on challenges and controversies associated with antimicrobial prophylaxis in HSCT and SOT recipients.