Adult Hematopoietic Cell Transplantation Research Articles

Transplant Physicians’ Attitudes on Candidacy for Allogeneic Hematopoietic Cell Transplantation (HCT) in Older Patients: The Need for a Standardized Geriatric Assessment (GA) Tool

<h3>Background</h3> Despite improvements in conditioning regimens and supportive care having expanded the curative potential of HCT, underutilization of HCT in older adults persists (Bhatt VR et al, BMT 2017). Therefore, we conducted a survey of transplant physicians (TP) to determine their perceptions of the impact of older age (≥60 years) on HCT candidacy and utilization of tools to gauge candidacy. <h3>Methods</h3> We conducted a 23-item, online cross-sectional survey of adult physicians recruited from the Center for International Blood and Marrow Transplant Research between May and July 2019. <h3>Results</h3> 175/770 (22.7%) TP completed the survey; majority of respondents were 41-60 years old, male, and practicing in a teaching hospital. Over 75% were at centers performing ≥50 HCT per year. When considering regimen intensity, most (96%, n=168) had an upper age limit (UAL) for using a myeloablative regimen (MAC), with only 29 physicians (17%) stating they would consider MAC for patients ≥70 years. In contrast, when considering a reduced intensity/non-myeloablative conditioning (RIC/NMA), 8%, (n=13), 54% (n=93), and 20% (n=35) stated that age 70, 75, and 80 years respectively would be the UAL to use this approach, with 18% (n=31) reporting no UAL. TP agreed that Karnofsky Performance Score (KPS) could exclude older pts for HCT, with 39.1% (n=66), 42.6% (n=72), and 11.4% (n=20) requiring KPS of ≥70, 80, and 90, respectively. The majority (n=92, 52.5%) indicated an HCT-comorbidity index threshold for exclusion, mostly ranging from ≥3 to ≥ 5. Almost all (89.7%) endorsed the need for a better health assessment of pre-HCT vulnerabilities to guide candidacy for pts ≥60 with varied assessments being utilized beyond KPS (Figure 1). However, the majority of centers rarely (33.1%) or never (45.7%) utilize a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates ≥60 yrs. The largest barriers to performing GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff (Figure 2). Approximately half (n=78, 45%) endorsed GA now routinely influences candidacy. <h3>Conclusions</h3> The vast majority of TP will consider RIC/NMA alloHCT for patients ≥70 years. However, there is heterogeneity in assessing candidacy. Incorporation of GA into a standardized and easily applied health assessment tool for risk stratification is an unmet need. The recently opened BMT CTN 1704 may aid in addressing this gap.

Rabbit Anti-Thymocyte Globulin (ATG) Exposure after Ex Vivo T-Cell Depleted Hematopoietic Cell Transplantation Is Highly Variable and Impacts Immune Reconstitution in Pediatric and Young Adult Patients

<h3>Background</h3> Rabbit anti-thymocyte globulin (rATG) is used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host-disease and graft failure. Its main and unpredictable toxicity includes poor immune reconstitution (IR) associated with higher mortality: patients who early reconstitute CD4+ have lower non-relapse mortality (NRM) and higher survival. Recently, a population pharmacokinetic (PK) pharmacodynamic rATG model described the optimal ATG exposure in various T-replete HCT settings. No data is however available in EX VIVO T-Cell Depleted (TCD) HCT. The goal of this study is to determine the optimal exposure of rATG in a pediatric and young adult patient EX VIVO TCD HCT setting, allowing early IR. <h3>Methods</h3> Pediatric and young adult patients receiving their first allogeneic EX VIVO TCD HCT at Memorial Sloan Kettering Cancer Center (2008–2018) were included. No restrictions were applied in terms of donor source, indication, conditioning, and age. Only patients receiving rATG (alone) or no ATG were included in analyses. We estimated exposure of rATG, before, after and total as area under the curve; (AUC) (mg*d/L) for all patients using an established PK model (Admiraal et al.,Lancet Hematology 2017). Outcomes of interest were CD4+ IR,defined as CD4+ levels >50/uL at two consecutive measures within 100 days, overall survival (OS), and NRM. We evaluated the association between ATG exposures and IR using a smoothed exposure to define optimal ATG exposure after HCT.Cox proportional hazard models, and multi-state competing risk models were used for analyses. <h3>Results</h3> 223 underwent a TCD HCT. 186 were included in the analysis as they received rATG (n=165) or no ATG (n=21).120(65%) had malignant and 66 (35%) had non-malignant indications for HCT. Median age was 10.5 (0.2–44) years. For those who received rATG, median rATG exposure after HCT was 34.2(range 0.622-104). A lower post AUC was associated with higher probability of IR (p<0.0001:Fig 1), increased OS(p=0.01), and lower NRM (p=0.01). The threshold for better IR and outcomes was found to be <20mg*d/L. Probability of CD4+ IR varied depending on the ATG exposure; No ATG vs.<20 vs. >20 (p<0.0001:Fig 2). There was a difference in NRM according to the ATG exposure;<20 vs. >20 (p=0.03:Fig 3), and in NRM according CD4 IR at day 100 (IR:CI 4+/- 4% vs. No IR; CI 30+/-10%;p <0.0001). <h3>Conclusions</h3> In patients who received EX VIVO TCD graft, rATG plays crucial role in probability of CD4+ IR. Patients who had rATG exposure <20 mg*d/L had highest IR, higher OS and lower NRM. These results emphasize the importance of individualizing ATG dosing to target to a low ATG exposure after HCT to improve early CD4+ reconstitution, decrease NRM, and increase survival chances.

Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Adult Hematopoietic Cell Transplant Recipients: A Single Center Study

<h3>Background</h3> Hematopoietic cell transplant (HCT) recipients are at high risk for Varicella zoster virus (VZV) reactivation. Shingrix, the adjuvanted recombinant zoster vaccine, is a new alternative to the live-attenuated VZV vaccine for immunocompromised individuals. Post-marketing data on its immunogenicity and safety in HCT is limited. <h3>Objectives</h3> To assess the safety and immunogenicity of Shingrix vaccine in HCT recipients. <h3>Methods</h3> Single center retrospective study of 134 consecutive adult allogenic and autologous HCT recipients who received the full series (two doses) of Shingrix vaccine. Primary study end points were safety and immunogenicity defined as either seroconversion in previously seronegative individuals or 4-fold increase from baseline VZV IgG titers in previously exposed patients. <h3>Results</h3> Among the 134 patients who completed vaccine series, 39 patients including 25 allogeneic and 14 autologous HCT recipients (Figure), had serological data available at baseline and after completion of vaccine series. The median age of patients at the time of HCT was 61 years (IQR, 53-67). The median time from HCT to first dose of Shingrix vaccine was 9 months (IQR, 7-14) for the entire cohort, but it was significantly shorter in autologous versus allogeneic HCT recipients: 7 (IQR, 6-8) vs. 12 (IQR, 9-16) months (P=0.003 by Mann Whitney test), respectively. Vaccine administration was very well tolerated, out of 134 patients only two (1.4%) had documented adverse events following Shingrix (and other vaccines co-administered), including injection site reaction after second dose and flu-like syndrome with fatigue and non-productive cough after the first dose (n=1 each). Both reactions occurred in autologous HCT recipients. The median time from the second Shingrix dose to post-vaccination VZV IgG titer assessment was 3.5 (IQR, 2-6) months. A total of 16 (41%) patients had documented humoral vaccine responses as measured by post vaccination VZV IgG levels including 8/14 (57%) autologous HCT recipients compared to 8/25 (32%) allogeneic HCT recipients (P=0.18 by Fisher's exact test). Among the 16 responders, the VZV IgG antibody concentration index increased from 179 (2.1-559) to 3,868 (2,232-4,000) (P<0.0001 by Wilcoxon matched-pairs signed rank test). Of interest, 100% of the patients who were seronegative prior to vaccination (n=8) seroconverted in response to Shingrix. <h3>Conclusions</h3> A 2-dose course of adjuvanted recombinant zoster vaccine was well tolerated among adult HCT recipients. Vaccine humoral responses occurred in less than half of the patients although vaccine seems to be more immunogenic following autologous HCT and among seronegative patients. Although Shingrix vaccine is currently only licensed for VZV seropositive patients, our data indicate that this recombinant vaccine may also be useful for primary VZV immunization. Larger studies are needed.

Functional Mobility in Pediatric and Young Adult Hematopoietic Cell Transplant Patients: A Comparison of the Functional Mobility Score (FMS) and the Karnofsky Performance Status Scale and Lansky Play Performance Scale

<h3>Introduction</h3> Hematopoietic cell transplants (HCT) are often associated with profound physical deconditioning and decreased functional mobility with resulting decreased participation in mobility and play. Accurately reporting a patients' functional mobility is paramount to identify impairments and provide appropriate intervention. The established standard for evaluating an HCT patient's level of function, based on age, is the Karnofsky Performance Status Scale and the Lansky Play Performance Scale; both report functional capacity and performance of activities of daily living. The functional mobility score (FMS) is a therapist-developed, objective outcome measure for pediatric and young adult HCT patients incorporated into the Transplant Energize Me Patient Outcome (TEMPO) quality improvement project. <h3>Objective</h3> The aim is to investigate the relationship between the FMS and the Karnofsky Scales and Lansky Scales, including the rating of functional status. <h3>Methods</h3> The FMS and Karnofsky Scale or Lansky Scale are completed at defined time points during HCT admission and follow-up for HCT. The FMS is a composite score of six functional skills, each scored on a 7-point ordinal scale, completed for patients who are ≥42 months old (Table 1). The cumulative score is converted to a percentage; a higher score represents greater independence with functional mobility and functional skills, similar to the Karnofsky and Lansky scales. This retrospective study investigates those scores completed pre-transplant. Data was analyzed using nonparametric statistics. <h3>Results</h3> 52 patients transplanted from 2016 to 2019 were included in analysis. The mean ± standard deviation for Karnofsky Scale or Lansky Scale scores at initial assessment were 95.8±6.3%, while the mean FMS score was 91.1±12.0%. There was a significant, but weak, positive correlation between the two measures (r=0.306, p=0.027) (Figure 1). <h3>Conclusion</h3> The FMS and Karnofsky or Lansky Scales show a weak relationship. Based on preliminary results, additional time point comparisons between the measures may provide further information about functional capacity of this population. Specifically, further investigation is needed to determine if FMS might be a more sensitive measure for capturing functional impairment then the Karnofsky or Lansky Scales.

Antipneumococcal Seroprotection Years After Vaccination in Allogeneic Hematopoietic Cell Transplant Recipients.

International guidelines recommend vaccinating allogeneic hematopoietic cell transplant (HCT) recipients at 3 months after transplant, giving 3 doses of pneumococcal conjugate vaccine (PCV) followed by either a dose of 23-valent pneumococcal polysaccharide vaccine (PSV23) or a fourth PCV dose in the case of graft-versus-host disease (GvHD). However, the long-term immunity after this regimen is unknown, and there is no recommendation from 24 months after transplant regarding boosts. Our objective was to assess the antipneumococcal antibody titers and seroprotection rates of allogeneic HCT recipients years after different schedules of vaccination. We assessed 100 adult HCT recipients a median of 9.3 years (range: 1.7-40) after transplant. All patients had received at least one dose of PCV and were assessed for antipneumococcal immunoglobulin G (IgG) antibody titers against the 7 serotypes shared by PCV7, PCV13, and PSV23. Sixty-six percent of the patients had been vaccinated according to the current guidelines. Considering an IgG titer ≥ 0.35 µg/mL as protective for each serotype, the seroprotection rate was 50% for 7/7 serotypes and 70% for 5/7 serotypes, with no differences between the different vaccination schedules. The lack of seroprotection was associated with a transplant performed not in complete remission or from a cord-blood unit, a relapse after transplant, or chronic GvHD at assessment. Because only half of the vaccinated patients had long-term protection, pending prospective studies defining the best boost program after the initial one, we recommend the assessment of specific IgG titers starting from 24 months to decide for further doses.

Inpatient Antibiotic Stewardship Interventions in the Adult Oncology and Hematopoietic Stem Cell Transplant Population: A Review of the Literature

Objective: To review the use of antibiotic stewardship interventions in the adult oncology and hematopoietic cell transplantation (HCT) populations. Data Sources: A literature search of PubMed was performed from inception to October 31, 2019. The general search terms used were oncology, cancer, hematologic malignancy, antimicrobial stewardship, antibiotic stewardship, febrile neutropenia, neutropenic fever, de-escalation, discontinuation, prophylaxis, practice guidelines, clinical pathway, rapid diagnostics, Filmarray, Verigene, MALDI-TOF, antibiotic allergy, and antimicrobial resistance. Study Selection and Data Extraction: Relevant English-language studies describing interventions supported by the Infectious Diseases Society of America guidelines on "Implementing an Antibiotic Stewardship Program" were included. Data Synthesis: Antibiotic stewardship publications in the oncology population have increased in recent years. Studies have described the impact of stewardship interventions, including preauthorization, prospective audit and feedback, implementation of clinical pathways, de-escalation of empirical antibiotics for febrile neutropenia (FN) prior to neutrophil recovery, allergy assessments, and use of rapid diagnostic testing. Many of these interventions have been shown to decrease antibiotic use without increased negative consequences, such as affecting length of stay or mortality. Relevance to Patient Care and Clinical Practice: This review synthesizes available evidence for implementing antibiotic stewardship interventions, particularly de-escalation of antibiotics for FN and implementation of clinical pathways for FN and sepsis, in oncology patients and HCT recipients. Summary tables highlight studies and specific research needs for clinicians. Conclusions: Immunocompromised populations, including oncology patients, have often been excluded from stewardship studies. Antibiotic stewardship is effective in reducing antibiotic consumption and improving outcomes in this patient population, although more quality data are needed.

Yoga for Cancer-Related Fatigue in Survivors of Hematopoietic Cell Transplantation: A Feasibility Study

ContextCancer-related fatigue (CRF) is one of the most common symptoms experienced by cancer patients after hematopoietic cell transplantation (HCT). Yoga is an approach with supportive evidence to improve CRF in different cancer populations, but to our knowledge, it has not been tested in an adult HCT population. ObjectivesThe aim of this study was to evaluate the feasibility of a yoga intervention offered to adult HCT survivors with moderate-to-severe CRF. MethodsThis feasibility study used a single-arm, pretest-posttest design. Adult HCT survivors were enrolled in a six-week restorative yoga intervention that consisted of a one-hour once-weekly class with twice-weekly home practice using a DVD. ResultsTwenty participants (13 women and seven men) enrolled in this study with a mean age of 51 years (SD = 12.5). The sample consisted of 19 allogeneic HCT survivors, seven of whom had a history of acute graft-vs.-host disease (GVHD), six with active, extensive chronic GVHD, and one autologous HCT survivor. The accrual acceptance rate was 23.2% (20/86 HCT survivors) and retention rate was 60% (12/20). Overall adherence was 45.4%. No adverse events were reported. ConclusionThe results of this study suggest that a restorative yoga intervention in adult HCT survivors is safe and feasible. The incidence of GVHD may have impacted adherence. Strategies to improve accrual acceptance, retention, and adherence are needed.

Transplant center characteristics and survival after allogeneic hematopoietic cell transplantation in adults.

Allogeneic hematopoietic cell transplantation (alloHCT) is a highly specialized procedure. We surveyed adult transplant centers in the United States (US) and then used data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) (2008–2010) to evaluate associations of center volume, infrastructure, and care delivery models with survival post alloHCT. Based on their 2010 alloHCT volume, centers were categorized as low-volume (≤40 alloHCTs; N=42 centers, 1,900 recipients) or high-volume (>40 alloHCTs; N=41 centers, 9,637 recipients). 100-day survival was 86% (95% CI, 85–87%) in high-volume compared to 83% (95% CI, 81–85%) in low-volume centers (difference 3%; P<0.001). One-year survival was 62% (95% CI, 61–63%) and 56% (95% CI, 54–58%), respectively (difference 6%; P < 0.001). Logistic regression analyses adjusted for patient and center characteristics; alloHCT at high-volume centers (odds ratio [OR] 1.32; P<0.001) and presence of a survivorship program dedicated to HCT recipients (OR 1.23; P=0.009) were associated with favorable 1-year survival compared to low-volume centers. Similar findings were observed in a CIBMTR validation cohort (2012–2014); high-volume centers had better 1-year survival (OR 1.24, P<0.001). Among US adult transplant centers, alloHCT at high-volume centers and at centers with survivorship programs is associated with higher 1-year survival.

Engaging hematopoietic cell transplantation patients and caregivers in the design of print and mobile application individualized survivorship care plan tools.

INSPIRE (INteractive Survivorship Program with Information and REsources) is an online health program that includes a mobile app, website, health action plan, and individualized survivorship care plans for adult hematopoietic cell transplant (HCT) survivors. The INSPIRE program integrates two previously effective randomized control trials that tested an internet-based program and patient-centered survivorship care plans for HCT survivors. Three focus groups were conducted with a total of 22 participants (20 patients, 2 caregivers/patient advocates) to explore patient and caregiver preferences and to optimize the patient-centered emphasis of INSPIRE. Adult (age > 18 years at the time of study entry) HCT recipients had to be at least 1-year post-HCT to participate; caregivers/patient advocates were also eligible. Participants had to be able to communicate in English, could have any diagnosis, transplant type, or donor source, and could have had multiple transplants. All patient participants received an allogeneic HCT; average time since HCT was 8 years (range 2-22 years). The majority of participants were female (77.3%). Overall, the tools were well received by participants in this study, particularly the personalized features of all the tools. Major themes included interest in having the ability to tailor features to individual needs, and an interest in tracking information over time. Engaging patients and caregivers is invaluable to optimize tools designed to improve HCT survivorship care. Print, online, and mobile-based tools, tailored to individual patients' treatment history and requisite follow-up care, can provide otherwise unavailable expertise and guidelines for care.

Soluble C5b-9 As a Prognostic Biomarker for Thrombotic Microangiopathy at the Onset of Graft-Versus-Host Disease

Schmidt: Kypha Inc: Employment, Equity Ownership. Lee:Incyte: Research Funding; Syndax: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Kadmon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; AstraZeneca: Research Funding.

Freesia Study Design: JNJ-53718678 in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

Background Although Respiratory Syncytial Virus (RSV) is a commonly recognized respiratory pathogen that can cause upper respiratory tract infections (URTI) and severe lower respiratory tract infections (LRTI) in infants and young children, it can also affect immunocompromised (IC) patients. Hematopoietic cell transplantation (HCT) recipients are at high risk for severe disease caused by RSV. The progression of RSV from URTI to LRTI can cause significant morbidity, often leading to hospitalization, intensive care unit admissions for supportive care and results in mortality in 2-5% of RSV infected HCT recipients. At some clinical centers oral or intravenous ribavirin, intravenous immunoglobulin or anti-RSV-enriched antibody preparations are used to treat RSV infection. However, there are currently no approved direct-acting antiviral agents indicated for the prevention or treatment of RSV infection in IC adult patients. A recently conducted trial evaluating another RSV fusion inhibitor in HCT recipients demonstrated strong trends toward clinical benefit among patients who were early in their disease course and were severely immunocompromised. JNJ-53718678 (JNJ-8678) is a fusion protein inhibitor that was well tolerated and showed antiviral activity in a Phase 1b study of RSV-infected infants, and was well tolerated and demonstrated antiviral efficacy in healthy adult volunteers in a human viral challenge study. FREESIA will evaluate the clinical outcomes, antiviral activity, safety, tolerability, pharmacokinetics (PK), and PK/pharmacodynamics (PD) of JNJ-8678 in HCT recipients with RSV URTI who are at the highest risk for progression to LRTI. Study Design and Methods This is a randomized, double-blind, placebo-controlled, multi-center study to evaluate JNJ-8678 in adult and adolescent HCT recipients with RSV URTI. In the adult cohort, a sample size of approximately 249 patients is targeted. (Figure 1). Adult and adolescent HSCT recipients will be enrolled if they present for medical care with an absolute lymphocyte count &lt;1,000 cells/μL, a PCR-based diagnosis of RSV infection, new onset of at least one respiratory symptom (nasal congestion, rhinorrhea, cough or pharyngitis) and/or worsening of one of these symptoms, if chronic due to an existing diagnosis, within 4 days prior to the anticipated start of dosing and no evidence of abnormalities consistent with LRTI on a chest X-ray. Eligible patients will be randomized 2:1 to receive orally either 500 mg JNJ-8678 once-daily (qd) or placebo qd for 21 days. The follow-up period will be 28 days in duration. The primary endpoint is the proportion of patients developing RSV LRTI, by external adjudication. Clinical course of RSV infection, antiviral activity, health-related quality of life, RSV viral sequencing and RSV viral kinetics will also be assessed. The PK/PD relationship of JNJ-8678 exposure with selected efficacy and safety parameters will be explored. Safety and tolerability, including AEs, laboratory assessments, ECGs, vital signs, and physical examination will be assessed. This study will begin recruitment globally in the northern hemisphere in November 2019. This study will clarify the role JNJ-8678 may play in the treatment of RSV in a broader IC population, potentially addressing a substantial unmet medical need. Disclosures Chemaly: Gilead: Research Funding; Gilead: Other: Personal fees; Chimerix: Research Funding; ReViral: Other: Personal fees; Oxford Immunotec: Other: Personal fees; Ansun: Other: Personal fees; Chimerix: Other: Personal fees; Oxford Immunotec: Research Funding; Merck: Research Funding; Ansun Pharmaceuticals: Research Funding; Janssen: Other: Personal fees; ADMA Biologics: Other: Personal fees; Merck: Other: Personal fees; Clinigen: Other: Personal fees; Ablynx: Other: Personal fees. Boeckh:Chimerix: Research Funding; GSK: Other: Personal fees; Merck: Research Funding; GSK: Research Funding; Clinigen: Other: Personal fees; Merck: Other: Personal fees. Weber:Janssen Pharmaceuticals: Employment; Johnson &amp; Johnson: Equity Ownership. Fleischhackl:Johnson &amp; Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Stevens:Johnson &amp; Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Michiels:Johnson &amp; Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Rivas:Janssen Pharmaceuticals: Employment; Johnson &amp; Johnson: Equity Ownership. Chien:Johnson &amp; Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment. Witek:Johnson &amp; Johnson: Equity Ownership; Janssen Pharmaceuticals: Employment.

Post-Transplant Work Status of Young Adult Survivors of Allogeneic Hematopoietic Cell Transplant: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Background: Return to full-time work after hematopoietic cell transplant (HCT) is an important indicator of health recovery and overall function of survivors. Because young adult (YA) HCT patients are at a critical personal and professional developmental phase at the time of their illness, they face unique challenges potentially impacting their ability to work post-HCT. We aimed to assess the post-HCT work status of YA patients undergoing allogeneic HCT and examine pre-HCT factors associated with their work status at the 1-year time-point post-HCT. Methods: Using data from the Center for International Blood and Marrow Transplant Research (CIBMTR), we studied YA (18-39 years of age at HCT) survivors (alive ≥1-year post-HCT) of allogeneic HCT performed between 2008 and 2015 for malignant or non-malignant conditions. All conditioning regimens, stem cell sources, and donor types were included. Work status [full-time (FT), part-time (PT), unemployed, medical disability] was assessed at 6-months, 1-, 2-, and 3-years post-HCT. We performed a multivariable logistic regression to study the pre-HCT patient and disease related [patient age at HCT, sex, race/ ethnicity, pre-HCT education, pre-HCT work status, disease diagnosis, Karnofsky/ Lansky performance score, hematopoietic cell transplant comorbidity index (HCT-CI), marital status], and HCT-related (year of transplant, stem cell source, donor type, conditioning regimen) factors associated with post-HCT work status at the 1-year time-point [dichotomized as employed (in FT/PT work) vs unemployed (unemployed, medical disability)]. Results: A total of 1,365 allogeneic HCT recipients met the selection criteria. Median age at HCT was 30.8 years (range 18-39; interquartile range 9.3). Forty-four percent were females; 89% received HCT for malignant diseases (myeloid diseases: 62%, lymphoid diseases: 35%) and the remainder for non-malignant diseases (severe aplastic anemia, inherited abnormalities of erythrocyte differentiation/ function, and disorders of the immune system). Forty three percent received total body irradiation (TBI) based myeloablative conditioning regimens. Median follow-up time from HCT was 60.6 months (range: 12-121). From 6-months to 3-years post-HCT, the percentage of survivors employed FT (18% to 51%) and PT (7% to 11%) increased, and unemployed (38% to 18%) and on medical disability (37% to 20%) decreased (Figure 1). Of patients in FT work pre-HCT, 50% were either unemployed or had medical disability status at the 1-year time-point (Figure 2). Of those unemployed pre-HCT, 19% were working at 1-year post-HCT. In the multivariable logistic regression, survivors' pre-HCT work status was significantly associated with the post-HCT work status at 1-year time-point. Compared to patients working FT pre-HCT, patients who were unemployed and on medical disability were significantly less likely to be employed at 1-year post-HCT [pre-HCT unemployment: odds ratio (OR) of FT/PT employment 0.30; 95% confidence interval (CI) 0.20-0.48; pre-HCT medical disability: OR 0.46; 95% CI 0.30-0.71]. Females (OR 0.51; 95% CI 0.37-0.69) and patients with an HCT-CI score of 2 (OR 0.61; 95% CI 0.39-0.95), and ≥3 (OR 0.53; 95% CI 0.36-0.76) also had a lower likelihood of employment. Compared to patients with high school or lower education, patients with graduate school level education had significantly higher likelihood of employment (OR 2.53; 95% CI 1.72-3.71). Compared to patients treated with total body irradiation (TBI) based myeloablative conditioning, significantly higher odds of employment were seen in chemotherapy-based myeloablative conditioning (OR 1.81; 95% CI 1.28-2.56) (Table). Conclusions: In YA HCT survivors, the full-time and part-time work rates steadily improved post-HCT. Nonetheless, nearly 40% were still either unemployed or on medical disability even at 3 years post-HCT. Although there were limitations of the study including lack of post-HCT time-dependent covariates for the analysis and direct patient report for work status, our study findings provide an insight into the factors impinging on YA survivors' ability of returning to work and points to a need for return to work interventions. Disclosures Shaw: Therakos: Other: Speaker Engagement.

Risks and Benefits of Bronchoscopy during the First 100 Days Following Allogeneic Hematopoietic Cell Transplantation

BACKGROUND Pulmonary infiltrates are common after allogeneic hematopoietic cell transplantation (HCT) and can have infectious or non-infectious etiologies. Fiberoptic Bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is frequently used to evaluate these patients. However, the diagnostic yield can be highly variable according to patient populations, and the impact on management is not well defined, especially in the era of modern antimicrobial therapies. The aim of this study was to investigate the diagnostic and therapeutic yield of FOB-BAL in adult patients with pulmonary infiltrates during the first 100 days following HCT. METHODS We retrospectively reviewed the medical records of adult HCT patients who underwent FOB-BAL during the first 100 days post HCT between January 2005 and December 2015 at Mayo Clinic, Rochester, MN. The interval from HCT to FOB was stratified into early (days 1-30) vs. late (days 31-100). The finding of progressively more hemorrhagic effluent and/or ≥ 20% hemosiderin-laden macrophages in BAL were considered diagnostic for diffuse alveolar hemorrhage (DAH). Univariate and multivariate logistic regression models were fit to identify clinical and transplant characteristics that may impact the diagnostic yield of FOB-BAL. RESULTS A total of 114 patients (median age 55 years), representing 12% of all HCT patients underwent FOB-BAL. Underlying diagnoses were AML in 36%, MDS in 16%, ALL in 16%, MPN in 12% , CLL in 7%, and other in 13%. Transplants were from matched related donor in 43%, matched unrelated donor in 40%, and other donor/matching status in 17%. FOB-BAL was performed during the early period in 61% and during the late period in 39% of patients. In the early period, FOB-BAL provided a specific diagnosis in 49% of patients (30% DAH and 19% infection). In the late period, FOB-BAL had a diagnostic yield of 55% (14% DAH and 36% infection) (Figure 1). The distribution of bacterial and viral infections identified via BAL were similar during the early period (39% and 38%, respectively), whereas more bacterial than viral infections were identified in the later period (56% vs. 19%, respectively) (Figure 2). Non-invasive testing for respiratory tract infection was performed in 34% of patients. These included nasopharyngeal swab for RSV/Influenza PCR in 16% (all negative), multiplex respiratory pathogen PCR in 5% (1 positive for coronavirus), and sputum culture in 21% (positive in 8 patients). This compares with the identification of an infectious pathogen via BAL in 36% of patients; bacterial in 16%, viral in 11%, and fungal in 10%. Transbronchoscopic lung biopsy biopsies were performed in 8 patients and provided diagnostic information in 3 patients (eosinophilic pneumonia, organizing pneumonia and diffuse alveolar damage each in 1 patient). Procedural complications occurred in 3 patients; 2 after transbronchoscopic lung biopsy (1 bleeding and 1 pneumothorax) and 1 during FOB-BAL (atrial fibrillation with rapid ventricular rate). In a multivariable logistic regression model, the underlying diagnosis, presence of acute respiratory failure, and early vs. later time period after HCT were independently affecting the diagnostic yield of FOB-BAL, with higher likelihood of DAH being diagnosed in patients with AML/MDS and during the early post-HCT period, and higher likelihood of DAH being diagnosed in patients with acute respiratory failure (Table 1). In 40% of patients, FOB-BAL findings lead to treatment changes. These included addition of antimicrobials in 24% and addition of corticosteroids in 22% (17% DAH, 2% idiopathic pneumonia syndrome, and 1% organizing pneumonia) (Figure 3). FOB findings lead to more antimicrobial modifications in the early than in the later period (32% vs. 18%, respectively). Overall survival was poor in all the three groups, although significantly better in patients with non-diagnostic FOB findings (median of 2, 3, and 11 months in patients with DAH, infection, or non-diagnostic FOB finings, respectively) (p = 0.03) (Figure 4). CONCLUSION FOB-BAL provides clinically useful information in the post-transplant period. BAL findings were diagnostic in 51% of patients, and led to management changes in 40% of patients. Transbronchoscopic lung biopsy is associated with higher rates of procedural complications. Further characterization of the underlying diagnosis in patients with non-diagnostic FOB-BAL findings remains an unmet clinical goal. Disclosures Sakemura: Humanigen: Patents &amp; Royalties. Kenderian:Morphosys: Research Funding; Kite/Gilead: Research Funding; Lentigen: Research Funding; Humanigen: Other: Scientific advisory board , Patents &amp; Royalties, Research Funding; Tolero: Research Funding; Novartis: Patents &amp; Royalties, Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.

Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors: A Report from the Center for International Blood and Marrow Transplant Research.

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.

Feasible outcome of blinatumomab followed by allogeneic hematopoietic cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first salvage.

In adult patients with relapsed or refractory (R/R) Philadelphia chromosome‐negative (Ph‐negative) B‐cell presursor acute lymphoblastic leukemia (BCP‐ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph‐negative BCP‐ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo‐HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1 <12 months. After the first blinatumomab cycle, 22 (68.8%) achieved CR. At the end of the second cycle, 20 of the 22 patients remained in persistent CR, and 1 patient achieved new CR. The overall minimal residual disease negativity rate was 75% among evaluable patients with persistent CR. Patients with CRD1 <12 months were associated with poorer response to blinatumomab. Twenty (62.5%) of 32 patients underwent allo‐HCT in blinatumomab‐induced CR. After a median follow‐up of 15.2 months, the 1‐year OS rates for all patients and patients receiving allo‐HCT in CR were 55.5% (median OS, 18.2 months) and 70.7%, respectively. Patients with CRD1 <12 months, extramedullary disease (EMD), and high peripheral blood blasts were associated with poorer OS. Blinatumomab is effective for achieving good quality CR and bridging to allo‐HCT for adult patients with R/R Ph‐negative BCP‐ALL in first salvage. The role of blinatumomab in patients with CRD1 <12 months, EMD, or high tumor burden should be evaluated in future trials.

1001. Feasibility and Outcomes of a Pre-Transplant Antibiotic Allergy Evaluation Program for Allogeneic Hematopoietic Cell Transplant (HCT) Candidates

BackgroundAntibiotic allergies impact the management of hematopoietic cell transplant (HCT) patients who are often prescribed antibiotics for infection prophylaxis and treatment. We evaluated the feasibility and outcomes of an antibiotic allergy evaluation program prior to allogeneic HCT.MethodsIn August 2017, we implemented a program to expedite allergy clinic referrals for adult allogeneic HCT candidates who reported an antibiotic allergy at their initial pre-transplant evaluation visit (PTEV). Allergy labels and clinical data including outcomes of allergy evaluation were prospectively collected for patients with PTEVs between 8/10/17 and November 15/18. The use of selected antibiotics was collected in the 100 days following HCT among patients with a reported β-lactam allergy (BLA). Choice of prophylactic agent for Pneumocystis jiroveci among patients with reported sulfa allergies was assessed among HCT recipients after engraftment.ResultsOf 276 allogeneic HCT candidates, 109 (39.5%) reported >= 1 antibiotic allergy (Table 1). Of the 109, 69 (63%) were referred for allergy evaluation; 83% (57/69) of those referred were evaluated at a median of 14 days after PTEV, and a median of 18 days before transplant. Among evaluated patients, 45 (79%) had >= 1 antibiotic allergy de-labeled including 74% (28/38) of those with BLA (Figure 1). Of the 10 patients whose BLAs could not be delabeled, 1 had a possible immediate IgE-mediated reaction, 5 had a delayed type IV hypersensitivity, and 4 had other reactions or required additional testing. Post-transplant antibiotic use among evaluated vs. nonevaluated patients reporting BLA is shown in Figure 2. Among 31 patients with reported sulfa allergies who underwent HCT, those who were evaluated received TMP-SMX rather than alternative prophylaxis more often (48%; 11/23) than those who were not evaluated (25%; 2/8). 10 (43%) of 23 evaluated patients were delabeled; 7 of 10 delabeled patients received TMP-SMX.ConclusionAntibiotic allergies are frequently reported among HCT candidates. Pre-transplant antibiotic allergy evaluation was feasible, led to de-labeling of the majority of reported allergies, and may alter antibiotic prescribing and increase the use of preferred agents following transplant. Disclosures All authors: No reported disclosures.

1761. A Single-Center Experience with Cidofovir for the Treatment of Double-Stranded (ds) DNA Viruses in Hematopoietic Cell Transplant (HCT) Recipients

BackgroundCidofovir (CDV), a nucleotide analog antiviral, is active against multiple dsDNA viruses relevant in HCT recipients. Despite a broad spectrum of activity, CDV utility is limited due to nephrotoxicity. We describe our experience with CDV in a large contemporary cohort from a single Institution.MethodsRetrospective review of adult HCT recipients who received CDV for any indication from 2011 to 2017. Initiation and duration of CDV treatment were at physicians’ discretion. CDV exposure and indications, Serum Creatinine (SCr) and outcomes were extracted from medical records and hospital databases.ResultsOf 1,235 HCT recipients, 54 (4.4%) received ≥1 dose of CDV. Stem cell source was peripheral blood in 39 (72%) patients, cord blood in 13 (24%) and marrow in 2(4%); 42 (78%) patients received CD34+ selected HCT. At CDV initiation, 23 (43%) patients had active GvHD and 16 (30%) received systemic steroids. CDV was started a median of 85.5 days (range 14–335) post HCT, given for a median of 3 doses (range 1–13) for a median of 2 weeks (range 1–17). Indications were adenovirus (ADV) infection in 35 patients, CMV in 19, BK virus in 21 and HHV6 in 3 patients. Nineteen (35%) patients had >1 dsDNA virus. Forty-one (76%) patients received CDV (3–5 mg/kg) once weekly, mainly for ADV or CMV, and 13 received CDV (≤1 mg/kg) once to thrice weekly, mostly for BK hemorrhagic cystitis (N = 12). Baseline sCr was mean 0.88 mg/dL (standard deviation [SD] = 0.37) at CDV initiation, mean 1.07 mg/dL at end of treatment (EOT) (SD = 0.57, N = 48, P = 0.004) and mean 1.23 mg/dL at EOT + 2 weeks (SD = 0.72, n = 28, P = 0.027). At EOT, 13 patients (24%) had acute kidney injury (AKI, ≥1.5-fold increase from baseline sCr). Of those, 12 (92%) received concomitant nephrotoxic drugs. AKI was attributed to other etiologies by treating physician in six patients. Of 51 patients with follow-up at EOT, 29 (57%) had clinical response to CDV treatment. Nineteen (35%) patients died ≤ 4 weeks from last CDV dose.Conclusion24% of highly immunocompromised HCT patients experienced AKI following CDV treatment for dsDNA viruses. The co-administration of nephrotoxic medications and the direct effect of infection limit our ability to assess the relative impact of CDV on renal function. Our data underscores the need for safer treatment options for HCT patients with life-threatening infections with dsDNA viruses. Disclosures All authors: No reported disclosures.

Autologous hematopoietic cell transplantation for acute myeloid leukemia in adults: 25years of experience in Japan.

Autologous hematopoietic cell transplantation (HCT) has not gained universal popularity in the treatment of acute myeloid leukemia (AML), and its status remains unclear. To determine the implementation status and outcomes of autologous HCT for adults with AML in Japan, we analyzed data from 1,174 patients (including 446 with acute promyelocytic leukemia [APL]) who underwent autologous HCT between 1992 and 2016 consecutively reported to the Japanese nationwide transplantation registry. The annual number of transplantations peaked at 82 cases in 1997, and has recently remained at around 40 cases. The percentage of APL has increased sharply since 2004, and currently exceeds 70%. While most non-APL patients underwent autologous HCT during first complete remission (CR), transplantation during second CR has become mainstream for APL patients since the early 2000s. The 5-year survival, relapse, and non-relapse mortality rates were 55.3%, 42.1%, and 8.6% for non-APL patients, and 87.6%, 12.9%, and 3.4% for APL patients, respectively. Patients transplanted in the later period showed better survival than those transplanted in the earlier period, both for non-APL (P < 0.001) and APL (P = 0.036). These results clearly show the various changes in transplantation practice and post-transplant outcomes in Japan over the past 25years.

Infectious complications in children and adults with hematological malignancies

AbstractInfections are the main cause of morbidity and mortality in pediatric hematology and oncology (PHO) and hematopoietic cell transplantation (HCT) settings in children and adults. The analysis of incidence and outcome of bacterial, fungal, and viral infections in Polish PHO/ HCT centers was performed over a period of 72 months (2012–2017). The summary of infections in 5628 patients with newly diagnosed malignancy and 971 HCTs is presented in this paper. Additionally, data of 650 pediatric HCTs from 2012 to 2015 were compared with the data of 3200 HCTs in adults. The risk of any infection per patient was higher in HCT vs PHO patients (2062/971 vs 7115/5628; 2.1 vs 1.3; HR=1.7, p&lt;0.0001). The incidence of bacterial infections was 34,2±0,6% in PHO vs 41,5±1,6% in HCT patients, and the outcome was better in PHO patients: 97,9±0,2% vs 91,8±1,0%. The incidence of patients with fungal infection was 8,8±0,4% vs 21,2±1,3%, and the outcome was better in PHO patients: 95,9±0,7% vs 85,8±2,3%. Incidence of viral infections was 5,0±1,0% in PHO setting, including part of previously transplanted patients, and 47,8±2,2% in HCT setting (60,9±2,3% allo-HCT; 5,6±1,3% auto-HCT). In children, the incidence was higher for bacterial (36.0% vs 27.6%), fungal (25.3% vs 6.3%), and viral (56.3% vs 29.3% allo-HCT; 6.6% vs 0.8% auto-HCT) infections than in adults (p&lt;0.0001), and the outcome was better for bacterial (95.5% vs 91.4%), fungal (88.0% vs 74.9%), and viral (98.6% vs 92.3%) infections. In conclusion, the presented large studies have determined the incidence of infectious complications and their outcomes in HCT and PHO centers in Poland.

Histologic and clinical cross-sectional study of chronic hair loss in patients with cutaneous chronic graft-versus-host disease

While scalp alopecia represents a distinctive feature of chronic graft-versus-host disease (cGVHD), little is known about the clinical and histologic presentation of hair loss. We sought to classify the clinical presentations and histologic findings of chronic hair loss in patients with cutaneous cGVHD. A prospective cohort of 17 adult hematopoietic cell transplantation (HCT) recipients with cutaneous cGVHD was enrolled. Dermatologic examinations were performed, and punch biopsy specimens of the scalp were obtained. Biopsy specimens were analyzed with hematoxylin-eosin and immunohistochemical stains in all cases and fluorescence in situ hybridization analyses in specific cases. Clinically, 4 patterns of hair loss were described-patchy nonscarring (41.2%), diffuse nonscarring (11.8%), diffuse sclerotic (11.8%), and patchy sclerotic (5.9%). The location of the inflammatory infiltrate on hematoxylin-eosin-stained specimens correlated with the hair loss pattern patients had clinically, with cell populations around the bulb and bulge in nonscarring and sclerotic cases, respectively. Fluorescence in situ hybridization studies in female cGVHD patients with male donors demonstrated green Y chromosomes limited to the area of the hair follicle affected by inflammatory cells. This study describes the various clinical and histologic subtypes of long-standing alopecia in adult cGVHD patients and suggests that this alopecia may be a direct manifestation of cGVHD of the hair follicle.