Autologous Hematopoietic Cell Transplantation Recipients Research Articles

The effect of gastrointestinal graft-versus-host disease and diarrhea on the pharmacokinetic profile of sotrovimab in hematopoietic stem cell transplant recipients.

Monoclonal antibodies (mAbs) are utilized broadly to treat cancer and infectious diseases, and mAb exposure (serum concentration over time) is one predictor of overall treatment efficacy. Herein, we present findings from a clinical trial evaluating the pharmacokinetics (PK) of the long-acting mAb sotrovimab targeting SARS-CoV-2 in hematopoietic cell transplant (HCT) recipients. All participants received an intravenous infusion of sotrovimab within one week prior to initiating the pre-transplant preparative regimen. The serum concentration of sotrovimab was measured longitudinally for up to 24 weeks post-transplant. Compared to non-HCT participants, we found that mAb clearance was 10% and 26% higher in autologous and allogeneic HCT recipients, respectively. Overall sotrovimab exposure was approximately 15% lower in HCT recipients compared to non-HCT recipients. Exposure was significantly reduced in HCT recipients who developed diarrhea and lower gastrointestinal (GI) graft-versus-host disease (GVHD) post-transplant. These data show that sotrovimab exposure may be reduced in HCT recipients, possibly related to increased GI clearance in patients with GVHD. This phenomenon has implications for dose selection and duration of efficacy with sotrovimab and potentially other mAbs in this vulnerable patient population. Thus, mAb dose regimens developed in non-HCT populations may have to be optimized when applied to HCT populations.

Return to school practices after hematopoietic cell transplantation: a survey of transplant centers in the United States.

To understand transplant center recommendations on return-to-school timing and related support for hematopoietic cell transplant (HCT) survivors, we conducted a two-phase, cross-sectional, web-based survey: In Phase I, medical directors of pediatric HCT centers from the National Marrow Donor Program/ Be The Match Registry were asked regarding the availability of a return to school standardized operating procedure (SOP). In Phase II, HCT physician members of the Pediatric Transplantation and Cellular Therapy Consortium were approached to study inter-physician practice variability regarding return to school post-HCT, factors affecting their decision-making, and support provided by HCT centers for return to school. Out of 46 respondents in Phase I (55% response rate), 28 (61%) reported having a SOP. Wide variations in recommendations were noted in 12 received SOPs. In Phase II, 122 physicians (60 centers) responded (30.6% response rate). The majority (60%) recommended autologous HCT recipients return to school within 6 months post-HCT but 65% recommended allogeneic HCT recipients return to school after 6 months or once off immunosuppression. Our findings indicate a lack of consensus within and across HCT centers regarding recommended return to school timing and underscore need for a guideline to standardize this process to ensure patient safety and re-integration into school.

Compliance with yellow fever and measles vaccines in the revaccination program post-hematopoietic cell transplantation.

Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p<.0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.

Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Hematopoietic Cell Transplantation and Cellular Therapies: A Retrospective Monocenter Real-Life Analysis.

(1) Background: Autologous, allogeneic hematopoietic cell transplantation (HCT) and other cellular therapies, including CAR T cell and gene therapy, constitute a cornerstone in the management of various benign and malignant hematological disorders. Invasive fungal infections (IFD) remain a significant cause of morbidity and mortality in HCT recipients. Therefore, we investigated the prevalence and risk factors of IFD following HCT and other cellular therapies in an era of novel antifungal prophylaxis. (2) Methods: In this study, we retrospectively enrolled adult HCT recipients who were treated at our JACIE-accredited center according to standard operating procedures over the last decade (2013-2022). (3) Results: 950 patients who received cellular therapies were studied. None of the 19 CAR T cell and neither of the two gene therapy recipients developed IFD whereas 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Overall, 11 patients who received allogeneic HCT experienced probable IFD, possible IFD was found in 31/473, and IFD was proven in 10/473. A second IFD episode was present in three patients. Four-year OS was significantly lower in proven compared to probable IFD (p = 0.041) and was independently associated with HCT-CI (p = 0.040) and chronic GVHD (p = 0.045). (4) Conclusions: In this real-world cohort, the prevalence of proven and probable IFD in an era of novel antifungal prophylaxis was found to be relatively low. However, IFDs were associated with poor outcomes for patients who received allogeneic HCT.

Viral Encephalitis after Hematopoietic Cell Transplantation: A Systematic Review

Viral encephalitis is a rare but serious complication after hematopoietic cell transplantation (HCT). The nonspecific early signs and symptoms and rapid progression can make it difficult to diagnose and treat in a timely fashion. To better inform clinical decision making in post-HCT viral encephalitis, a systematic review of prior studies of viral encephalitis was performed, with the goal of characterizing the frequency of various infectious etiologies and their clinical course, including treatments and outcomes. A systematic review of studies of viral encephalitis was performed. Studies were included if they described a cohort of HCT recipients who were tested for at least 1 pathogen. Of 1613 unique articles initially identified, 68 met the inclusion criteria, with a total of 72,423 patients studied. A total of 778 cases of encephalitis were reported (1.1%). Human herpesvirus 6 (HHV-6) (n=596), Epstein-Barr virus (n=76), and cytomegalovirus (n=33) were the most commonly reported causes of encephalitis, and HHV-6 encephalitis tended to occur the earliest, accounting for most cases prior to day +100 post-transplantation. Of 29,671 patients with available transplantation data, encephalitis was diagnosed in 282 of 4707 (6.0%) cord blood transplantation (CBT) recipients, in 372 of 24,664 (1.5%) non-CBT allogeneic HCT recipients, and in 5 of 300 (1.7%) autologous HCT recipients. Of the 282 CBT encephalitis cases, 270 (95.7%) were caused by HHV-6. Overall, 288 (37.0%) of the 778 patients with encephalitis died, and 75 deaths were attributable to encephalitis, with the time between diagnosis and death ranging from 3 to 192 days. Viral encephalitis occurs in approximately 1% of HCT recipients, and HHV-6 is the most common cause. Mortality following encephalitis in HCT recipients is high, indicating an urgent need for advancement in preventive and therapeutic strategies.

Successful restoration of protective immunity against measles, mumps, and rubella following MMR vaccination in adult hematopoietic cell transplant recipients.

The optimal number of doses as well as the role for measurement of postvaccination titers after measles, mumps, rubella (MMR) vaccination in adult hematopoietic cell transplantation (HCT) recipients remains unknown. In the present study, we assessed humoral immunity against measles, mumps and rubella before and after MMR vaccination in 187 adults who received at least one dose of the MMR vaccine after HCT. Among those with baseline titers, posttransplant prevaccination seroprotection rates were 56%, 30%, and 54% for measles, mumps, and rubella, respectively; and significantly lower in allogeneic versus autologous HCT recipients for measles (39%vs. 80%, p = .0001), mumps (22%vs. 41%; p = .02) and rubella (48%vs. 62%, p = .12). Among those who were seronegative at baseline, seroconversion rates after one dose of MMR were 69%, 56%, and 97% for measles, mumps, and rubella, respectively. Seronegative patients after one dose of MMR (i.e., nonresponders) seroconverted for measles and mumps after a second MMR vaccine dose. Our findings demonstrate successful restoration of protective immunity against measles, mumps, and rubella after vaccination in adult HCT recipients; one dose of MMR elicited protective titers in the majority of patients, and a second vaccine dose was immunogenic in nonresponders.

Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Non-Hodgkin Lymphoma: Secondary Analysis from Two Multi-Center Randomized Controlled Trials of Hematopoietic Cell Transplant Survivorship Interventions

Background: Autologous hematopoietic cell transplantation (AHCT) recipients with Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL) who survive progression-free for ≥2years can expect a 5-year overall survival rate of 90% (Myers et al, Cancer, 2018). However, patient-reported outcomes (PROs) in long-term lymphoma survivors after AHCT have not been well described. We present secondary analyses from a combined baseline dataset from two multi-center randomized clinical trials of HCT survivorship interventions, enrolling at 18 US transplant centers, including a large cohort of 1-10-year lymphoma AHCT survivors. Our objectives were to describe health-related quality of life (HRQoL) and cancer and treatment-related distress (CTXD), and to examine their associations with available clinical and sociodemographic correlates. Methods: Cross-sectional data at the time of study enrollment were pooled from two trials: SCP (Survivorship Care Plan; NCT02200133) and INSPIRE (INternet Survivorship Program with Information and REsources; NCT01602211). The SCP study enrolled patients (N=456) who were in a stable remission 1-5 years after transplant and the INSPIRE study enrolled survivors (N=1177) who were 2-10 years post-transplant, between 2003-2014. This analysis was restricted to AHCT recipients with diagnosis of HL or NHL. Our objectives were to describe HRQoL and cancer related distress (CTXD), and to examine their association with available baseline correlates. HRQoL was assessed using SF-12 v2 (12-item short survey form) and described as physical component summary (PCS) and mental component summary (MCS) T-scores (higher scores indicated better functioning). Comparisons between SF-12 scores and age-matched population norm (mean score 50, standard deviation [SD] 10) were analyzed using paired t-tests. Distress was assessed using the CTXD instrument, which reports mean scores from 0 to 3, with higher scores indicating greater distress. Based on prior receiver operating characteristic analysis, CTXD score >1.1 was considered clinically significant. Multivariate linear regression models were performed to evaluate the association of PCS score, MCS score, and CTXD with the following variables: diagnosis (HL vs. NHL), sex, race/ethnicity, number of HCT, use of total body irradiation (TBI) for AHCT, subsequent allogeneic transplant, age at time of enrollment, and time since AHCT. Results: Of 522 HL and NHL AHCT recipients, 60% were male, 94% were Caucasian, 94 (18%) had HL, 428 (82%) had NHL; 26 (5%) received >1 HCT, including 16 (4%) who received a subsequent allogeneic HCT. 8% patients received TBI-based conditioning regimens. Median age at index AHCT was 55 (range: 17-80) years, and median time from AHCT to study entry was 5 (range: 2-11) years. The mean [±SD] PCS T-score in the study population (48.96 [±10.59]) was slightly lower than the population norm (50 [±10]) (p=0.03). Mean [±SD] MCS T-scores were not significantly different between patients (50.75 [±10.40]) and general population (50 [±10]) (p=0.16) (Figure 1). The mean CTXD score was 0.79 (±0.59), with 135 (26%) patients reporting clinically significant distress (mean score ≥ 1.1). Among CTXD domains, "health burden” and "uncertainty” accounted for the highest burden of clinically significant distress, with 42% and 35% of patients reporting distress in these domains, respectively (Figure 2). On multivariable analysis, older age at study entry was associated with higher MCS score (estimated slope: 1.3 [95% CI: 0.5-2.2]; p=0.002), although there was no association of age with PCS score or CTXD. We did not observe associations of other variables and PCS score, MCS score, or CTXD. Conclusions: Patients with HL and NHL who are long-term disease-free survivors of AHCT have lower physical HRQoL compared to general population, although the difference is not clinically meaningful. Mental HRQoL in HL and NHL AHCT survivors is similar to general population. Older age is associated with higher mental HRQoL. Approximately a quarter of patients report clinically significant cancer and treatment-related distress. Survivorship programs should continue to screen for, and address concerns regarding HRQoL and distress. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Subsequent Solid Neoplasms Following Hematopoietic Cell Transplantation (HCT) for Hematologic Malignancies: Comparing Center for International Blood and Marrow Transplant Research (CIBMTR) and California Cancer Registry (CCR) Data

Introduction: Subsequent neoplasms (SN) represent a leading cause of non-relapse mortality among hematopoietic cell transplantation (HCT) survivors. Treatment advances and expanded access for older patients have resulted in a growing population of HCT survivors. Changes in the clinical approaches to HCT, including the introduction of reduced-intensity conditioning regimens, have changed the landscape of potential SN risk factors. The Center for International Blood and Marrow Transplant Research (CIBMTR) collects extensive patient, procedure, and outcome data from HCT centers in the United States and abroad and serves as a key resource for quantifying SN incidence and identifying risk factors. The completeness of SN and other late effects reported to the CIBMTR is uncertain because patients may not continue follow-up care, particularly long-term care, at HCT centers. The California Cancer Registry (CCR) is a statewide population-based cancer registry which is estimated to capture 99% of all cancer diagnoses occurring among state residents. We compared the distribution and cumulative incidence of solid SNs within a cohort of individuals who underwent HCT for hematologic malignancy reported to the CIBMTR and linked to the California Cancer Registry (CCR). Methods: The study population included 18,450 California residents from the CIBMTR (8,232 allogeneic and 10,218 autologous HCT recipients) who were diagnosed with a hematologic malignancy between 1991-2016, linked to the CCR, and had known dates of first HCT, death (if deceased), or last known date alive. Patients were followed from the date of first HCT until the earliest of a second HCT, death, or date last known alive according to either source. ICD-O-3 histology and topography codes were used to identify and classify solid tumors in the CCR according to 10 broad types available from CIBMTR (see Table 1 below). We excluded non-melanoma skin cancers, as cutaneous basal and squamous cell carcinomas are not reportable to the CCR. We matched reports of solid SNs from the two sources according to type and diagnosis date. Cumulative incidence of developing a solid SN, accounting for the competing risk of death, was estimated from CCR and CIBMTR separately and using both data sources. Results: During a median time since HCT of 2.4 years (range: 0.003 to 27.4 years), CIBMTR and CCR reported solid SNs among 518 and 641 HCT survivors, respectively. In CCR, 7.5% of patients with an SN (48/641) had more than one type of SN; in CIBMTR the corresponding estimate was 4.1% (21/518). Among 775 unique patients with at least one solid SN from either source, 384 (49.6%) had an SN reported from both sources, 257 (33.2%) from CCR only and 134 (17.3%) from CIBMTR only. As patients could have multiple SN types, the combined dataset included 871 solid SNs, of which 38.0% were found in CCR only, 20.6% in CIBMTR only, 38.1% were found in both sources and had diagnosis dates within 90 days, and the remaining 3.3% were found in both sources but had discrepant dates (Table 1). The proportion of SNs found in both sources varied by HCT type, SN type, calendar year of SN diagnosis, and time since first HCT. Specifically, the proportion identified in both sources was higher after autologous than allogeneic HCT. By SN type, >50% of SNs of the lung, thyroid, GU system, and breast were found in both sources; a majority of sarcomas and SNs of the oral cavity/pharynx and CNS tumors were found in CCR only; and other/poorly specified SN types were more likely to be found in CIBMTR only, driven by poorly specified SNs. The proportion of cases found in both sources and concordant on diagnosis date was lower for SNs diagnosed in earlier calendar years (<2010) and those occurring >10 years since HCT. The cumulative incidence of developing a solid SN at 10 years following a first HCT was 4.4% (95% cumulative incidence [CI] 3.9%-4.8%) based on CIBMTR information, 5.6% (95% CI] 5.1% to 6.1%) based on CCR information, and 6.6% (95% CI 6.1%-7.2%) based on both sources combined (Figure 1). Conclusion: In this linkage of CIBMTR data with population-based cancer registry data, 38.0% of solid SNs were found in CCR only, 20.6% in CIBMTR only, and 41.4% in both sources. These analyses suggest that linkage of these high-quality data sources can offer a more complete assessment of the burden of solid SNs among HCT survivors. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk Factors, Prevalence, and Outcomes of Invasive Fungal Disease Post Cellular Therapies: A Real-World Analysis

Objective: Cellular therapies, including CAR-T cell, gene therapy, autologous and allogeneic hematopoietic cell transplantation (HCT), remain a cornerstone in management of various benign and malignant disorders. Despite intensified efforts to improve strategies, invasive fungal infections (IFD) remain an important cause of morbidity and mortality. Therefore, we investigated risk factors, prevalence, and outcome of IFD in the era of novel anti-fungal prophylaxis. Methods: We retrospectively enrolled consecutive adult patients that underwent cellular therapies at our JACIE-accredited center according to standard operating procedures (2013-2022). We defined IFD according to current consensus (2020) and guidance on imaging (2021, EORTC). We analyzed the following factors: age, disease, donor, HLA matching, conditioning, graft, severe acute and moderate/severe chronic GVHD, antifungal prophylaxis, immunosuppressants, IFD type (according to current consensus), galactomannan/β-D-glucan, cultures, imaging, bacterial/viral infections, IFD treatment, relapse, and overall survival (OS). Results: We studied 950 recipients of cellular therapies (19 CAR-T cell and 2 gene therapies, 456 autologous and 473 allogeneic HCT). No CAR-T cell and gene therapy patient developed IFD; while 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Further analysis was performed only in allogeneic HCT recipients. Possible IFD was documented in 31/473 at a median of 112 (range 7-1353) post-transplant day, probable in 11/473 (5: positive galactomannan, 6: positive cultures) at 154 (12-469), proven in 10/473 (3: positive galactomannan, 7: positive cultures) at 226 (25-1146) day. Concurrence of bacterial or viral infection was documented in 20/52 and 17/52 patients respectively. Second IFD episode occurred in 3 patients (1: probable, 2: proven IFD), that succumbed to TRM (1) and relapse (2). Candida species were isolated in 9 patients, Fusarium in 2 and Aspergillus in 2. Mucormycosis was diagnosed in 2 patients, while the remaining IFD were attributed to aspergillosis. During the aplastic period, caspofungin had been administered as primary prophylaxis (41/52) and amphotericin as secondary prophylaxis (11/52), which were then changed to posaconazole and isavuconazole respectively for the immunosuppression period. Independent risk factors for IFD were type of donor (20% in alternative, 12% in unrelated, and 5% in sibling donors, p=0.006) and moderate/severe chronic GVHD (15% versus 8%, p=0.029). Five-year OS was significantly lower in patients with IFD, especially those with proven IFD (p=0.041). IFD remained a predictor of OS (p=0.044) independently of donor type and chronic GVHD. Conclusions: Our large real-world cohort indicates the relatively low prevalence of proven IFD in the era of novel antifungal prophylaxis, which is however associated with poor outcomes in allogeneic HCT recipients. Possible IFD, assessed by host and clinical factors including updated documentation of imaging, has shown similar outcomes to probable IFD. Therefore, wider application of sensitive mycological testing is needed for high-risk populations, such as alternative alloHCT recipients or chronic GVHD patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lessons Learned from COVID-19 Pandemic: Outcomes after Sars-Cov-2 Infection in Hematopoietic Cell Transplant and Cell Therapy Recipients

Background: Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020. Over 500 million cases of SARS-CoV-2 have been reported worldwide, with over 90 million being in the US. More than 6 million lives, with over 1 million only from the US, have been claimed by the pandemic. Hematopoietic cell transplant (HCT) or chimeric antigen receptor-T (CART) cell therapy recipients have a higher risk of mortality with COVID-19. In this updated analysis, we investigated the outcomes after SARS-CoV-2 infection in HCT/CART recipients. Methods: We conducted a single-center prospective study, including all (n=196) adult HCT/CART recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center from March 2020 to March 2022. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using the chi-square and t-test, were performed. Kaplan-Meier and cox regression analyses were conducted. Results: The study included 196 HCT/CART recipients who acquired SARS-CoV-2 infection, including allogeneic HCT (n=91, 46%), autologous HCT (n=89, 46%), and CART (n=16, 8%) recipients. The median age was 59.8 (21.9-79.5) years; 76.5% were Caucasians and 58% were males. The median time since HCT/CART to SARS-CoV-2 infection was 25.4 (0.2-201.9) months, and 12% of patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T. Plasma cell (37%), myeloid (34%), lymphoid (28%) or solid (1%) malignancies were primary diagnoses. Myeloablative conditioning was performed in 64% of patients. Donors were autologous (53%), matched sibling (12%), matched unrelated (21%), and haploidentical (14%). Prior acute graft-versus-host disease (GVHD), prior chronic GVHD, active GVHD, and current immunosuppressive therapy (IST) were noted in 20%, 26.5%, 23.5%, and 25.5% of patients respectively. Concurrent infections were observed in 12% of patients. COVID-19 severity was mild (n=136, 70%), moderate (n=24, 12%), severe (n=20, 10%) or critical/fatal (n=16, 8%). Clinical findings included pneumonia or abnormal chest imaging (31%), hypoxia (19%), intensive care unit admission (9%), and mechanical ventilation (6%). Therapies included remdesivir (31%), convalescent plasma (11%), dexamethasone (15%), monoclonal antibodies (32%), and tocilizumab/baricitinib (5%). At least one dose of SARS-CoV-2 vaccine was reported in 70% of patients (45% pre-COVID, 25% post-COVID) while 3% of patients had received pre-exposure prophylaxis. The median duration of viral shedding (positive SARS-CoV-2 PCR) was 6.5 (0.3-23.4) weeks. After a median follow-up of 5.4 (0.3-24.8) months, the mortality rate was 12% with COVID-specific mortality of 8%. Of allogeneic HCT patients, 18% (n=16) developed subsequent GVHD after COVID-19 requiring systemic steroids and additional immunosuppression. Eighty-four (43%) patients were diagnosed with COVID after Sep 2021 and had the lowest COVID-specific mortality (2% compared to 12.5% in preceding months of the pandemic). Significant predictors of COVID-19 mortality included allogeneic HCT (HR 3.7, 95% CI 1.2-11.6, p=0.023), COVID-19 within 100 days of HCT/CART (HR 4.8, 95% CI 1.7-13.2, p=0.002), COVID-19 diagnosis earlier in the pandemic (HR 5.2, 95% CI 1.1-24.4, p=0.037), prior acute GVHD (HR 3.2, 95% CI 1.2-8.5, p=0.022), active GVHD (HR 3.5, 95% CI 1.3-9.2, p=0.013), and concurrent IST (OR 7.0, 95% CI 2.4-20.1, p<0.001) while prior SARS-CoV-2 vaccination significantly reduced the COVID-19 mortality (HR 0.19, 95% CO 0.05-0.68, p=0.010). In 15 patients with available data, vaccination induced protective anti-spike protein antibody response (>100 U/mL) in 67% of patients with a median titer of 656 (9-688,000) U/mL after completion of the primary vaccination series. Conclusion: Hematopoietic stem cell transplant and CART cell therapy recipients have a higher risk of morbidity and mortality with SARS-CoV-2 infection. Our findings highlight factors associated with COVID-19 mortality in HCT/CAR-T recipients. In HCT/CART recipients, strict vigilance, infection prevention measures, vaccination prioritization, close monitoring, and early aggressive treatment interventions are suggested for COVID-19 and future emerging infectious diseases. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pilot Trial of Homebound Hematopoietic Cell Transplantation

For eligible patients with multiple myeloma (MM) and amyloid light chain (AL) amyloidosis, high-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) is a standard and widely used consolidation therapy. Autologous HCT requires specialized care at a transplantation center and investment from patients and caregivers. We studied the safety and feasibility of delivering transplantation care in a homebound setting to decrease the burden of therapy and increase access to autologous HCT. Patients with MM and AL amyloidosis undergoing autologous HCT were eligible if they resided in designated ZIP codes and had a full-time caregiver, Wi-Fi connection, HCT Comorbidity Index ≤3, and Karnofsky Performance Status score ≥80. High-dose melphalan (on day -2) and hematopoietic cell reinfusion (day 0) were administered in the outpatient clinic. Protocol-specific home care was provided from day +1 through engraftment. Patients were assessed and blood was drawn daily by advanced practice providers. Interventions were delivered by registered nurses. Attending physicians communicated daily through telemedicine. Quality of life, patient and caregiver satisfaction, and fecal microbiota profiling data were collected. Fifteen patients were enrolled and received transplantation care at home starting on day +1 following hematopoietic cell infusion. Patients remained in the program for an average of 12 days and required an average of 2 outpatient visits while receiving home care. Seven of 15 patients were admitted for a median of 4 days (range, 3 to 10 days); admission occurred on day +7 in 5 patients, on day +8 in 1 patient, and on day +12 in 1 patient for neutropenic fever in 2 patients, fever attributed to engraftment syndrome in 2 patients, diarrhea in 2 patients, and dehydration in 1 patient. Only 1 patient had a documented infection (Clostridioides difficile). One patient admitted with neutropenic fever required intensive care unit admission for a gastrointestinal bleed. Forty-seven percent of the patients experienced a grade ≥3 nonhematologic toxicity. There were no deaths on the study. Patients and caregivers reported high satisfaction with care. Microbiota diversity patterns were similar to those of autologous HCT recipients who did not receive post-HCT care at home, although a subset of the cohort maintained microbiota diversity throughout. Homebound HCT in an urban setting is safe and feasible, with less than one-half of patients requiring inpatient admission. Despite increased patient and caregiver responsibility in the homebound setting compared with an inpatient setting, patient and caregiver satisfaction was high. These results support expansion of homebound transplantation care programs.

High Proliferating Regulatory T Cells Post-Transplantation Are Associated with Poor Survival in Lymphoma Patients Treated with Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic cell transplantation (AHCT) in lymphoma is well established and yields improved survival for patients with chemotherapy-sensitive disease. The patterns of immune cell reconstitution after AHCT have emerged as independent predictors of clinical outcomes. We sought to analyze the patterns of regulatory T cell (Treg) reconstitution after AHCT in non-Hodgkin lymphoma (NHL) and their correlations with clinical outcomes. In our prospective cohort study, we analyzed patterns of lymphocyte reconstitution and focused on T reg subsets for 41 patients who underwent AHCT for NHL between 2010 and 2016. Flow cytometry analysis was performed on blood samples collected prospectively at days +28, +60, and +100 post-AHCT. Patients' overall survival (OS) and progression-free survival (PFS) were correlated with Treg immune cell reconstitution. At day +28, Tregs comprised a median of 2.7% (range, 0.4% to 16.8%) of the total lymphocyte population. The proportion of proliferating Tregs (Ki67+ Tregs) varied widely from 6.3% to 59.2% (median, 16.1%) of total Tregs and has a significant effect on post-transplantation outcomes. AHCT recipients with low levels of proliferating Tregs (ie, <16.1%, Ki67+ Tregs) at 28 days had better 5-year OS compared to patients with high Ki67+ Treg levels (75% versus 42%; P=.01). Higher levels of proliferating Tregs at day +28 post-AHCT were associated with higher mortality, with the most frequent cause of death due to lymphoma progression. This association suggests that immunosuppressive cellular reconstitution adversely impacts survival in AHCT recipients with NHL.

A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature.

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search. Most studies reporting on adults and pediatric recipients described signs and symptoms that were typical of COVID-19. Overall, the mortality rates were high, with 21% of adults and 6% of pediatric HCT recipients succumbing to COVID-19. The factors reported to be associated with increased mortality included age (HR = 1.21, 95% CI 1.03–1.43, p = 0.02), ICU admission (HR = 4.42, 95% CI 2.25–8.65, p < 0.001 and HR = 2.26, 95% CI 1.22–4.20, p = 0.01 for allogeneic and autologous HCT recipients), and low platelet count (OR = 21.37, 95% CI 1.71–267.11, p = 0.01). Performance status was associated with decreased mortality (HR = 0.83, 95% CI 0.74–0.93, p = 0.001). A broad range of treatments was described, although no controlled studies were identified. The risk of bias, using the Newcastle–Ottawa scale, was low. Patients undergoing HCT are at a high risk of severe morbidity and mortality associated with COVID-19. Controlled studies investigating potential treatments are required to determine the efficacy and safety in this population.

Community Health Status and Long-Term Outcomes in 1-Year Survivors of Autologous and Allogeneic Hematopoietic Cell Transplantation

Background: Race/ethnicity and socioeconomic status (SES) have been associated with access to and outcomes after hematopoietic cell transplantation (HCT). The role of health disparity factors beyond race/SES in HCT outcomes, however, has not been well described. This is especially true for long-term HCT survivors, for whom local socio-demographic factors may have a greater impact on outcomes because patients may no longer be under close monitoring of their transplant center. The County Health Rankings and Roadmaps (CHRR) provides updated aggregated information from several publicly available datasets to comprehensively describe the health status of US counties. A recent report demonstrated an association between community health status and 1-year non-relapse mortality in a CIBMTR cohort of allogeneic HCT recipients (Hong et al., Cancer 2021). We conducted a single-center retrospective cohort study to investigate the association between community health and long-term outcomes in 1-year autologous and allogeneic HCT survivors.Methods: Our study included 1,812 consecutive adult patients from Cleveland Clinic's BMT Program database who received their first allogeneic or autologous HCT between 2003 and 2017 and survived at least 1 year after their transplant. We used patient community risk score (PCS) as the surrogate for community health. PCS was nationally standardized and calculated as the sum of weighted Z-scores of the 23 county-level community health factors considered in CHRR. The 23 factors fell under 4 categories of health factors: health behavior (tobacco and alcohol use, etc.), clinical care (access and quality of care), social and economic factors (education, community safety, etc.), and physical environment (environmental quality and built environment). Higher PCS indicate worse community health. We evaluated the association of PCS with overall survival (OS), relapse, and non-relapse mortality (NRM) with Cox or Fine and Gray regression separately for autologous and allogeneic HCTs. Considered co-variables included pre-transplant sociodemographic data, disease diagnosis, and transplant factors.Results: Autologous HCT recipients (n=1,313) lived in 133 of 3,141 CHRR counties, 90% in Ohio. Similarly, allogeneic recipients (n=499) were from 88 counties, 88% in Ohio. Patient characteristics are shown in Table 1. The median (range) PCS scores for autologous and allogeneic HCT recipients were 0.03 (-0.85, 0.97) and 0.03 (-0.85, 0.58), respectively. For comparison, the PCS for the complete US CHRR dataset ranged from -1.43 to 2.54 and ranged from -1.6 to 2.0 in the prior CIBMTR study that included allogeneic HCT recipients (Hong et al., Cancer 2021). PCS was not associated with OS, relapse, or NRM for autologous or allogeneic HCT recipients in univariable analysis, nor were the four categories of health factors that contribute to the total PCS (Table 2). In addition, race and estimated median household income were not associated with mortality. Similar findings were noted in multivariable analysis.Conclusion: In our single center study, PCS was not associated with OS, relapse, or NRM in allogeneic or autologous HCT recipients who survived at least 1 year after HCT. A limitation of our analysis is that our cohort represented a single center with regional representation, where long-term follow up care is provided through a dedicated survivorship clinic and there is a strong emphasis on psychosocial support. A national cohort with greater geographical diversity is needed to better define the association of community factors and outcomes in long-term HCT survivors. [Display omitted] DisclosuresHamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Majhail: Anthem, Inc: Consultancy; Incyte Corporation: Consultancy.

Trends in Use and Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Racial/Ethnic Minorities

BackgroundThere has been an increase in overall utilization as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for most hematologic disorders over time. It is not known if these changes have impacted racial/ethnic minorities equally. In this study, we describe changes in the volume and rate of autologous (auto) and allogeneic (allo) HCT and examine trends in survival in different racial/ethnic groups from 2009 to 2018.MethodsData were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) which collects patient data on most autologous and allogeneic HCT recipients in the US. We compared the number of auto and allo transplants in 4 different racial/ethnic groups: Non-Hispanic Whites (NHWs), African Americans (AAs), Hispanics and ‘Others’ across five 2-year cohorts from 2009 to 2018. ‘Others’ included Asians, Pacific Islanders and Native Americans as well as non-US residents. Since numbers in individual categories were too low to be meaningful, they were grouped together as ‘Others’. Multi race individuals and those with either race or ethnicity missing were excluded. Cox proportional hazards models were used to examine trends in overall mortality after auto HCT in adult patients (for NHL, HD, and MM), and allo HCT among adult and pediatric patients (for AML, ALL, lymphoma including chronic lymphocytic leukemia, and MDS/MPD) in the 4 different racial ethnic groups over 5 study time periods. These models were adjusted for sociodemographic and clinical variables (age, sex, Karnofsky/Lansky score, HCT-comorbidity index, disease, disease status, geographic region, insurance, marital status, education, distance to the transplant center, median income derived from patient's ZIP code). Graft type, donor, conditioning, GVHD prophylaxis, donor-recipient CMV match and donor-recipient sex match were included for allo HCT models.ResultsA total of 80,080 (59,666 NHWs, 10,683 AAs, 7,110 Hispanics) patients received an auto HCT and 60,412 (44,272 NHWs, 4,964 AAs, 7,826 Hispanics) received an allo HCTs from 2009 to 2018. The volume of auto and allo transplants increased overall, as well as within each race/ethnicity group, over the study periods. In addition, there was a significant change in the proportion of patients in each racial/ethnic group undergoing an auto HCT, with a lower proportion of NHWs and increased proportion of minorities over time (from 78%, 12% and 8% in 2009 -2010 to 71%, 15% and 10% in 2017-2018 for NHWs, AAs and Hispanics respectively; p<0.001). Similar trends were observed for allo HCT: from 76%, 8% and 12% in 2009-2010 to 71%, 9% and 14% in 2017-2018 of all allo HCTs for NHWs, AAs and Hispanics respectively; p<0.001. While there was an increase in the rate of transplants over the years across all racial/ethnic groups, the rate was higher in AAs and Hispanics as compared to NHWs (Table 1).There was no significant difference in overall mortality amongst the three main racial ethnic groups, though there was decrease in mortality over time for auto HCT and adult allo HCT patients. In the allo HCT pediatric group, AAs had higher overall mortality as compared to NHWs across all time periods. (Table 2) Figure 1 shows temporal trends in two-year survival by race and ethnicity.ConclusionsThis large population-based study shows an improvement in the rates and survival of auto and allo HCT in adults over time. Changes in the proportion of different racial/ethnic groups undergoing HCT are higher than rate of change of population growth (3% decline for NHWs, no change in AAs and 2% increase in Hispanics from 2010 to 2019 per William H. Frey analysis of census population estimates released June 25, 2020). Progress is reflected in higher rates of increase in racial/ ethnic minority groups and comparable survival across the racial ethnic groups in our cohort as compared to two prior registry studies (Baker et al. JCO 2005 and Baker et al. BBMT 2009) for most HCT patients. However, in pediatric patients undergoing allo HCT, the gap in survival between NHWs and AAs has continued to persist over the years. With increasing diversity of the US population, we need to strengthen our efforts for improving access to, and outcomes of HCT to narrow the gap for all patients requiring HCT, irrespective of their sociodemographic characteristics. [Display omitted] DisclosuresWood: Koneksa Health: Consultancy, Current equity holder in publicly-traded company; Teladoc: Consultancy; Pfizer: Research Funding. Ailawadhi: Karyopharm: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Takeda: Consultancy; GSK: Consultancy, Research Funding; Xencor: Research Funding; Cellectar: Research Funding; Medimmune: Research Funding; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; BeiGene, Ltd.: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy. Saber: Govt. COI: Other.

Immune Recovery Following Autologous Hematopoietic Stem Cell Transplantation in HIV-Related Lymphoma Patients on the BMT CTN 0803/AMC 071 Trial.

We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.

Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach.

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug–drug interactions with novel targeted therapies. This is a retrospective, single-center cohort study of consecutive cases of proven or probable IFD, diagnosed between 2009 and 2019, in adult hematologic patients and HCT recipients managed with fluconazole prophylaxis and an antifungal diagnostic-driven approach for mold infection. During the study period, 94 cases of IFD occurred among 664 hematologic patients and 316 HCT recipients. The frequency among patients with allogeneic HCT, autologous HCT, acute leukemia and other hematologic malignancies was 8.9%, 1.6%, 17.3%, and 6.4%, respectively. Aspergillosis was the leading IFD (53.2%), followed by fusariosis (18.1%), candidiasis (10.6%), and cryptococcosis (8.5%). The overall 6-week mortality rate was 37.2%, and varied according to the host and the etiology of IFD, from 28% in aspergillosis to 52.9% in fusariosis. Although IFD occurred frequently in our cohort of patients managed with an antifungal diagnostic driven approach, mortality rates were comparable to other studies. In the face of challenges posed by the use of anti-mold prophylaxis, this strategy remains a reasonable alternative.

Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients.

A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200mg/m2) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.

Catheter-Related Thrombosis in Patients with Lymphoma or Myeloma Undergoing Autologous Stem Cell Transplantation

Background: Catheter-related thrombosis (CRT) occurs frequently during autologous hematopoietic cell transplantation (AHCT) and its current management is highly variable. There is limited data regarding the incidence, risk factors, management patterns and outcomes of CRT in patients with lymphoma or myeloma undergoing AHCT.Methods: In a retrospective observational study with nested case-control risk factor analysis, we examined 789 patients with lymphoma and myeloma who underwent AHCT at University of Minnesota between 2006-2016. We identified 50 subjects with CRT from central venous catheters (CVCs). Patient and transplant characteristics and outcomes were compared in the case-control analysis with 2:1 matching by patient age and disease. All AHCT recipients underwent insertion of tunneled 14.5fr double lumen large bore tunneled catheters for hematopoietic cell apheresis. All patients underwent routine CT chest prior to AHCT and at days 28 and 100 post-transplant. The primary objective was to describe the CRT incidence, management and complications. Secondary objective was to identify CRT risk factors. Statistical comparison of categorical variables was performed by χ2 and Wilcoxon rank-sum test was used for assessment of continuous variables between cases and controls.Results: The incidence of CRT in patients with lymphoma and myeloma undergoing AHCT over the ten-year period was 6.3% (n=50); with 32% symptomatic. Out of 50 cases, 43 occurred within 100 days of AHCT and 94% cases were associated with tunneled line; predominantly internal jugular (90%). CRT was diagnosed between 21 days prior to 26 days after CVC insertion. Five patients had pulmonary embolism detected incidentally by CT imaging; all were asymptomatic. The median time from tunneled line placement to CRT was 44 days (11-89 days) Of the 50 patients with CRT, 22% had refractory Hodgkin's lymphoma (incidence in HL 11.0%), 62% non-Hodgkin's lymphoma (incidence in NHL 10.1%) and 16% myeloma (incidence in MM 2.1%). The median age at the time of CRT was 56.6 years; 60% were male. Prior radiation to chest/neck (18%), bulky mediastinal mass (12%), splenectomy (6%), bacteremia (18%), hormonal therapy (8%), and prior VTE (16%) were common amongst CRT cases. Half of CRT cases had a Port-a-cath and 46% had more than one CVC inserted peritransplant. Vein occlusion was complete in 46% and occurred with the same frequency on left and right (44% vs 42%). At the time of CRT, median platelet count was 133 (range 31-426 x 109/L). Median time of tunneled line removal was 0 days (ie. on same day as CRT) but ranged from 21 days before CRT to 161 days after CRT.Most (86%) CRTs were treated with low molecular weight heparin (LMWH) and 56% received subsequent warfarin. Only 2% were treated with unfractionated heparin. LMWH at dose 1 mg/kg twice daily was administered if platelet count could be maintained above 50 x 109/L and median time to platelet recovery was 15 days (range 9-36). Patients were anticoagulated for <3 months (38%), 3-6 months (24%), and >6 months (22%). One patient required lytic therapy for CRT. Only two patients (4%) received secondary prophylactic anticoagulation after AHCT. This management was safe and effective and grade 1-2 bleeding events occurred in only two patients (4%) during anticoagulation. Five patients (10%) had CRT recurrence or extension while 12% had subsequent VTE after CRT. No deaths occurred due to CRT or its treatment.In univariate analysis, risk factors for CRT included prior VTE event (20.9% vs 7.0%, p=0.02) and higher WBC peak at mobilization (43.5 vs 40.4 x 109/L, p=0.17) and stem cell engraftment (15.2 vs 11.9 x 109/L, p=0.18). Gender, presence of Port-a-cath, comorbidity index and Karnofsky score did not increase the risk of CRT. Two-year progression-free survival of entire group was 54% (95% CI 50-57%) and was not affected by CRT (p=0.42).Conclusions: The diagnosis of CRT complicates AHCT and appears to be more common in patients with lymphoma than myeloma. Prior VTE is the main risk factor for CRT. Anticoagulation with LMWH or warfarin appeared safe , however many patients had recurrent VTE events. Higher WBC seems to be associated with risk of thrombosis. Further study to define additional risk factors and examine the management strategies is warranted. DisclosuresBachanova:Seattle-Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Zymogen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oxis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Conditional Long-Term Survival Among Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Autologous Hematopoietic Cell Transplantation (AHCT)

Introduction: AHCT is standard therapy for chemosensitive relapsed DLBCL and survival from the time of AHCT has been well described in large patient cohorts. Outcomes have not been well described for patients who survive a certain time period after transplantation, when the risks of relapse have diminished. We performed a retrospective cohort study to delineate conditional survival in patients with DLBCL who survived 1, 2, and 5 yrs after AHCT. We also compare survival for these cohorts to their general population controls.Methods: We included 371 consecutive adult (≥18 yrs) patients with DLBCL who received AHCT at our institution from 2000-2014. 10-year overall survival (OS), progression-free survival (PFS), relapse mortality (RM) and non-relapse mortality (NRM) from AHCT were determined for three cohorts: 1-yr survivors (N=272), 2-yr survivors (N=232), and 5-yr survivors (N=157). Outcomes were estimated with Kaplan-Meier (OS, PFS) or cumulative incidence (RM, NRM). Cox regression analyses were performed to evaluate prognostic factors for OS and PFS. In addition, standardized mortality ratio (SMR) compared to the age-, gender- and race-matched healthy population was estimated for each survivor cohort.Results: Median age for 1-yr cohort was 56 yrs (19-78 yrs). 61% were male, 78% were stage III/IV and 45% had B-symptoms at diagnosis, 28% had received prior radiation and 81% had received prior rituximab. 77% patients received chemotherapy mobilization and Bu/Cy/VP was conditioning regimen for 97% patients. Median followup for this 1 yr cohort was 8 yrs (1.3-16.5 yrs). OS, PFS, RM and NRM at 10 yrs after AHCT are described in Table 1. OS and PFS improved with increasing survival after transplantation. Relapse was the primary cause of death in 1- and 2-yr survivors; cumulative incidence of RM and NRM was low but similar in 5-yr survivors. As expected, in multivariable analyses, lymphoma relapse prior to landmark time was associated with significantly worse OS and PFS for 1-, 2- and 5-yr survivors. Among other patient and disease characteristics evaluated in risk factor analysis, age and duration of AHCT hospitalization were the only factors associated with OS and PFS. Older age (10 yr increments) was associated with greater mortality risk among 1- and 2-yr but not 5-yr survivors. Older age at AHCT was associated with worse PFS in all three survivor cohorts. Prolonged hospital stay, as a surrogate for early post-transplant complications, was also associated with lower OS for all three cohorts, and lower PFS for 2-yr and 5-yr survivors. Survival was lower compared to the general population, although it improved and approached that of healthy peers with increasing post-transplant survival (SMR 4.0, 3.0 and 1.8 among 1-, 2- and 5-yr survivors, respectively, Figure 1).Conclusions: Conditional OS and PFS for DLBCL patients treated with AHCT improves with increasing survival post-transplantation. Relapse is the primary driver of poor survival, although the probability of death due to relapse decreases over time. NRM continues to be an important cause of treatment failure even among patients surviving 5-years after AHCT. Our data provide personalized survivorship information for DLBCL AHCT recipients and identify risk factors for poor survival. Our study also underscores the need for continued research on decreasing relapse risk and for surveillance for prevention and management of late-complications in this population. [Display omitted] DisclosuresKharfan-Dabaja:Incyte: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Seattle Genetics: Speakers Bureau. Majhail:Anthem, Inc.: Consultancy; Sanofi: Honoraria.