Auto Hematopoietic Cell Transplantation Research Articles

Comparing Survival Outcomes of Autologous and Allogeneic Hematopoietic Cell Transplantation in Patients with Relapsed/Refractory Nodal Peripheral T-Cell Lymphoma

Background Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma and carries a poor prognosis. The four most common types are PTCL-NOS, angioimmunoblastic T cell lymphoma (AITL), and anaplastic large T cell lymphoma (ALCL) with or without ALK and together are grouped as nodal PTCL. In relapsed/refractory disease (r/r), the survival outcomes are poor and estimated to be approximately 13.7 months (Mak, Hamm et al. 2013). Hematopoietic cell transplantation (HCT) has been used to consolidate response and improve outcomes. However, the role of autologous HCT (auto HCT) and allogeneic HCT (allo HCT) remains controversial. Here we aim to compare the survival outcomes of auto HCT and allo HSCT in r/r PTCL. Methods We retrospectively reviewed clinical data on 53 patients at Moffitt Cancer Center who developed r/r nodal PTCL and received HCT from 12/2007 to 12/2021. Patients who had auto HCT during the first remission were excluded. Physician discretion, donor availability, among others, were the factors that influenced transplant type allocation. Clinical data were abstracted in accordance with institutional review board-approved protocol. Patients were divided into two subgroups: cohort A) auto HCT and cohort B) allo HCT. The baseline clinical data of two cohorts were summarized using descriptive statistics and compared using Kruskal-Wallis tests for continuous variables and Chi-squared tests for categorical variables. Overall survival (OS) was calculated from the date of HCT to death or censored to the last follow-up. Median OS was calculated using the Kaplan Meier method and compared two cohorts with a log-rank test. Univariate and multivariate Cox proportional hazard (PH) using the backward elimination method were used to evaluate the association between OS and types of transplants. Results Out of 53 patients, 30 (57%) patients received auto HCT (cohort A), while 23 (43%) patients received allo HCT (cohort B). All patients achieved either partial response (PR) or complete response (CR) prior to transplant. The patients in allo cohort B were younger at the time of transplant (median age: 60 years vs. 50 years for cohort A and B, respectively, p=0.06), had a higher proportion of refractory disease (27% vs. 65% for cohort A and B, respectively, p=0.005), and had a higher proportion of PTCL-NOS (33% vs. 65% for cohort A and B, respectively, p=0.006) (table 1). ECOG status at transplant and IPI at the time of diagnosis were not significantly different between the two groups. Median OS was 40 months in cohort A compared to 57 months in cohort B, however, no statistical difference was present (p=0.49) (Figure 1). In the univariate analysis, HR for allo HCT was 0.77 (p=0.5). When adjusted for ECOG status at transplant, histology subtypes, IPI score at diagnosis in the multivariate analysis, allo HCT was associated with prolonged OS with an HR of 0.41 (p=0.045). At the study cutoff with a median follow-up of 57 months in cohort A, 18 patients died. Out of 12 patients with a known cause of death in cohort A, 7 patients (38%) died from relapse disease. With a median follow-up of 73 months in cohort B, 10 patients died. Out of 10 patients with a known cause of death, 2 patients (20%) died from the relapsed disease. Conclusion Our data showed that allo HCT in r/r PTCL is associated with improved survival compared to auto HCT in multivariate analysis. Our result supports the use of allo HCT, especially in the younger/fit population and in refractory disease. Larger studies are needed to validate our results. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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.

COVID-19 in Pediatric Hematopoietic Cell Transplant Recipients: A CIBMTR Study

Background: Adult recipients of hematopoietic cell transplantation (HCT) are at a very high risk of adverse outcomes after COVID-19 (Sharma A, Bhatt NS, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. The Lancet Haematology. 2021 Mar 1;8(3): e185-93). While children are known to have better outcomes after COVID-19 compared to adults in general, data on risk factors and outcomes of COVID-19 among pediatric recipients of HCT are lacking.Methods: Using the data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between March 2020 and May 2021, we describe characteristics, severity, treatment approaches, and outcomes of pediatric HCT recipients who were ≤21 years of age at COVID-19 diagnosis. All diagnoses, donor choice/graft sources, and conditioning regimens were included. Patient, disease, and HCT-related factors were described as frequency for categorical variables and median, range, and interquartile range (IQR) for continuous variables. The probability of overall survival after COVID-19 was calculated using the Kaplan Meier estimator. Additionally, an analysis was performed in the subset of allogeneic HCT COVID-19 cases from the United States (US) to identify risk factors for developing COVID-19. COVID-19 cases were compared with a cohort of all pediatric allogeneic HCT recipients without COVID-19 matched by the transplant center. Impact of hematopoietic cell transplant comorbidity index (HCT-CI), HCT indication, donor type, conditioning intensity, graft vs. host disease (GVHD) prophylaxis, and occurrence of acute and chronic GVHD on development of COVID-19 was examined using Cox proportional hazards model. Hazard ratio (HR) and 95% confidence intervals (CI) were provided. Cumulative incidence of COVID-19 among the US centers reporting at least 1 COVID-19 infection was also calculated, using death from any cause as a competing risk. P value <0.05 was considered statistically significant for the analyses.Results: A total of 167 pediatric HCT recipients (allogeneic, allo: 135 and autologous, auto: 32) met study inclusion criteria. Median age at COVID-19 diagnosis for allo and auto HCT recipients were 15 years (range <1-21y) and 7 years (range 1-21y), respectively. Median time from HCT to COVID-19 diagnosis was 15 months (IQR 7-45) for allo recipients and 16 months (IQR 6-59) for auto HCT recipients. Forty-two percent (42%) of the patients had at least one comorbidity prior to HCT. Thirteen percent (13%) were receiving immunosuppression within six months prior to COVID-19 diagnosis. COVID-19 disease severity was mild in 87% of patients, while 4% of patients had severe disease requiring mechanical ventilation or supplemental oxygen. Only 36 HCT recipients (22%) received any COVID-19 directed therapy. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (range 1-179) for allo and auto HCT recipients, respectively. The overall probability of survival at 45 days was 95% (95% CI 90-99%) and 90% (95% CI 74-99%) for allo and auto HCT recipients, respectively (Figure 1). Forty-five (45) day survival was lower among recipients transplanted at the transplant centers outside the US [non-US recipients 85% (95% CI 71-95%) versus US recipients 98% (95% CI 93-99%)]. No deaths occurred in patients who had received a transplant between 2000-2013. The primary cause of death was COVID-19 in 54% of patients and primary disease in 38% of patients. In the subset analysis restricted to pediatric allogeneic HCT recipients transplanted at the US centers (n=34), the cumulative incidence of COVID-19 infection was noted to be 1.9% (95% CI 1.2-2.9%) at 6 months post-HCT and increased to 4.7% (95% CI 3.4-6.3%) by 1-year post-HCT. Cox regression analysis showed that compared to HCT-CI score of 0, patients with HCT-CI score of 1-2 were more likely to develop COVID-19 (HR 1.95; 95% CI 1.03-3.69, p=0.042). Underlying diagnosis, donor type, treatment exposures, or GVHD did not predict COVID-19 incidence.Conclusions: This is the largest series to date summarizing the cumulative incidence, risk factors, and outcomes of pediatric HCT recipients with COVID-19. Patients with pre-HCT comorbidities were more likely to develop COVID-19. However, the overall disease severity and mortality after COVID-19 were low in this patient cohort. [Display omitted] DisclosuresBhatt: Rite Aid Corporation: Divested equity in a private or publicly-traded company in the past 24 months; Pfizer Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Moderna, Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months. Sharma: Medexus Inc: Consultancy; Spotlight Therapeutics: Consultancy; Vindico Medical Education: Honoraria; CRISPR Therapeutics: Other, Research Funding; Novartis: Other: Salary support paid to institution; Vertex Pharmaceuticals/CRISPR Therapeutics: Other: Salary support paid to institution. Riches: ATARA Biotherapeutics: Other: Payment; Jazz Pharmaceuticals: Other: Payment; BioIntelect: Membership on an entity's Board of Directors or advisory committees. Dandoy: Omeros: Other: Consulted and received Honorarium.

Cost of HSCT in a Tertiary Care Public Sector Hospital in India.

India harbours a significant burden of hematological diseases including cancers for which Hematopoietic Cell Transplant (HCT) is a definitive life-saving procedure. Very few studies in India have carried out the costing of the important procedure, hence we undertook a study to ascertain the cost of auto HCT in our tertiary care teaching hospital. We did a prospective study using Top-down and Bottom-up approach to arrive at the cost of autologous HCT which came out to be INR 699,200 ($10,282) out of which hospital bears 34% of the cost. The major share of the hospital cost is on account of expenditure on Human Resources. The rest 66% is Out of Pocket Expenditure (OOPE) for the patients. We also calculated the cost which is borne by patient attendants over & above the cost of procedure while caring for the patient, which on an average came to be INR 88,598. This is approximately 19% of the cost borne by the patient for the procedure itself. The cost is usually not factored in while contemplating the procedure and is not covered by any insurance scheme. The overall cost, OOPE & attendant cost can all lead to a substantial financial hardship. Hence, steps need to be taken to make HCT an affordable and accessible procedure.

Comparison of Reduced Intensity Conditioning - Allogeneic HCT and Autologous HCT for Elderly Patients with Acute Lymphoblastic Leukemia. an Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

BACKGROUND: The outcome of patients with acute lymphoblastic leukemia (ALL) aged above 55 years treated with conventional-dose chemotherapy is poor. Due to the frequent presence of co-morbidities many patients are ineligible for myeloablative allogeneic (allo) hematopoietic cell transplantation (HCT). The role of autologous (auto) HCT and reduced intensity conditioning (RIC)-alloHCT is not well-established. The goal of this study was to analyze results of these transplant options and to identify factors affecting outcome. PATIENTS: Five-hundred and sixty patients with ALL treated in first complete remission (CR1) with RIC-alloHCT (n=418) or autoHSCT (n=142), between 2000-2018, were included in the analysis. Among allogeneic donors, 50% were HLA-matched sibling donors (MSD) and 50% were 8/8 HLA matched unrelated donors (MUD). Median age for RIC-alloHCT and autoHCT was 60 (range 55-76) years and 61 (range 55-76) years, respectively. The proportion of Philadelphia chromosome positive (Ph(+)) ALL was 71% and 63%, respectively. Measurable residual disease (MRD)-positive status at the time of HCT was reported in 35% and 21% patients, respectively (p=0.002). Busulphan and fludarabine (BuFlu) was the most frequently used conditioning regimen in the RIC-alloHCT setting (34%) while a combination of 12 Gy total body irradiation/cyclophosphamide (TBI12Gy/Cy) was most frequent in the autoHCT group (33%). RESULTS: The engraftment rate was 99% after RIC-alloHCT and 96% after autoHCT (p=0.01) while median time to neutrophil recovery was 16 days and 12 days, respectively (p&amp;lt;0.001), respectively. With a median follow-up of 57 months, the probabilities of leukemia-free survival (LFS) and overall survival (OS) at 5 years were 39% versus 34% (p=0.11) and 45% vs. 42% (p=0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) were 41% vs. 51% (p=0.22) and 25% vs. 10% (p=0.001), respectively. In a multivariate model, using autoHCT as reference, the risk of NRM was increased for MSD-HCT (HR=2.1, p=0.02) and MUD-HCT (HR=3.08, p&amp;lt;0.001), which for MUD-HCT translated into a decreased chance of LFS (HR=1.55, p=0.01) and OS (HR=1.62, p=0.008). For MSD-HCT there was a tendency towards decreased LFS (HR=1.31, p=0.11) and OS (1.29, p=0.15) when compared to autoHCT. Among other prognostic factors, the risk of relapse was decreased for Ph(+) ALL compared to Ph(-) B-ALL (HR=0.7, p=0.04) which was accompanied by improved OS (HR=0.74, p=0.04). Finally, the risk of relapse was increased for patients with detectable MRD (HR=1.38, p=0.04) without significant effect on survival. CONCLUSIONS: Results of autoHCT for patients with ALL aged above 55 years in CR1 and with MRD negativity pre-transplant are encouraging. This option may be a valuable alternative to RIC-alloHCT and is associated with an improved OS compared to transplantations from MUD. Our observations require verification in prospective trials in the context of currently available novel agents and technologies, including blinatumomab, inotuzumab ozogamicin and CAR-T cells. Figure. Results of RIC-alloHCT and autoHCT for patients with ALL in CR1 aged &amp;gt;55 years Figure Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria. Forcade:Novartis: Other: Travel grant for congress; Sanofi: Other: Travel grant for congress; JAZZ: Other: Travel grant for congress; NEOVII: Other: Travel grant for congress; Gilead: Speakers Bureau. Yakoub-Agha:Janssen: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Novartis: Honoraria; Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria. Mohty:Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Safety and Demonstrated Efficacy of Placenta-Derived Cell Therapy PLX-R18 in Subjects with Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation: A Phase I International Multi-Center Study

Introduction: Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT) while full engraftment remains a challenge in some recipients. Therapeutic approaches, such as recombinant hematopoietic growth factors, salvage only a minority of patients leaving affected patients at risk for recurrent infections and multiple blood products transfusions. PLX-R18 cells have been shown to mitigate bone marrow failure in rodent and non-human primate models. Further, these human placenta-derived mesenchymal-like adherent stromal cells secrete many cytokines after intramuscular (IM) injection that have been shown to stimulate growth and migration of bone marrow cells in vitro, e.g. MCP-1, IL-6, and IL-8. The initial results of the first cohort of this phase I trial were previously reported (ASH 2018 abstract 3379). Methods: Enrollment for this multi-center, open label, dose-escalation, phase I trial (ClinicalTrials.gov: NCT03002519) began in October 2017. Eligibility criteria included patients age ≥18 years who underwent either autologous (auto) or allogeneic (allo) HCT but suffered from incomplete hematopoietic recovery at least 3 months post-transplant, defined as failure to maintain either hemoglobin (Hb) &amp;gt;8g/dL and/or neutrophil count (ANC) &amp;gt;1,000/μL and/or platelet (PLT) count &amp;gt;50,000/μL. Other eligibility criteria included no evidence of underlying malignancy at time of enrollment, no active infection and no evidence of grade 3-4 acute or severe chronic GvHD. Subjects were enrolled into 3 dose-escalating cohorts: low-dose at 1M cells/kg (n=3), intermediate-dose at 2M cells/kg (n=6), and high-dose at 4M cells/kg (n=10). The specified dose of PLX-R18 cells was injected IM in multiple locations and given twice, 1 week apart. Cohorts were recruited sequentially, and progression to the next cohort was based on the safety assessment of its predecessor. Adverse event grading used the NCI CTCAE criteria. As of July 2020, all patients in cohorts 1 and 2 (3 &amp; 6 patients, respectively) and 10 patients in cohort 3 were treated. Data were analyzed using the lmerTest package (ver. 3.1.0) in R (ver. 3.6.1) to produce baseline-adjusted least square means. As study is in progress and data collection ongoing, not all subjects have data on all parameters for all time points. Results: Data on 19 subjects (29-75 yrs) with either allo (n=17) or auto (n=2) HCT are reported herein. Not all patients reached the 9 month time point. Four patients died while on study and 2 withdrew consent within the 1 year follow up period. All deaths and other severe adverse events (SAEs) occurred due to progression of primary disease and were assessed as not related by investigators and sponsor. Most frequent related AEs were injection-site reactions. The table summarizes number of patients who improved from below the critical level, as defined above, at day 0 to above the critical level for a sustained period. Only those patients that were below the critical blood levels at day 0 are shown. To date, the majority of such patients improved to above the critical level after treatment. For example, 9 patients had ANC &amp;lt;1000/μL at day 0. Of the 4 patients for which data currently exists, all improved to ≥1000/μL at 9 months. The plots show changes in Hb, ANC and PLT up to 9 months following treatment. The dashed lines represent respective critical levels. Overall, there was improvement in the 3 parameters, with the greatest improvement observed in patients receiving the predicted optimal dose of 4M cells/kg. In this cohort, Hb levels increased from 9.29±0.5 to 13.19±1.2 (p=0.0019), ANC increased from 1.09±0.6 to 5.13±1.7 (p=0.018) and PLT increased from 45.7±10 to 175.9±28 (p=0.000012). Conclusions: Treatment with PLX-R18 is safe, well-tolerated and clearly effective in some patients. The most frequent AEs were reversible injection site reactions, all without sequelae. An overall improvement was observed in most patients, and among the high-dose cohort clinically impressive improvements in Hb, ANC and PLT were observed. The trial continues to follow up on patients. Upon completion, a large phase II trial, using the optimal dose, is considered for the same indication. Other attractive clinical areas for PLX-R18 therapy include acute radiation syndrome, bone marrow failure, aplastic anemia, myelofibrosis and with HCT as a "pan" cytokine to enhance rapid count recovery in all cells lines. Figure Disclosures Lazarus: Pluristem ltd: Consultancy. McGuirk:Astellas: Research Funding; Bellicum Pharmaceutical: Research Funding; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Rowley:AbbVie: Current equity holder in publicly-traded company; FATE Therapeutics: Consultancy. Ofir:Pluristem: Current Employment. Shani:Pluristem ltd: Current Employment. Rowe:Pluristem ltd: Consultancy.

Outcomes of Hematopoietic Cell Transplantation in Acute Promyelocytic Leukemia – a Single Institution Experience

<h3>Background</h3> Outcomes of patients with acute promyelocytic leukemia (APL) have improved; however, a significant number of patients still relapse despite receiving all-trans-retinoic acid (ATRA) and arsenic-based therapies. We present single institution outcomes of autologous (auto) and allogenic (allo) hematopoietic cell transplantation (HCT) in patients with relapsed APL. <h3>Methods</h3> Outcomes in patients with relapsed APL who underwent either auto- or allo- HCT at Moffitt Cancer Center from 1990 to 2018 were reviewed utilizing the clinical data obtained from BMT Research & Analysis Information Network (BRAIN). Survival data were analyzed using Kaplan-Meier estimates. <h3>Results</h3> <b>Autologous HCT Cohort:</b> A total of 15 received auto-HCT with a median age at HCT of 39 (range, 21-60) years. Only 3/8 patients with known disease risk at time of diagnosis had high risk disease (high=3, low=5). Disease status at HCT were first complete remission (CR1) in 5 (33%) and CR2 in 10 (67%). All 8 patients who had minimal residual disease evaluation had negative PCR for PML-RARA. The median progression-free survival (PFS) for auto HCT was 12.9 (95% confidence interval (CI): 1.2-24.8) years. With a median follow up of 45.1 months for surviving patients, overall survival (OS) for auto HCT was 12.9 (95%CI: 0-27.8) years. <h3>Allogeneic HCT Cohort</h3> A total of 9 patients received allo HCT with a median age at HCT of 43 (range, 22-56) years. All six patients with known disease risk at time of diagnosis were either intermediate (n=2) or high risk disease (n=4). Disease status at allo HCT was CR2 in 1, CR3 in 6, and two had refractory disease. Two patients had prior auto HCT. 5/6 patients who had minimal residual disease evaluation had negative PCR for PML-RARA. Donor type was HLA-identical sibling=5; one antigen-mismatched sibling=1; HLA-matched unrelated donor=2; related haploidentical=1. Conditioning regimen intensity was myeloablative in six and reduced intensity in three of the patients. Six patients received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. The median PFS for allo HCT was 11.9 (95%CI: 0-24.1) months. With a median follow up of 48.2 months for surviving patients, OS for allo HCT was 14.2 (95%CI: 6.5-21.9) months. <h3>Conclusions</h3> In our single center analysis, auto HCT resulted in a durable remission and prolonged survival. Outcomes after allo HCT were suboptimal primarily due to their heavily pretreated condition and chemotherapy resistant disease.

Burden of Vaccine-Preventable Infections Among Pediatric Hematopoietic Cell Transplant Recipients

<h3>Background</h3> Hematopoietic cell transplantation (HCT) recipients are increased risk for vaccine-preventable infections (VPI). However, the true prevalence of VPI in children post-HCT is unknown. <h3>Methods</h3> We performed an epidemiological study using the Pediatric Health Information System (PHIS) database in children and young adults who underwent allogeneic (allo) and autologous (auto) HCT and had a first hospitalization with a VPI (as defined by ICD-9 and ICD-10 codes) within 5-yr post-HCT between Jan 1, 2010 and Dec 31, 2018 at the 45 participating US PHIS hospitals. Prevalence for overall VPI and by infection were calculated at the following timepoints: at initial HCT admission, HCT discharge to D100, D101-D180, 6-12 months, 1-2 yr, and 2-5 yr post-HCT. <h3>Results</h3> We identified 9,591 unique HCT recipients (alloHCT: 6,602, 69%; autoHCT: 2,989, 31%) with a median age of 6.7 years (range infant-18.9 yrs) during the 8-yr study period. Of these, 684 HCT recipients (510 alloHCT, 174 autoHCT) were hospitalized with VPI in the first 5 yrs after HCT, for an overall prevalence of 7.1%. VPI occurred more frequently among alloHCT (8%) than autoHCT recipients (6%) at all time-points (p=0.0008). VPI hospitalizations occurred a median of 221 days post-HCT [range 0-5 yrs] with the majority occurring in the first 6-12 mos post-HCT (Figure 1). Influenza was the most frequent VPI (4.05%) (Table I). <h3>Conclusion</h3> The overall prevalence of VPI hospitalizations after pediatric HCT was 7.1%, occurring most frequently in the first 6-12 months post HCT and among alloHCT recipients. Continued efforts to prevent VPI, including optimizing vaccination strategies in this population, are warranted.

Outcomes of Hematopoietic Cell Transplantation in Acute Promyelocytic Leukemia - a Single Institution Experience

BACKGROUND: Outcomes of patients with acute promyelocytic leukemia (APL) have improved; however, a number of patients, particularly those with high-risk APL, still relapse despite all-trans-retinoic acid (ATRA) and arsenic-based therapies. We present single institution outcomes of autologous (auto) and allogenic (allo) hematopoietic cell transplantation (HCT) in patients with relapsed APL. PATIENTS AND METHODS: We retrospectively reviewed outcomes in patients with relapsed APL who underwent either auto- or allo- HCT at Moffitt Cancer Center from 1990 to 2018 utilizing the clinical data obtained from BMT Research &amp; Analysis Information Network (BRAIN). Survival data were analyzed using Kaplan-Meier estimates. RESULTS: Autologous HCT Cohort: A total of 15 received auto-HCT with a median age at HCT of 39 (range, 21-60) years. Disease status at HCT were first complete remission (CR1) in 5 (33%) and CR2 in 10 (67%). Majority of patients (13/15, 87%) received busulfan/cyclophosphamide (Bu/Cy) conditioning and remaining (2/15, 13%) Bu/Cy/etoposide. All (n=15) patients received peripheral blood (PB) stem cell grafts. Median time to neutrophil engraftment was 11 (range, 10-14) days and platelet recovery was 14 (range 9-44) days. The median progression-free survival (PFS) for auto HCT was 12.9 (95% confidence interval (CI): 1.2-24.8) months. With a median follow up of 45.1 months for surviving patients, overall survival (OS) for auto HCT was 12.9 (95%CI: 0-27.8) years. At the time analysis, 8 patients were relapse-free. Allogeneic HCT Cohort: A total of 10 patients received allo HCT with a median age of 46 (range, 22-56) years at HCT. Disease status at allo HCT was CR2 in 2, CR3 in 6, and two had refractory disease. Two patients had prior auto HCT. Donor type was HLA-identical sibling=5; one antigen-mismatched sibling=1; HLA-matched unrelated donor=3; related haploidentical=1. Seven patients received peripheral blood graft and 3 received bone marrow graft. Conditioning regimen intensity was myeloablative in 7 (fludarabine/busulfan +/- anti-thymocyte globulin=3; Bu/Cy=3; cyclophosphamide/total body irradiation=1), and reduced intensity in 3 (fludarabine/melphalan=2; fludarabine/cyclophosphamide/total body irradiation=1). Seven patients received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. Median time of neutrophil engraftment was 15 (range, 12-22) days, and platelet engraftment was 22 (range, 15-28) days. The median PFS for allo HCT was 11.9 (95%CI: 2.1-21.6) months. With a median follow up of 48.2 months for surviving patients, median OS for allo HCT was 12.4 (95%CI: 4.8-19.9) months. At the time of analysis 4 patients were relapse-free. CONCLUSIONS: In our single center analysis, auto HCT for APL resulted in a durable remission and prolonged survival. Outcomes after allo HCT were suboptimal primarily due to their heavily pretreated condition and chemotherapy resistant disease. Further research on novel conditioning regimen and relapse prevention is needed to improve the outcomes of allo HCT in APL. Figure Disclosures Lancet: Jazz Pharmaceuticals: Consultancy; Agios Pharmaceuticals: Consultancy; Daiichi-Sankyo: Consultancy; Pfizer: Consultancy. Sweet:Pfizer: Consultancy; Celgene: Speakers Bureau; Jazz: Speakers Bureau; Incyte: Research Funding; Stemline: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Komrokji:JAZZ: Speakers Bureau; Novartis: Speakers Bureau; Agios: Consultancy; JAZZ: Consultancy; Incyte: Consultancy; pfizer: Consultancy; DSI: Consultancy; celgene: Consultancy. Bejanyan:Kiadis Pharma: Other: advisory board. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding.

A Retrospective Validation of Three Standard Prognostic Instruments Used to Inform Decisions Regarding Autologous and Allogeneic Stem Cell Transplantation

Background The Hematopoietic Cell Transplantation (HCT) – Specific Comorbidity Index (HCT-CI) measures the risk of transplant related mortality and predicts overall survival (OS) based on co-morbidities. In a prospective validation study of the HCT-CI by the Center for International Blood and Marrow Transplant Research (CIBMTR), HCT-CI ≥ 3 was associated with lower OS in both allogeneic (allo) and autologous (auto) HCT regardless of diagnoses, age, or conditioning. In contrast to the patients (pts) analyzed in the CIBMTR study, pts transplanted at Wake Forest more often have HCT ≥3. Methods We retrospectively analyzed data from pts transplanted from Sep 2014 to Sep 2016. 2-yr OS was observed for all pts. Results from 3 tools were used to compare predicted vs observed OS: HCT-CI, Disease Risk Index (DRI), and the CIBMTR survival calculator. Results Over 2 yrs, 216 pts were transplanted – 132 auto, median age 62 (26-78) and 84 allo, median age 55.5 (16-74). 59% of pts had a HCT-CI ≥3. In both groups, predicted and observed OS were not statistically different for those with HCT-CI 0. In contrast, predicted and observed OS for HCT-CI ≥3 were significantly different (p Conclusions Compared to the dataset utilized by the CIBMTR for validation of the HCT-CI, scores ≥ 3, largely accounted for by poor pulmonary function, are over represented in our population. Further analysis will need to be done to determine if the regional prevalence of poor pulmonary function is contributing to a significant difference in the predicted vs observed OS in our allo pts.

Late Effects of CD19-Targeted CAR-T Cell Therapy

Recently two CD19-targeted CAR-T cell products were approved by the FDA for treatment of relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Excellent anti-tumor activity has been observed in patients with B cell malignancies. However, data regarding long-term effects of this therapy are very limited.Here we report long-term effects in 59 patients (pts) with R/R NHL and chronic lymphocytic leukemia (CLL) who received a total of 85 CD19-targeted CAR-T cell infusions on a clinical trial in our institution (NCT01865617), survived more than a year, and had at least one year follow-up data after their first CAR-T cell infusion. One patient who survived more than a year was excluded from this report due to incomplete data. Median follow-up was 23 months (range, 13-57) after the first CAR-T cell infusion. We report adverse events that occurred or persisted beyond 90 days after the last CAR-T cell infusion, excluding events related to disease progression.Median age at CAR-T cell infusion was 60 years (range, 34-73). There were 42 (71%) pts with NHL and 17 (29%) with CLL. The median number of prior lines of treatment was 4 (range, 1-8). 23 (39%) pts had received prior autologous (auto) hematopoietic cell transplantation (HCT), and 9 (15%) pts had received prior allogeneic (allo) HCT. 35 (59%) pts received one CAR-T cell infusion, 22 (37%) pts received 2 infusions, and 2 (3%) pts received 3 infusions. 3 (5%) pts received a maximum cell dose of 2x10(5)/kg, 40 (68%) pts received a maximum cell dose of 2x10(6)/kg, and 16 (27%) pts received a maximum cell dose of 2x10(7)/kg. 65 (76%) infusions were preceded by cyclophosphamide and fludarabine. CRS grade I/II occurred in 38 (64%) pts, and grade III in 4 (7%) pts (graded per Lee et al. Blood, 2014). No grade IV CRS was reported in this cohort. Acute neurotoxicity occurred in 20 (34%) pts.At 2 months after CAR-T cell infusion complete response (CR) was documented in 34 (58%) pts, partial response (PR) in 12 (20%) pts, and disease progression (PD) in 13 (22%) pts. During the follow-up period, another 15 (25%) pts developed PD. 29 (49%) pts received salvage therapy after CAR-T cell infusion, 8 (14%) of them received allo HCT. 5 (8%) pts received allo HCT as consolidation after CAR-T cell.5 of 25 (20%) pts who did not receive additional therapy after last CAR-T cell infusion experienced ongoing cytopenias requiring G-CSF support, or RBC or platelet transfusions, beyond 90 days after last CAR-T cells infusion.8 (14%) pts were diagnosed with subsequent malignancies, including 3 (5%) myelodysplasia, 4 (7%) non-melanoma skin cancer, and 1 non-invasive bladder cancer. All, but 1 patient with skin cancer, had auto or allo HCT before CAR-T cell therapy. Neuropsychiatric disorders were documented in 5 (8%) pts; including major depression, suicidal attempt, myoclonic seizures, and TIA. 5 (8%) pts experienced cardiovascular events. 4 (7%) pts developed renal dysfunction. 3 (5%) pts developed respiratory disorders. One pt had gastrointestinal bleeding. Of the 9 pts who had undergone allo HCT before CAR-T cell therapy, 1 pt (11%) developed GVHD flare.Severe hypogammaglobulinemia (IgG < 400 mg/dL) or IgG replacement beyond day 90 after last CAR-T cell infusion (and before HCT if was done) were documented in 24 (41%) pts.54 pts were included in the infection analysis. 178 suspected infection events beyond day 90 after last CAR-T cell infusion were documented in 40 (74%) pts. Antimicrobial treatments were documented for 124 infection events. 44 (25%) of the events were microbiologically proven. The most common infections were upper (92) and lower (29) respiratory tract infections. 25 (46%) pts required hospital admission due to infections, of them 8 (15%) were admitted to the ICU. When excluding infections that occurred after salvage therapy following CAR-T cell, we identified 117 infections in 28 (52%) pts.3 pts died of non-relapse causes (2 due to infection after allo HCT, and 1 due to duodenal ulcer and gut perforation).In conclusion, our data suggest that long-term effects of CD19-targeted CAR-T cell therapy are acceptable. Most effects identified in our cohort were not severe, and many may have been related to prior or subsequent therapies (e.g. HCT before or after CAR-T cell therapy, or subsequent salvage treatments). Our data is consistent with recent published data demonstrating excellent long-term disease outcome for this heavily pre-treated population. [Display omitted] DisclosuresTurtle:Juno/Celgene: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Caribu Biosciences: Membership on an entity's Board of Directors or advisory committees. Maloney:Juno Therapeutics: Research Funding; GlaxoSmithKline: Research Funding; Janssen Scientific Affairs: Honoraria; Roche/Genentech: Honoraria; Seattle Genetics: Honoraria.

Prospective, Multi-Center, Phase I Clinical Trial of PLX-R18 Placental Expanded Adherent Stromal Cells in Subjects with Incomplete Hematopoietic Recovery after Hematopoietic Cell Transplantation

Background: Successful engraftment remains a challenge in hematopoietic cell transplantation (HCT) for some patients. Salvage approaches, including use of recombinant hematopoietic growth factors, cytokine therapy, CD34+-selected progenitor cell boosts, or second or subsequent HCT, are successful only in a minority of patients, and patients are exposed to prolonged blood products transfusions. With our successful pre-clinical rodent and Rhesus Macaques total body irradiation injury-induced marrow failure models (Metheny, Front Med 2018; Sher, Cell Transplantation 2018; Sher, Blood 2017), this prospective, multi-center, phase I clinical trial is evaluating the safety of PLX-R18 cells used to improve peripheral blood counts in patients who have experienced incomplete hematopoietic recovery after HCT. PLX-R18 cells are human placental-derived adherent stromal cells that are predominantly of fetal origin, expressing CD105, CD73 and CD29, and lacking surface expression of CD45, CD34, CD14, CD19, HLA-DR, CD31 (endothelial marker) and GlyA (erythrocyte cell marker). PLX-R18 also do not express HLA class II molecules (HLA-DP, DQ, and DR) and co-stimulatory markers (CD80, CD86, and CD40). PLX-R18 cells secrete MCP-1, IL-6, and IL-8 and had been shown to stimulate migration of bone marrow cells in vitro. Cells are grown ex vivo, under GMP conditions, using a 3-dimensional system, and are administered as several intramuscular (IM) injections. PLX-R18 cells already are approved for treatment of acute radiation syndrome (ARS) under an IND.Methods: This is a multi-center, open label, dose-escalation, phase 1 trial (ClinicalTrials.gov: NCT03002519). Eligibility criteria include patients age ≥18 years who underwent either an autologous (auto) or an allogeneic (allo) HCT but had incomplete hematopoietic recovery at 4 months post-transplant, defined as failure to maintain either hemoglobin (Hb) >8 g/dL and/ or neutrophil count (ANC) >1,000/µL and/or platelet count (Plt) (unsupported) >50,000/µL. Other eligibility criteria include ECOG performance status of 0-2, no evidence of underlying malignancy at time of enrollment, no active infection, and no evidence of grade 3-4 acute or severe chronic GvHD. The PLX-R18 cells, cryopreserved in DMSO and human serum albumin in Plasma-Lyte, are thawed and injected IM in multiple locations - half into the gluteus medius muscle on one side and half to the thigh muscles on the contralateral side. A total of 24 subjects are planned to be enrolled into 3 dose escalating cohorts: low (n=3) given 1 million cells/kg; intermediate (n=6) at 2 million cells/kg and high (n=15) dosed at 4 million cells/kg each. The assigned dose is given twice, 1 week apart; cohorts are recruited sequentially and progression to the next cohort is based on the safety assessment of its predecessor. Adverse event is graded using the CTCAE criteria of the NCI. As of July 2018, all 3 patients of cohort 1 were treated (with sufficient follow-up), as well as 3 out of the 6 subjects planned for the 2nd cohort, and data of the first cohort are presented herein.Results: Cohort 1 (low-dose) - 3 subjects (ages 43, 48 and 55 years old) who had an allo (n=2) or auto (n=1) HCT received two IM administrations of PLX-R18, 1 million cells/kg each within a 1-week interval. 67 Adverse Events (AEs) were recorded. 64.3% of the AEs were grade 1, 30.9% were grade 2, 3.6% were grade 3 and 1.2% were grade 4. One patient suffered from 3 Serious AEs (immune thrombocytopenic purpura, bacteremia and migraine), all assessed as not related to treatment. Most frequent related AE was transient injection site pain, experienced by all 3 patients. See patients' details and blood counts in the table and graphs.Conclusions: Treatment with PLX-R18 generally was well-tolerated and most frequent adverse events were injection site reactions, which were all reversible without sequelae. The trial continues to accrue patients and the next dosing cohort (intermediate dose) is at 2 million cells/kg.Upon completion, a larger phase II trial will be considered in the same indication using the optimal dose. Other potential uses include PLX-R18 therapy in Acute Radiation Syndrome, Bone marrow failure, and in HCT as a “pan” cytokine for rapid count recovery. [Display omitted] DisclosuresLazarus:Pluristem Ltd.: Consultancy. Zuckerman:Cellect Biotherapeutics Ltd: Consultancy. McGuirk:Novartis Pharmaceuticals Corporation: Honoraria, Other: speaker, Research Funding; Fresenius Biotech: Research Funding; Kite Pharma: Honoraria, Other: travel accommodations, expenses, speaker ; Gamida Cell: Research Funding; Astellas Pharma: Research Funding; Pluristem Ltd: Research Funding; Bellicum Pharmaceuticals: Research Funding. Rosen:Pluristem: Employment.

Autologous (auto) versus matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic (allo) hematopoietic cell transplantation (HCT) in follicular lymphoma (FL) patients (pts) with early chemoimmunotherapy failure (ECF): A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis.

7508 Background: Contrary to most FL, high-risk FL pts with ECF (i.e. relapse within 2 yrs of frontline chemoimmunotherapy) have a 5 yr OS of only 50%. (Casulo, JCO 2015). We used the CIBMTR database to compare autoHCT versus either MSD or MUD alloHCT as the first transplant approach in FL pts with ECF. Methods: Adult FL pts (age ≥18) undergoing autoHCT or alloHCT between 2002-2014 and receiving first line rituximab-based chemoimmunotherapies with evidence of ECF (defined as disease relapse or progression within 2 yrs of treatment initiation) were included. The primary endpoint was OS; secondary endpoints were progression-free survival (PFS), relapse and non-relapse mortality (NRM). Results: 440 pts had ECF (auto = 240, MSD = 105, MUD = 95) (Table 1). The 5 yr adjusted probabilities (AjP) of NRM were significantly lower with autoHCT (5%), versus MSD (17%) or MUD (33%) HCT (p&lt;0.0001). 5 yr AjP of relapse were significantly lower with MSD (31%) or MUD HCT (23%), versus autoHCT (58%; p&lt;0.0001). AjP of 5 yr PFS following auto, MSD and MUD HCT were 38%, 52% and 43% (p=.006) respectively. The AjP of 5 yr OS was significantly higher following autoHCT (70%) or MSD HCT (73%) versus MUD HCT (49%; p=0.004). Conclusions: AutoHCT for FL pts with ECF has low NRM and 5 yr OS rates (70%) that are provocatively higher than historical data (~50%). MSD HCT had the lowest relapse rate with similar survival. A prospective trial confirming the role of HCT in ECF FL is warranted. [Table: see text]

Adaptive NK Cell Expansion Is Associated with Reduced Relapse of Lymphoid Malignancies after Autologous Hematopoietic Cell Transplant

Introduction: Our group previously reported that latent or reactivated cytomegalovirus (CMV) after hematopoietic cell transplantation (HCT) leads to expansion of a CD56dimCD57+NKG2C+ "adaptive" natural killer (NK) cell subset that displays characteristics of immune memory. Here we report on the impact of these adaptive NK cells on outcomes after autologous (auto) HCT in patients with lymphoid malignancies.Methods: Based on our prior studies in allogeneic transplant, we hypothesized that patients with high absolute numbers of CD56dimCD57+NKG2C+ "adaptive" NK cells at day 28 post auto HCT ("high group") would have lower risk of relapse compared to those with low numbers ("low group"). Secondary outcomes included overall survival (OS) at 2 years and incidence of bacterial, fungal and viral infections 3 months post HCT. Patients with CMV reactivation were excluded because of low incidence (5%). Recursive partitioning was used to differentiate a high (≥1.529 adaptive NK cells/µL, n=88) from low (<1.529 cells/µL, n=25) group based on the largest Gray test statistic at day 28, which predicted the risk of relapse. Kaplan-Meier curves were used to estimate the probability of relapse and disease free survival (DFS) through 2-year post-HCT, and the log-rank test was used for comparisons. Fine-Gray and Cox regression was used to examine the independent effect of factors on relapse and DFS, respectively.Results: Overall, mean age at HCT was 55.8 years, 52% were males and 64% were CMV seropositive. Diagnoses included Hodgkin (13%) and non-Hodgkin lymphoma (36%) and multiple myeloma (51%) [Table 1]. Almost all patients (96%) in the low group vs. 77% in the high group had Karnofsky performance scores (KPS) of 90 or higher at the time of HCT, p=0.04.There were no other differences between the baseline characteristics of the groups. Cumulative incidence of relapse at 2-years was 34% (95% confidence interval [CI] 23-44%) in the high group compared with 70% (95% CI 49-91%) in the low group (p=0.0012). 2-year DFS rates were 63% (95% CI 51-72%) and 30% (95% CI 12-50%), respectively (p=0.0032) [Figure 1]. Overall survival (OS) at 2-years was 87% (95% CI 77-92%) in the high group vs. 84% (95% CI 63-94%) in the low group, p=0.70. Cumulative incidence of bacterial infections (25% vs. 24%, p=0.91), viral infections (2% vs. 0%, p=0.9) or fungal infections at 90 days (4% each, p=0.9) were similar in high and low groups. After adjusting for CMV serostatus, diagnosis, disease status, age, gender, KPS and comorbidity index in multivariate analysis, the high group had significantly lower risk of relapse (hazard ratio [HR] 0.22, 95% CI 0.11-0.46, p<0.0001) and improved DFS (HR 0.28, 95% CI 0.13-0.56, p<0.001) compared with the low group. The protective effect of CD56dimCD57+NKG2C+ NK cells on relapse (HR 0.12, 95% CI 0.05-0.30, p<0.0001) and DFS (HR 0.14, 95% CI 0.06-0.33, p<0.0001) was noted only in CMV seropositive patients, but not in seronegative individuals.Conclusion: We show that patients with lymphoid malignancies with high absolute counts of "adaptive" CD56dimCD57+NKG2C+ NK cells at day 28 post auto HCT had significantly superior DFS and lower risk of relapse compared with patients with low absolute "adaptive" NK cell counts. There was no difference in the risk of bacterial, fungal or viral infections or in OS between the groups. These provocative data suggest that interventions to increase numbers of these adaptive NK cells might provide a novel means of enhancing protection against relapse following auto HCT. [Display omitted] [Display omitted] DisclosuresCichocki:Fate Therapeutics, Inc: Research Funding. Miller:Oxis Biotech Scientific Advisory Board: Membership on an entity's Board of Directors or advisory committees.

Patient-Reported Quality of Life Is an Independent Predictor of Survival after Allogeneic Hematopoietic Cell Transplantation: A Secondary Analysis from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902

INTRODUCTIONPatient reported outcomes (PROs) including symptoms and health related quality of life (HRQOL) predict mortality in multiple cancers, such as myeloma, head and neck, lung and prostate cancer. The relationship of PROs with survival is not clear in hematopoietic cell transplantation (HCT). We tested three hypotheses about the relationship between HRQOL and survival after HCT: (1) Pre-HCT HRQOL (particularly physical HRQOL) reflects functional status and predicts survival after allogeneic (allo) HCT independently of traditional risk factors and indices; (2) Post-HCT change in physical HRQOL reflects the “toll” of the HCT and predicts subsequent outcomes, including survival, among early survivors; (3) Since autologous (auto) HCT is associated with lower risks for treatment-related morbidity and mortality, PROs may not be as predictive for this group. METHODSWe tested these hypotheses using data from the 711 participants in BMT CTN 0902 (sponsored by NHLBI and NCI, NCT 01278927), a randomized study of pre-transplant exercise and stress management training for patients undergoing auto or allo HCT. Because the primary analysis for BMT CTN 0902 did not show a significant effect for exercise or stress management training, intervention groups were combined for these analyses. However, auto and allo recipients were analyzed separately because of the expected substantial differences in the subsequent risks for morbidity and mortality in the two populations. The HRQOL measures used were the physical component score (PCS) and mental component score (MCS) from the SF-36, measured pre-HCT and at day 100. RESULTSAmong 310 alloHCT recipients with a median follow-up of 23 months, while there were no pre-HCT clinical covariates (including age, conditioning intensity, donor type, graft source, disease, disease stage) that predicted survival, pre-HCT physical HRQOL (PCS on the SF-36) was strongly prognostic for survival (HR for death of 0.72 per 10 points increase, 95% CI 0.60-0.85, p<0.001) while pre-HCT MCS was not (HR 0.99, 95% CI 0.84-1.16, p=0.29). Survival estimates for the first, second, third, and fourth quartiles of baseline PCS were, respectively, 67%, 72%, 81%, and 91% at 6 months and 50%, 65%, 75%, and 83% at one year (Figure 1). Among the eight SF-36 subscales, higher pre-HCT Physical Functioning and General Health scores were strongly associated with better survival. Among day 100 survivors, the PCS change score from baseline to Day 100 was also strongly prognostic for subsequent survival after adjusting for pre-HCT PCS (HR 0.55 per 10 points improvement, 95% CI 0.42-0.72, p<0.001) as was the MCS change score after adjusting for pre-HCT MCS (HR 0.70, 95% CI 0.56-0.89, p=0.003). In models that included patient age and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), the EBMT Score, or the Disease Risk Index (DRI), the findings for both pre-HCT values and change scores remained statistically significant with similar hazard ratios, suggesting that PROs convey independent prognostic information for survival despite inclusion of traditional risk factors. Analyses of transplant-related mortality (TRM) in alloHCT recipients showed similar patterns. Higher pre-HCT PCS was predictive of lower TRM. Among patients alive and disease-free at day 100, PCS change score was also associated with lower TRM after adjusting for pre-HCT PCS (HR 0.28, 95% CI 0.17-0.47, p<0.001) and the HCT-CI, EBMT and DRI; pre-HCT MCS and change in MCS did not predict TRM. Among autoHCT recipients (n=337), there were no pre-HCT clinical covariates that predicted survival. Pre-HCT HRQOL also was not prognostic of survival in autoHCT (physical PCS from the SF-36 p=0.82, mental MCS from the SF-36, p=0.56), nor were early changes in either the PCS or the MCS. CONCLUSIONIn summary, among alloHCT recipients who participated in BMT CTN 0902, lower pre-HCT physical HRQOL and early decline in physical HRQOL were strongly predictive for worse overall survival and higher transplant-related mortality. These results suggest that patient-reported data are an important component of risk assessment and could assist in clinical decision-making. High-risk individuals could be targeted for different management strategies or more aggressive supportive care interventions to reduce treatment-related morbidity and mortality in this population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clostridium Difficile Infection in Patients Undergoing Hematopoietic Cell Transplantation. Results from the Transplantation Group at the Catholic University Hospital in Santiago, Chile

▪Introduction: Patients undergoing hematopoietic cell transplantation (HCT) have an increased risk of Clostridium difficile infection (CD) and multiple risk factors have been found. Literature reports CD infection in nearly 20% of transplanted patients. No information about this infection in HCT patients has been reported in Chile.Patients and Methods: We performed a retrospective analysis of 250 patients undergoing HCT at the Catholic University Hospital in Santiago, Chile, between 2000 and the first semester of 2013, including allogeneic (allo) HCT and autologous (auto) HCT patients. Statistical analysis of the data was conducted using SPSS Statistics v21.Results: Of the 250 transplanted patients studied, 59% (n=147) were allo-HCT and 41% (n=103) were auto-HCT. The mean age was 39 years old (range: 15-69), with a male predominance (151 patients; 60%). The main indication for HCT was acute leukemia (n=104; 42%) followed by multiple myeloma (n=36; 14%) and lymphoma (n=49; 20%). 93% of patients received myeloablative (MA) conditioning regimen, and all of them received proton pump inhibitors and prophylactic antibiotics during the previous months of the HCT. Of the 250 patients studied, 192 (77%) had at least one episode of diarrhea that required study, among them 13% (n=25) were documented as positive for CD (toxin assay or PCR test), the mean age of this group was 36 years old (range: 18-62), also with a male predominance (15 patients; 60%). All of the infected patients had mild to moderate diseases and there were no deaths attributed to it. 80% (n=20) of the infected patients underwent allo-HCT and 20% (n=5) auto-HCT. In the allo-HCT group, 53% had acute lymphoblastic leukemia (ALL), 6% acute myeloid leukemia (AML), 24% chronic myeloid leukemia (CML) and 12% other causes. In the auto-HCT group, 40% were transplanted due to multiple myeloma, 20% amyloidosis, 20% germinal cancer and 20% acute myeloid leukemia. No patient required total central parenteral nutrition previous to the infection. During the 3 months before HCT, 84% (n=21) of the infected patients used antibiotics including cephalosporins, carbapenem, aminoglicosides and vamcomycin. The overall incidence of CD infection in the first week, month and year after transplant, was 4.0%, 6.4% and 10%, respectively, with a median time frame from transplantation to infection diagnosis of 20 days. In auto-HCT, 7 days, 30 days and 1 year CD incidence was 1.9, 2.9 and 4.9%, respectively. In allo-HCT, 7 days, 30 days and 1 year CD incidence was 5.4, 8.8 and 13.6%, respectively. There was no significant statistical difference in overall survival (OS) between the infected and non-infected patients one year after the transplant (OS 67.6% for CD negative vs. 72.0% for CD positive, p=0.61).Conclusions: In our institution CD infection in patients undergoing HCT had a similar incidence to other reports. Most of cases occur before the first week after HCT (40% of the cases), and the incidence of the infection remained stable during the first year after the procedure. We identified the type of transplant (allo-HCT 3 times higher risk than auto-HCT) and disease (ALL 3 times higher risk than AML) as risk factors for CD infection. DisclosuresNo relevant conflicts of interest to declare.

Comorbidity, History of Alcohol Disorders, and LDH Predict Non-Relapse Mortality (NRM) Among Recipients of Autologous Hematopoietic Cell Transplantation (HCT) for Lymphoma

s / Biol Blood Marrow Transplant 20 (2014) S57eS71 S67 cigarette smoking, and other demographics do not. Our simple risk model could aid in decision-making in the clinic and highlights areas of potential intervention to reduce NRM following auto HCT.

Risk Factors for Musculoskeletal Symptoms in 5-20 Year Survivors Who Received Myeloablative Hematopoietic Cell Transplant (HCT)

s / Biol Blood Marrow Transplant 20 (2014) S57eS71 S67 cigarette smoking, and other demographics do not. Our simple risk model could aid in decision-making in the clinic and highlights areas of potential intervention to reduce NRM following auto HCT.

Autologous and Allogeneic Donor Transplantation for Mantle Cell Lymphoma in Rituximab Era: Impact of Pre-Transplant Burden On Survival.

AbstractAbstract 3092▪▪This icon denotes a clinically relevant abstractThe survival for patients with mantle cell lymphoma (MCL) can be prolonged by the use of rituximab-containing intensive chemotherapies and hematopoietic cell transplantation (HCT). However, the optimal application of autologous and allogeneic HCT in the rituximab era remains uncertain.We report 66 patients with MCL who underwent HCT (38 autologous and 28 allogeneic) at the University of Minnesota between 1999–2010. Eighty eight percent received a Rituximab-containing induction chemotherapy. Autologous HCT patients were older (66% were ≥60 years of age), 70% were in CR1 and all except 1 were chemosensitive. Two patients had minimal residual disease in the marrow (MRD) and two-thirds were PET negative at the time of transplant. Allogeneic HCT patients were younger (85% were <60 years old), 19% were in CR1 and 21% had chemo-resistant disease. At the time of transplant, 80% of allogeneic patients were PET positive and 18% of patients had detectable marrow MCL. Allogeneic recipients had a significantly longer time from diagnosis to transplant (allo 17.7 months vs auto 7.6 months; p≤0.01).At a median follow-up of 3.5 years (range 1.1–9.2 years), the 5-year disease free survival (DFS) and overall survival (OS) of the autologous cohort were 59% and 62%, respectively (Table). In univariate analyses for DFS, younger age, absence of splenic and extranodal disease at diagnosis and shorter time to transplant were significantly associated with better survival (age <60 vs. ≥60 yrs 92% [95 CI 57–99%] vs. 43%[95 CI 18–66%]; p=0.04; extra nodal disease positive 25% [95 CI 2–63%] vs negative 77% [95 CI 48–91%]); p=.02; diagnosis to HCT time <8 months vs. ≥8 months 79% [95 CI 51–92%] vs 32% [95 CI 7–62%]; p=0.03). Patients with residual disease pre auto HCT (PET scan + and/or MRD) had significantly worse DFS (residual disease positive: 46% (95 CI 14–73%) vs negative 68% (95 CI 33–87%); p=0.04). The type of induction chemotherapy, disease status (CR1 vs other), blastoid variant or comorbidity index did not impact DFS or OS. The cumulative incidence of relapse and treatment related mortality (TRM) are shown. Notably, none of the patients with negative pre auto- transplant PET scan and lack of MRD relapsed at 2 years (p=<.01). In multivariate analysis, residual lymphoma (by PET or MRD pos) was the single significant factor associated with 5-fold lower rate of DFS compared to no residual disease (HR: 5.26 (96% CI 1.17–23.55); p=0.03).Twenty-eight patients received allogeneic transplants (17 sibling donor, 10 umbilical cord blood, 1 unrelated donor). Half were transplanted using a reduced intensity conditioning (RIC) regimen and five patients failed a prior autograft. At a median follow-up of 6.7 years (range 1–10.3 years), the 5-year DFS and OS were 34% and 52%, respectively (Table). In univariate analysis the 5 year DFS was not significantly affected by chemosensitivity, disease status, PET positivity or MRD prior to transplant (Chemo sensitive: 41% (95 CI 20–61%) vs. resistant 17% (95 CI 1–52%) p=.38; CR1/PR1 40% (95 CI 5–75%), resistant 17% (95 CI 1–52%%), relapse 42% (95 CI 18–65) p=.66; PET pos 33% (95 CI 10–59%) vs PET neg 67% (95 CI 5–95%) p=.63). DFS following myeloablative (MA) conditioning was similar to that of RIC (43% [95 CI 16–68%] vs. 27% [95 CI 8–50%]; p=.57); MRD not shown). OS was not significantly affected by PET or marrow status prior to HCT. The cumulative incidence of 2 year relapse and 1 year TRM are shown. No relapses occurred in the MA cohort compared to a 29% relapse rate (95 CI 6–53%) after RIC HCT (p=.08). Conversely, 2 year TRM for allograft recipients was 2 times higher with MA conditioning (33% (95 CI 7–59%) compared to RIC (15% (95 CI 0–32%); p=.29).Survival of MCL patients post autologous and allogeneic HCT has improved in the last decade. Long-term disease control is observed following autologous HCT in CR1 or for relapsed MCL, particularly if a PET negative state can be attained pre-transplant. Patients with more advanced disease and higher MCL burden prior to HCT can benefit from allogeneic transplantation. Novel therapies designed to better control MCL pre-transplant and to reduce post-transplant relapse after RIC HCT may further improve survival.Transplant Type5 yr DFS (95% CI)5yr OS (95% CI)2 yr Relapse (95% CI)1 yr TRM (95% CI)Autologous59% (37-76%)62% (39-79%)14% (3-24%)5% (0-12%)Allogeneic34% (17-51%)52% (32-69%)25% (8-43%)19% (4-34%) Disclosures:No relevant conflicts of interest to declare.

What Is the Role of Transplantation for Indolent Lymphoma?

Despite advances in chemoimmunotherapy, indolent B-cell non-Hodgkin lymphomas (B-NHLs) are generally not considered curable with this approach. Much attention has been paid to the prospect of hematopoietic cell transplantation (HCT) as a way to improve long-term outcomes for this group of diseases. Autologous (auto) HCT provides intensive conditioning therapy followed by rescue of hematopoiesis, and this has been shown in randomized studies to prolong survival compared with more standard chemotherapy, albeit with increased short-term toxicity and the potential for higher rates of secondary malignancies. Allogeneic (allo) HCT can provide anticancer effects beyond the conditioning therapy through the immune-mediated graft-versus-lymphoma (GVL) effect. It can be administered following myeloablative (MA) conditioning or reduced-intensity (RI) regimens aimed at sufficiently suppressing the patient's immune system to allow engraftment of donor hematopoiesis. However, this same potentially curative alloreactivity of the engrafted immune system can lead to graft-versus-host disease (GVHD), a significant cause of morbidity and mortality following allo HCT. This article will discuss the current role of both auto HCT and allo HCT in the management of indolent lymphoma as well as the relative risks and benefits of each approach such that the reader can place this in context of the multitude of options available for patients with indolent B-NHL.