Search

PDF file - 58K, Study design and patient flow by intent to treat (ITT).

PDF file - 53K, Validation of gene expression data using QPCR compared to microarray values (data reported as fold change).

Purpose: This phase II study evaluated bortezomib-based secondary induction and stem cell mobilization in 38 transplant-eligible patients with myeloma who had an incomplete and stalled response to, or had relapsed after, previous immunomodulatory drug-based induction.Experimental Design: Patients received up to six 21-day cycles of bortezomib plus dexamethasone, with added liposomal doxorubicin for patients not achieving partial response or better by cycle 2 or very good partial response or better (≥VGPR) by cycle 4 (DoVeD), followed by bortezomib, high-dose cyclophosphamide, and filgrastim mobilization. Gene expression/signaling pathway analyses were conducted in purified CD34+ cells after bortezomib-based mobilization and compared against patients who received only filgrastim ± cyclophosphamide. Plasma samples were similarly analyzed for quantification of associated protein markers.Results: The response rate to DoVeD relative to the pre-DoVeD baseline was 61%, including 39% ≥VGPR. Deeper responses were achieved in 10 of 27 patients who received bortezomib-based mobilization; postmobilization response rate was 96%, including 48% ≥VGPR, relative to the pre-DoVeD baseline. Median CD34+ cell yield was 23.2 × 106 cells/kg (median of 1 apheresis session). After a median follow-up of 46.6 months, median progression-free survival was 47.1 months from DoVeD initiation; 5-year overall survival rate was 76.4%. Grade ≥3 adverse events included thrombocytopenia (13%), hand–foot syndrome (11%), peripheral neuropathy (8%), and neutropenia (5%). Bortezomib-based mobilization was associated with modulated expression of genes involved in stem cell migration.Conclusion: Bortezomib-based secondary induction and mobilization could represent an alternative strategy for elimination of tumor burden in immunomodulatory drug-resistant patients that does not impact stem cell yield. Clin Cancer Res; 19(6); 1534–46. ©2013 AACR.

PDF file - 72K, Most common all-grade and grade ≥3 AEs during DoVeD induction and bortezomib-based stem cell mobilization.

PDF file - 60K, Kaplan-Meier estimates of (A)PFS and (B)OS in patients in the ITT population (N-38).

PDF file - 59K, Responses rates after DoVeD induction, bortezomib- or non-bortezomib-based mobilization, and SCT.

The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using in vivo T-cell depletion. Adenovirus viremia was found in 59 patients for a cumulative incidence of 10% by one hundred days and 23% (95% CI 20-26%) by one year. There was a higher incidence of viremia associated with cord blood transplant (p = .04). No other patient, donor or transplant characteristics were identified that predicted for viremia. In 47 patients (80%), viremia remained well below 200,000 copies/mL and resolved. Twelve patients developed high level viremia. Treatment with antivirals and in some cases adoptive cell therapy, was often ineffective and only two survived. Low lymphocyte count at initial detection of adenovirus viremia was the best predictor of uncontrolled disease.

We evaluate the safety of bendamustine as a bridge to stem cell transplantation (SCT) in patients with relapsed/refractory lymphoma and residual disease after salvage therapy. Thirty-four subjects without complete responses (CR) received bendamustine 200 mg/m

Epstein-Barr virus (EBV) reactivation and EBV-related post-transplantation lymphoproliferative disorder (PTLD) are often fatal complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk of EBV reactivation may be mitigated by depletion of B cells with rituximab. Starting in January 2020, allo-HSCT recipients undergoing T-cell depletion with alemtuzumab received 1 dose of rituximab before transplantation. The objective of this study was to evaluate the cumulative incidence of EBV reactivation and EBV-PTLD in recipients of allo-HSCT and in vivo T-cell depletion with alemtuzumab who received pre-HSCT rituximab compared to patients who did not. This was a single-center retrospective analysis of adult patients who consecutively received an HLA-identical allo-HSCT between January 2019 and May 2021 and in vivo T-cell depletion with alemtuzumab. Patients were included in the rituximab cohort if they received rituximab within 6 months before their transplantation. The primary endpoint was incidence of EBV reactivation at day 180 among those receiving pre-HSCT rituximab versus those not receiving rituximab. Secondary endpoints included cumulative incidence of EBV-PTLD at 1 year, time to engraftment, immune reconstitution, and incidence of infections and acute graft-versus-host disease (aGVHD) at day 180. Eighty-six consecutive patients who received an allo-HSCT with alemtuzumab T-cell depletion were reviewed; 43 patients who received pre-HSCT rituximab after our protocol modification were compared to 43 patients who did not receive pre-HSCT rituximab before this change. Median age was 57 (interquartile range [IQR] 40-69) years, and the majority of patients had acute myeloid leukemia or myelodysplastic syndrome. Baseline characteristics were similar between the cohorts. EBV reactivation at day 180 occurred in 23 (53%) patients without prior rituximab exposure versus 0 patients with pre-HSCT rituximab exposure (P.0001). Similarly, 6 patients without prior rituximab exposure developed PTLD at 1 year compared to no cases of PTLD among patients receiving pre-HSCT rituximab. There was no difference in neutrophil engraftment, incidence of infections, or aGVHD at day 180 between the 2 cohorts. There was a delay in time to platelet engraftment in the rituximab cohort (median 16 [IQR 15-20] days versus 15 [IQR 14-17] days; P = .04). Administration of pre-HSCT rituximab before allo-HSCT in patients receiving T-cell depletion with alemtuzumab was associated with a significant decrease in the risk for EBV reactivation and EBV-PTLD, without increasing aGVHD or infection rates.

Alternative donor transplantation with the haplo-cord platform allows the use of a lower-dose single umbilical cord blood unit (CBU) by co-infusion of third-party CD34+-selected cells from a haploidentical relative, which provides early transient engraftment while awaiting durable CBU engraftment. In our experience, ~15% of patients lack a suitable haploidentical donor. Here we report 26 patients who underwent haplo-cord transplant using CD34+-selected partially matched unrelated donor grafts. Twenty-four were conditioned with fludarabine/melphalan +/− low-dose TBI (n = 16). Twenty-five received ATG and all received posttransplant tacrolimus and mycophenolate mofetil. Median time to neutrophil and platelet recovery was 11 and 18 days. CBU engraftment, with CD33 and CD3 >5% cord chimerism in the myeloid/lymphoid compartment by day +60, occurred in 20 of 24 patients (83%). Incidence of grade 2–4 acute graft-versus-host disease (GVHD) was 27% at day +100, and chronic GVHD was 4% at 1 year. Overall survival at 1 year was 54%. For patients in need of an alternative transplant who lack a haploidentical donor, haplo-cord transplantation using CD34+-selected partially matched unrelated donor grafts results in rapid engraftment with no increased rate of cord graft failure or GVHD.

Reduced-intensity conditioning (RIC) regimens, improved HLA matching, and better supportive care allow allogeneic stem cell transplant (alloSCT) to be offered to older patients. Only a small percentage of eligible patients between ages 65 and 74 years actually undergo alloSCT, and comprehensive outcome data from the aging population are still lacking. We examined the outcome of older patients who underwent alloSCT using melphalan-based RIC for hematologic malignancies at our institution. We identified 125 patients older than 65 years (median, 69; range, 66 to 77) who underwent matched related donor, matched unrelated donor, or combined haploidentical/umbilical cord alloSCT between 2012 through November, 2017. Among them, 52 (41.6%) and 70 (56%) had, respectively, intermediate and high/very high Center for International Blood and Marrow Transplant Research (CIBMTR) disease risk index (DRI). One hundred six patients (85%) received fludarabine/melphalan-based RIC regimen with either antithymocyte globulin (ATG) or alemtuzumab. The median time to neutrophil engraftment was 13 days (range, 8 to 37) and platelet engraftment 17 days (range, 9 to 169). The cumulative incidence of nonrelapse mortality was 11.5% at 100 days and 30.1% and 34.8% at 1 and 2 years, respectively. The cumulative incidence of relapse was 35% and 40% at 1 and 2 years. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) at day 100 and 6 months was 29.5% and 34.5%, and chronic GVHD at 6, 12, and 24 months was 2.5%, 5.2%, and 6.3%, respectively. With a median follow-up of 32 months, the 1-, 2-, and 3-year progression-free survival (PFS) was 34.6%, 24.4%, and 16.5%, respectively. The graft GVHD-free survival was 24.6%, 16.1%, and 9.3%, respectively. The 1-, 2-, and 3-year overall survival (OS) was 44.5%, 30.7%, and 26.5%, respectively. In multivariable analysis, low albumin was predictive of poor PFS and OS and high hematopoietic cell transplantation–specific comorbidity index, and CIBMTR DRI was predictive of worse graft GVHD-free survival. Among long-term survivors the median Karnofsky performance status was 80. Older patients, even when referred with advanced disease, can benefit from melphalan-based alloSCT with HLA-matched or alternative donor sources without discernible impact of donor source on outcome. Using alemtuzumab- or ATG-based in vivo T cell depletion, the incidence of chronic GVHD is extremely low. Performance status in survivors is excellent. Better predictors for outcome in this patient population need to be identified.

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT 01050946.

High-dose melphalan (MEL200) followed by autologous stem cell transplantation (ASCT) remains a standard of care for multiple myeloma (MM). Bendamustine induces responses in MM resistant to other alkylators. Our prior Phase I trial adding bendamustine to MEL200 transplant conditioning resulted in no additional toxicity. We now report a single-arm, phase II study that evaluated the efficacy of bendamustine 225 mg/m2 with MEL200 conditioning for ASCT in 18 patients with newly diagnosed MM (NDMM) and 17 with relapsed or refractory MM (RRMM). The primary end point was the complete response (CR/sCR) rate at day+ 100. Sample size was determined according to Simon's two-stage design. At stage 1, sixteen patients entered the study. As there were eight patients with CR/sCR, enrollment increased to 28 patients. Sixteen out of the first 28 evaluable patients achieved CR/sCR, meeting the design criteria. Enrollment was then expanded to a total of 35 patients. 51% achieved a CR/sCR. After a median follow-up of 65 months, 21 patients progressed, including 7 deaths. The median PFS for NDMM and RRMM was 48 and 45 months, respectively. Bendamustine/MEL200 conditioning resulted in excellent overall and depth of response as well as PFS, particularly in the RRMM patients, and is worthy of further investigation (NCT00916058).

Adoptive immunotherapy has shown efficacy in patients with relapsed/refractory acute myelogenous leukemia (AML). We conducted a prospective evaluation of cord blood (CB)-based adoptive cell therapy following salvage chemotherapy in patients with AML or myelodysplastic syndrome (MDS) and describe the safety and early outcomes of this approach. To enhance the antileukemic effect, we selected CB units (CBUs) with a shared inherited paternal antigen (IPA) and/or noninherited maternal antigen (NIMA) match with the recipients. Furthermore, the CBUs had total nucleated cell (TNC) dose

Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD) are common and potentially fatal complications after allogeneic transplantation with mismatched donors and T-cell depletion. Haplo-cord transplantation combines a mismatched UCB graft with third-party cells. Conditioning involves thymoglobulin. EBV reactivation and PTLD were common in initial patients. As of March 2017, we administered a prophylactic dose of rituximab 375 mg/m

Infectious diarrhea following hematopoietic cell transplantation (HCT) significantly contributes to morbidity and mortality. Most HCT recipients experience diarrhea in the post-transplantation period, and infectious pathogens are frequently detected during diarrheal episodes. However, little is known about how frequently these patients are colonized with gastrointestinal (GI) pathogens before their transplantation and whether colonization predicts future diarrheal illness. We sought to determine how frequently HCT recipients are colonized with GI pathogens before HCT and the degree to which pre-HCT colonization predicts post-transplantation infectious diarrheal illness. We conducted a prospective cohort study of allogeneic and autologous HCT recipients at a single center between December 2016 and January 2019. Stool samples were collected during the week before HCT, and formed samples were evaluated for the presence of 22 diarrheal pathogens using the BioFire FilmArray GI panel. We determined the frequency with which participants were colonized with each pathogen and identified factors associated with colonization. We then determined how frequently pretransplantation colonization led to post-transplantation diarrheal infections due to the colonizing pathogen and whether colonization was associated with increased number of days of post-transplantation diarrhea during the transplant hospitalization. We enrolled 112 asymptomatic patients (allogeneic, 61%; autologous, 39%) who had a formed stool specimen before HCT, of whom 41 (37%) had a GI pathogen detected. The most commonly detected organisms were Clostridioides difficile (n = 21; 19%), Yersinia enterocolitica (n = 9; 8%), enteropathogenic Escherichia coli (EPEC) (n = 6; 6%), and norovirus (n = 5; 4%). Female sex and previous C. difficile infection were associated with C. difficile colonization, and having non-Hodgkin lymphoma was associated with being colonized with a diarrheal pathogen other than C. difficile. Thirteen of 21 patients (62%) with pretransplantation C. difficile colonization developed a clinical C. difficile infection post-transplantation, and 8 of 10 patients (80%) colonized with EPEC or enteroaggregative E. coli developed post-transplantation infections due to their colonizing pathogen. Pretransplantation C. difficile colonization was also associated with an increased duration of post-transplantation diarrhea (P = .048). Conversely, none of the 9 patients with pretransplantation Yersinia enterocolitica colonization developed a post-transplantation Y. enterocolitica infection. Patients admitted for HCT are frequently colonized with a diverse range of GI pathogens. Colonization with C. difficile colonization and diarrheagenic E. coli is frequently associated with post-transplantation diarrheal infections caused by these organisms, but the clinical significance of colonization with other GI pathogens is not clear.

We conducted a prospective evaluation of cord blood (CB)–derived adoptive cell therapy, after salvage chemotherapy, for patients with advanced myeloid malignancies and poor prognosis. Previously, we reported safety, feasibility, and preliminary efficacy of this approach. We present updated results in 31 patients who received intensive chemotherapy followed by CB infusion and identify predictors of response. To enhance the antileukemic effect, we selected CB units (CBU) with shared inherited paternal antigens and/or noninherited maternal antigens with the recipients. Twenty-eight patients with acute myeloid leukemia (AML), 2 with myelodysplastic syndrome, and 1 in chronic myeloid leukemia myeloid blast crisis were enrolled; 9 had relapsed after allogeneic transplant. Response was defined as

PGF implies persistent cytopenia in the presence of predominant donor chimerism. We examined contributors to PGF in 104 HCT recipients who survived ≥100 days without relapse or major complications. Surrogate parameters for PGF were: Hg10 g/dl, RBC transfusion dependence, platelet count20 × 10

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for a variety of malignant and nonmalignant hematologic disorders, but its efficacy is limited by transplant-rel...

New York City has been at the epicenter of the coronavirus disease 2019 (COVID‐19) pandemic that has already infected over a million people and resulted in more than 70,000 deaths as of early May 2020 in the United States alone. This rapid and enormous influx of patients into the health care system has had profound effects on all aspects of health care, including the care of patients with cancer. In this report, the authors highlight the transformation they underwent within the Division of Hematology and Medical Oncology as they prepared for the COVID‐19 crisis in New York City. Under stressful and uncertain conditions, some of the many changes they enacted within their division included developing a regular line of communication among division leaders to ensure the development and implementation of a restructuring strategy, completely reconfiguring the inpatient and outpatient units, rapidly developing the ability to perform telemedicine video visits, and creating new COVID–rule‐out and COVID‐positive clinics for their patients. These changes allowed them to manage the storm while minimizing the disruption of important continuity of care to their patients with cancer. The authors hope that their experiences will be helpful to other oncology practices about to experience their own individual COVID‐19 crises.

Alternative donor transplantation with the haplo-cord platform allows the use of a lower-dose single umbilical cord blood unit (CBU) by co-infusion of third-party CD34

Haplo/cord transplantation combines an umbilical cord blood (UCB) graft with CD34-selected haploidentical cells and results in rapid hematopoietic recovery followed by durable UCB engraftment. We compared outcomes of transplants in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who received either HLA-matched unrelated donor (MUD) cells or haplo/cord grafts. Between 2007 and 2013, 109 adults ages 50 and older underwent similar reduced-intensity conditioning with fludarabine and melphalan and antibody-mediated T cell depletion for AML (n = 83) or high-risk MDS (n = 26) followed by either a MUD (n = 68) or haplo/cord (n = 41) graft. Patient characteristics were similar for each graft source except for more minority patients receiving a haplo/cord transplant (P = .01). One half of the AML patients were not in remission. Two-year progression-free survival (PFS), overall survival (OS), and graft-versus-host disease–free relapse-free survival were 38%, 48%, and 32.1% for MUD and 33%, 48%, and 33.8% for haplo/cord transplants (P = .62 for PFS; P = .97 for OS; P = .84), respectively. Acute grades II to IV and chronic graft-versus-host-disease rates did not differ at 19.5% and 4.9% in haplo/cord compared with 25% and 7.4% after MUD (P = .53 and P = .62, respectively). Multivariate analysis confirmed no significant differences in transplant outcomes by donor type. Haplo/cord reduced-intensity transplantation achieves similar outcomes relative to MUD in older AML and MDS patients, making this a promising option for those without matched donors.

Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, there is limited and conflicting data regarding the optimal timing of G-CSFs post-transplant. A retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center (NYP/WC) from November 5, 2013 to August 9, 2016 of adult inpatient autologous PBSCT patients who received G-CSF empirically starting on day +5 (early) versus day +12 only if absolute neutrophil count (ANC) was

Introduction: Acute myeloid leukemia (AML) is heterogenous disease with a range of cytogenetic and molecular changes. Several molecular mutations identified in AML patients at diagnosis have prognostic implications and play important roles in guiding induction and consolidative treatment decisions. The prognostic impact of mutations peri allogeneic stem cell transplant are less well characterized. In this study, we examine the significance of pre and by D100 Post-transplant mutation status in AML patients underwent Fludarabine/Melphalan conditioned reduced intensity allogeneic stem cell transplant (SCT). Methods: AML patients who are in morphologic complete remission (CR1 or greater) with available molecular mutation at diagnosis, within 6 weeks prior to allogeneic SCT, and by 100 days post-transplant were included. Variables analyzed included baseline demographics, clinical variables (CIBMTR disease risk index (DRI), type of transplant, ELN risk, performance status) and 23 recurring molecular mutations. Analysis was also performed by grouping mutations into six pre-defined gene groups based on gene function (Table 2). Multivariable cox regression analysis was adjusted for age, gender, DRI and molecular mutation. Backward selection method was used to select the best combination of genes that is associated with overall survival (OS) and relapse-free survival (RFS). Results : A total of 142 AML patients with molecular genetic data available from 2014 to June, 2020 at Weill Cornell Medicine/New York Presbyterian Hospital were analyzed. Clinical characteristics of the patients are summarized in Table 1. The median age was 58 years (range 20 -78). Total of 261 mutations were detectable at diagnosis (Table 3). Prior to allo SCT and by D100, the detectable mutations were 87 and 40 respectively, which represent 56 and 26 patients. High-dose chemotherapy was less effective on clearing DNMT3A, ASXL1, TET2 (DAT) or IDH mutations, resulting in over-representation of DAT and IDH mutations prior to transplant. With a median follow-up time of 25 months, the median overall survival for the group was 40.8 months. The presence of mutations in TP53 at diagnosis was associated with worse OS by both univariate (HR 3.67, p=0.0030, CI 1.56-8.68) and multivariate analysis (HR 4.75, p=0.0014, CI 1.82-12.39) with median OS reduced from 49.3 to 19.3 months (p=0.002). High CIBMTR DRI (HR 0.17, p=0.0018, CI 0.05-0.51) predicted reduced OS and RFS, and Age >60 at diagnosis was associated with worse OS (HR 1.7 CI 1.04-3, p 0.03). Presence of any molecular mutation prior to transplant did not impact OS or RFS. For patients with any persistent mutations by D100 post-transplant, both OS ( HR 2.04, p 0.027, CI 1.08-3.8) and RFS (HR 1.99, p 0.025, CI 1.09-3.6,) were reduced in the univariate analysis, but not on multivariate analysis (HR 1.88, p 0.5, CI 0.99-3.49). Analysis based on six mutational groups (table 2) did not show any difference in their OS or RFS. However, worse RFS was independently associated with persistent IDH1 (HR 3.8, p 0.004, CI 1.07-56,), TET2 (HR 3.9, P 0.04, CI 1.04-14.1), and FLT3-ITD (HR 4.5, p 0.01, CI 1.7-52). Worse OS was independently associated with persistent TET2 (HR 3.9, p 0.013, CI 1.04-14.1), with a trend towards worse OS for IDH1, FLT3-ITD, with a trend towards worsening OS and RFS for ASXL1 (OS HR 7.4, p 0.06, CI 0.86 -63; RFS HR 4.9, p 0.06, CI 0.9-26) and DNMT3A (OS HR 2.3, p 0.12, CI 0.86-6.9; RFS 2.9, p 0.08, CI 0.98-8). Association with worse clinical outcomes remained significant after multivariate analysis for TET2 (both OS HR 3.98 p 0.041, CI1.07- 32 and RFS HR 5.8, p 0.032, CI 1.1- 29), IDH1 (RFS HR 8.02, p 0.049, CI 1.02 - 65) and FLT3-ITD (RFS HR 11.4, p0.010, CI 2.2- 80). Conclusions: Presence of TP53 mutations was associated with worse OS. Presence of pre-transplant mutation did not impact RFS or OS. Persistent presence of mutations in TET2, IDH1 and FLT3-ITD after Fludarabine/melphalan conditioning regimen allogeneic SCT were associated with shorter RFS and OS (in the case of TET2) independent of CIBMTR DRI. This analysis supports association of adverse outcomes in AML patients with selected persistent mutations by D100 post-transplant in reduced intensity transplant setting. Post-transplant strategies that can further eliminate persistent mutations should be investigated in prospective studies. Figure 1 Figure 1. Disclosures Lee: Pin Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Innate: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Desai: Kura Oncology: Consultancy; Bristol Myers Squibb: Consultancy; Agios: Consultancy; Takeda: Consultancy; Janssen R&D: Research Funding; Astex: Research Funding. Ritchie: Protaganist: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Speakers Bureau; Celgene/BMS: Consultancy, Other: travel support, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding; ARIAD Pharmaceuticals: Ended employment in the past 24 months, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Astellas: Consultancy, Research Funding; NS Pharma: Research Funding; Abbvie: Consultancy, Honoraria; Jazz: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Roboz: MEI Pharma - IDMC Chair: Consultancy; Daiichi Sankyo: Consultancy; Helsinn: Consultancy; Jazz: Consultancy; Bristol Myers Squibb: Consultancy; Glaxo SmithKline: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; Mesoblast: Consultancy; Blueprint Medicines: Consultancy; Jasper Therapeutics: Consultancy; AbbVie: Consultancy; Actinium: Consultancy; Agios: Consultancy; Amgen: Consultancy; Astex: Consultancy; Astellas: Consultancy; AstraZeneca: Consultancy; Bayer: Consultancy; Janssen: Research Funding; Pfizer: Consultancy; Roche/Genentech: Consultancy.

Introduction: Pulmonary complications constitute a major cause of morbidity and mortality in the post-hematopoietic cell transplant (HCT) period. While Chest X-ray (CXR) is customarily used for screening, we have utilized chest computed tomography (CT) within one month of transplant. Here we aim to characterize the prevalence of abnormalities and their impact on the eligibility for allogenic (allo) HCT and outcomes post-transplant. Methodology: We conducted a single center retrospective study of all patients who were evaluated for allogenic HCT from January 2013 through December 2020 in New York Presbyterian Hospital - Weill Cornell Medicine (NYP-WCM). All patients who had chest CT as part of their pre-transplant evaluation were included for analysis. Results: We identified 478 patients who had Chest CT screening. In 396 CT chest was normal or confirmed previous abnormalities. Eighty-two patients (17%) had previously undetected abnormalities (Figure 1). The most frequent abnormalities were pulmonary nodules (defined as nodules of 4 mm or greater) in 27 patients (31%), ground-glass opacities (GGO) in 21 patients (25%), Pneumonia in 18 patients (21%). Miscellaneous findings not related to the primary disease were found in 12 patients (14%) including thyroid nodules, breast nodules and hemangioma of the liver. A new malignancy was found in 6 patients (7%) and incidental pulmonary embolism (PE) in 2 patients (2%) (Figure 2). There were 5 (6%) patients who were ultimately excluded from transplant due to CT chest findings (simultaneous CXR showed abnormalities in only 1 out of 5). Three of those patients were found to have invasive fungal infection, and the other two had unrecognized metastatic lung cancer. For 19 patients (23%), transplant was delayed for diagnostic procedure and/or treatment of pulmonary findings (CXR showed abnormalities in only 3 patients out of 19). The most common reason for delay was lung infection requiring treatment. Thirty-two patients (41%) out of 77 patients with abnormal CT scan who eventually underwent transplant, have died . Sixteen died after relapse, and 16 from non-relapse mortality (NRM) with pulmonary complications playing a role in 13 patients (Figure 3). Conclusion: 17% of patients who had a pre-transplant CT chest had abnormalities that warranted further evaluation. In 23% of these patients, these findings led to a delay in transplant for further optimization. Six percent were deemed ineligible for transplant due to absolute contraindications that were incidentally discovered on chest CT. Initial screening CXR failed to identify a significant number of abnormalities. Our data suggests that chest CT imaging should be part of the routine pre-transplant evaluation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Direct thaw and administration of previously cryopreserved peripheral blood stem cell products is a commonly used practice and should be performed rapidly to reduce cellular damage caused by dimethyl sulfoxide exposure. Cells are typically thawed at the bedside and infused by gravity through a high-flow-rate central venous catheter. An existing nontunneled catheter is occasionally used instead and often results in a slower infusion rate. To ensure expedient and consistent infusions, we validated and implemented the use of an infusion pump for thawed peripheral blood stem cells. Study design and methods Validation was performed in two phases: in vitro simulation and in vivo clinical assessment. Total nucleated cell recovery and viability plus progenitor cell viability and potency were compared in vitro between two cryopreserved peripheral blood stem cell units that were either passed through a preset infusion pump or drained by gravity. The infusion rate, adverse events, and engraftment times were retrospectively compared between patients who received infusions by infusion pump (n = 35) and by gravity (n = 38). Results No significant differences were observed in vitro between the infusion methods for all measured variables. Overall infusion rates were similar in vivo for both groups but were significantly lower for patients who had nontunneled catheters that delivered the infusion by gravity. The time to neutrophil and platelet engraftment was similar for both groups. Conclusion This is the first study to assess the use of an infusion pump for stem cell transplant. The use of an infusion pump for peripheral blood stem cell infusion is safe, provides a reliable and consistent infusion method, and can mitigate the effect of the type of venous access line used.

Introduction: Patients (pts) with aggressive B-cell lymphomas who are relapsed or refractory to frontline therapy are typically treated with regimens including R-ICE (rituximab, ifosfamide, carboplatin, etoposide) followed by autologous stem cell transplant (ASCT) in responding pts. A minority of pts are cured with this approach, and the majority have poor outcomes. Selinexor is an oral, selective inhibitor of nuclear export, which activates tumor suppressor proteins and blocks translation of proteins that can contribute to chemoresistance, including MYC and BCL2. We conducted a phase I trial of selinexor plus R-ICE in pts with relapsed/refractory aggressive B-cell lymphomas. Methods: This phase I study used a 3+3 design with dose expansion. Eligible pts had diffuse large B-cell lymphoma (DLBCL), double hit lymphoma (DHL), and indolent lymphoma transformed to DLBCL. Treatment with 1 prior regimen administered with curative intent was required. Central nervous system (CNS) involvement was excluded. A separate cohort enrolled pts with Richter's transformation (RT) from chronic lymphocytic leukemia; there was no requirement with regard to prior therapies for this group. Selinexor was initially dosed at 40 mg (DL-1), 60 mg (DL1) and 80 mg (DL2) on days (d) -5, -3, 1, 3, and 5 and R-ICE on d1-3 of a 21-d cycle. Because of CNS toxicity thought to be primarily related to ifosfamide, the protocol was amended so that R-ICE was given on d1-3 and selinexor following completion of ifosfamide on d3, 5, and 7 of each cycle. After 2 cycles, responding pts were eligible to receive SCT or chimeric antigen receptor (CAR) T-cell therapy at discretion of treating physician. Dose limiting toxicity (DLT) period was cycle 1 and included grade (gr) 4 febrile neutropenia; gr 4 neutrophils for ≥7d; gr 4 platelets for ≥10d; gr 3 nausea, vomiting, diarrhea, or fatigue lasting >3d; or gr ≥3 non-hematologic toxicities except alopecia, fatigue or electrolyte abnormalities correctable with supportive care. Results: 22 pts enrolled with median age 67 (range 34-79). 64% were male and 36% female. Stage was III-IV in 72%. IPI was intermediate to high risk in 77%. Diagnosis was DLBCL NOS in 12, DHL in 4, transformed indolent lymphoma in 2, primary mediastinal large B-cell lymphoma in 1, and RT in 3. 7 pts were treated on the initial dosing schedule. In the first group at DL1, 0/3 pts had DLT. At DL2, 2/2 pts had DLT (gr 3 altered mental status, AMS). In the second group at DL1, 1/2 pts had DLT (gr 3 AMS). The dosing schedule was then modified as noted above. 12 DLBCL pts were treated on the modified dosing schedule. At DL1, 2/3 pts had DLT (gr 5 sepsis, gr 4 platelets ≥10d). At DL-1, 1/6 pts had DLT (gr 3 abdominal infection). Selinexor 40 mg was declared the recommended phase 2 dose (RP2D) and 3 pts were enrolled in an expansion. 3 pts with RT were treated on the modified dosing schedule; 2 received selinexor and neither had DLT at DL1. Median number of cycles of selinexor plus R-ICE was 2 (range 1-3). Most common gr 3-4 toxicities were cytopenias and hyponatremia. Most common non-hematologic toxicities of all grades were hyponatremia, fatigue, transaminitis, and nausea. Of 21 pts who received selinexor plus R-ICE, objective response rate (ORR) was 71% with 7 complete responses (CR), 8 partial responses (PR), and 3 stable disease (SD). 5 underwent SCT (3 autologous, 2 allogeneic) and 8 received CAR T-cells. Those who underwent transplant have not required additional therapy to date. 4 complete responders did not receive ASCT in part related to difficulty mobilizing stem cells; 3 have not required additional therapy with follow up of 26, 46, and 46 months. At the RP2D in the DLBCL cohort (n=9), ORR was 78% with 4 CR, 3 PR, and 2 SD. Conclusions: We report the first data on the combination of selinexor, which is now FDA-approved as a single agent in relapsed/refractory DLBCL, and chemotherapy in pts with aggressive B-cell lymphomas. We identified a dosing schedule of selinexor with R-ICE (40 mg on d3, 5, and 7) that is worthy of further study based on initial efficacy, with attention to CNS toxicity and impact on stem cell collection. Disclosures Rutherford: Karyopharm: Consultancy, Research Funding; Regeneron: Research Funding; Seattle Genetics: Consultancy; LAM Therapeutics: Research Funding; Kite: Consultancy; Juno: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Dova: Consultancy; Genentech/Roche: Research Funding; Heron: Consultancy. Allan:Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria. Ruan:Celgene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Kite Pharma: Consultancy; Juno: Consultancy; BMS: Consultancy, Research Funding. Furman:Oncotarget: Consultancy; Loxo Oncology: Consultancy; Verastem: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Incyte: Consultancy; Janssen: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Sunesis: Consultancy; Pharmacyclics: Consultancy. Cerchietti:BMS: Research Funding. Gergis:Incyte: Speakers Bureau; Merck: Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Kite: Speakers Bureau; Mesoblast: Other: Ad Board; Jazz: Other: Ad board, Speakers Bureau. Leonard:Regeneron: Consultancy; BMS/Celgene: Consultancy; Roche/Genentech: Consultancy; Epizyme: Consultancy; Bayer: Consultancy; Gilead/Kite: Consultancy; Karyopharm: Consultancy; GenMab: Consultancy; ADC Therapeutics: Consultancy; AstraZeneca: Consultancy; MEI Pharma: Consultancy; Sutro: Consultancy; Miltenyi: Consultancy. Martin:Bayer: Consultancy; Beigene: Consultancy; Kite: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy; Sandoz: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; I-MAB: Consultancy.

Background: Daratumumab (DARA) is a monoclonal antibody which targets CD38 on plasma cells and B cell progenitors. DARA has been effectively combined with other therapies in newly diagnosed and relapsed/refractory multiple myeloma (RRMM), while DARA-based induction regimens in transplant-eligible patients (pts) are increasingly being used in clinical practice. Given that hematopoietic stem cells also express CD38, DARA may potentially affect stem cell mobilization and hematopoietic reconstitution following autologous stem cell transplant (ASCT). Although no clinically significant impact of DARA on stem cell mobilization or hematopoietic recovery was described in large phase 3 trials of triplet induction regimens +/- DARA in newly diagnosed MM, stem cell yields were lower and plerixafor more commonly used in the DARA-containing arms [Moreau et al, Lancet 2019; Voorhees et al, Blood 2020]. Significantly longer time to neutrophil (PMN) engraftment was also reported in pts receiving DARA-based induction who underwent upfront ASCT [Al Saleh et al, Am J Hematol 2020]. In this study, we examine the impact of timing of DARA administration pre-mobilization on day 4 pre-harvest peripheral blood CD34 cell count, stem cell apheresis yield, and post-ASCT engraftment. Methods: Between 1/1/2016 and 12/31/2019, newly diagnosed and RRMM pts receiving DARA-based induction regimens with ≥1 dose of DARA administered within 1 month prior to stem cell mobilization were identified retrospectively and compared to matched controls receiving similar induction regimens without DARA. Granulocyte colony-stimulating factor (G-CSF) was administered per institutional standards and plerixafor added based on day 4 pre-harvest peripheral blood CD34 counts. PMN and platelet engraftment post-ASCT was defined as the first of 3 consecutive days with sustained PMN count >500 x 106/L and independence from platelet transfusion in the preceding 7 days with a count >20 x 109/L, respectively. Pre-harvest peripheral blood CD34 counts and stem cell apheresis yields were obtained from the Cellular Therapy Laboratory at NewYork-Presbyterian Hospital. The study was approved by the Weill Cornell Medicine IRB. Results: We identified 16 pts who received DARA-based induction with ≥1 dose of DARA administered within 1 month of apheresis (DARA group) and 16 non-DARA-containing regimen-matched controls (non-DARA group). Demographics of the DARA and non-DARA groups were well matched (Table 1). DARA pts received their last dose of DARA a mean of 17.3 days prior to the first day of apheresis, with 8 pts receiving their last dose within 2 weeks and the remaining 8 pts between 2 weeks and 1 month prior. Overall, mobilization outcomes were inferior in the DARA group (Table 2). DARA pts had significantly lower day 4 pre-harvest peripheral blood CD34 counts compared to non-DARA pts (17.2 vs 35.4 cells/µL; P=0.0146). Institutional algorithm required plerixafor to be given for day 4 CD34 count ≤40 cells/µL. Fifteen of the 16 DARA pts received plerixafor vs. 11 non-DARA pts (P=0.07). Additionally, DARA pts required significantly more apheresis days (2.4 vs 1.6 days; P=0.0279). Differences in stem cell yield were not significant (8 vs 10 x106cells/kg; P=0.1391). Hematopoietic recovery post-ASCT was not affected by DARA administered in the month preceding mobilization. Conclusions: In summary, we report lower day 4 pre-harvest peripheral blood CD34 count, increased requirement for plerixafor, and longer apheresis duration in newly diagnosed and RRMM pts receiving DARA within 1 month ofstem cell mobilization. These limitations are largely overcome by plerixafor usage which, combined with G-CSF, resulted in successful stem cell collection in all patients. Limitations in our study include small sample sizes, retrospective control selection, and fewer pts in the DARA group achieving ≥VGPR prior to mobilization. Nevertheless, our findings are consistent with inferior mobilization outcomes reported in the DARA-containing arms of phase 3 trials of triplet induction +/- DARA and highlight the nearly universal requirement for plerixafor usage when DARA is administered within a month prior to apheresis. Prospective study of day 4 pre-harvest peripheral blood CD34 counts and other predictors of stem cell yield should be incorporated into future clinical trials of CD38 monoclonal antibody-based induction regimens for transplant-eligible MM pts. Disclosures Rossi: Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Niesvizky:GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Rosenbaum:Amgen: Research Funding; GlaxoSmithKline: Research Funding; Akcea: Honoraria; Celgene: Honoraria; Janssen: Research Funding.

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia. Of the three cases of AML found in TAR patient, only one was reported in an adult. We report a case of myelodysplastic syndrome progressing to AML with calreticulin driver mutation in an adult male with TAR syndrome who was successfully treated with hematopoietic allogeneic stem cell transplantation.

Natural killer (NK) cell recognition and killing of target cells are enhanced when inhibitory killer immunoglobulin-like receptors (KIR) are unable to engage their cognate HLA class I ligands. The genes of the KIR locus are organized into either KIR B haplotypes, containing 1 or more activating KIR genes or KIR A haplotypes, which lack those genes. Analysis of unrelated donor (URD) hematopoietic cell transplants (HCT), given to acute myeloid leukemia (AML) patients between 1988 and 2009, showed that KIR B haplotype donors were associated with better outcomes, primarily from relapse protection. Most of these transplants involved marrow grafts, fully myeloablative (MAC) preparative regimens, and significant HLA mismatch. Because the practice of HCT continues to evolve, with increasing use of reduced intensity conditioning (RIC), peripheral blood stem cell grafts, and better HLA match, we evaluated the impact of URD KIR genotype on HCT outcome for AML in the modern era (2010-2016). This analysis combined data from a prospective trial testing URD selection based on KIR genotypes (n = 243) with that from a larger contemporaneous cohort of transplants (n = 2419). We found that KIR B haplotype donors conferred a significantly reduced risk of leukemia relapse and improved disease-free survival after RIC, but not MAC HCT. All genes defining KIR B haplotypes were associated with relapse protection, which was significant only in transplant recipients expressing the C1 epitope of HLA-C. In the context of current HCT practice using RIC, selection of KIR B donors could reduce relapse and improve overall outcome for AML patients receiving an allogeneic HCT.

Relapse remains the major cause of death in older patients transplanted for acute myeloid leukemia (AML) in first complete remission or for patients with advanced myelodysplastic syndrome (MDS) at any age. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with reduced-intensity conditioning when performed in younger patients with AML or MDS, but the toxicity of this approach in older patients is prohibitive. We hypothesized that pharmacokinetic targeting to optimize busulfan (BU) exposure, combined with the administration of azacitidine (AZA) post-transplant would mitigate the risk of relapse while reducing nonrelapse mortality and ultimately improve progression-free survival (PFS). On this phase II multicenter study, 63 patients (40 unrelated donors and 23 matched related donors) received a uniform conditioning regimen consisting of fludarabine i.v. (days –7 to –3), BU targeted to a daily area under the curve (AUC) of 4000 μM/min (days –6 to –3) after the administration of a 25-mg/m2 i.v. test dose on 1 day between days –14 to –9, and antithymocyte globulin (days –6, –5, and –4 (2 doses for matched related donors and 3 for matched unrelated donors only). Beginning on days +42 to +90, all patients were planned to receive up to 6 monthly cycles of AZA at 32 mg/m2 subcutaneously for 5 days. The median age was 62 years (range, 44 to 74); 13 had AML and 50 had MDS; 87% of patients were within 20% of the target AUC based on a validation sample. Forty-one patients (65%) started AZA at a median of 61 days (range, 43 to 91) post-transplant, and 17 patients (41%) completed all 6 cycles of AZA. The cumulative incidence of nonrelapse mortality at 2 years was 33.4% (95% confidence interval [CI], 22%-45%). The cumulative incidence of relapse was 25% (95% CI, 15%-37%) at 2 years. With a median follow-up of 58.9 months, the estimated PFS probability at 2 years and 5 years after transplantation was 41.2% (80% CI, 33.9%-49.9%) and 26.9% (80% CI, 20.4%-35.5%), respectively, for the entire group with a median PFS of 15.8 months (95% CI, 6.7 to 28.3). The probability of overall survival at 2 and 5 years was 45.7% (95% CI, 34.9%-59.9%) and 31.2% (95% CI, 21.3% to 45.8%), respectively, for the entire group with a median overall survival of 19.2 months (95% CI, 8.7 to 37.5). In summary, we demonstrated the feasibility of a novel reduced-intensity conditioning regimen with test dose BU targeted to an AUC of 4000 μM/min. The feasibility of AZA in this setting appears to be limited if applied to an unselected population of older hematopoietic stem cell transplantation recipients. (ClinicalTrials.gov Identifier: NCT01168219.)

BackgroundDiarrhea is common and associated with substantial morbidity among hematopoietic cell transplant (HCT) recipients, but the etiology is often not identified. Multiplexed polymerase chain reaction (PCR) assays increase the detection of diarrheal pathogens, but the impact of this technology in this population has not been evaluated.MethodsOur center replaced stool cultures and other conventional microbiologic methods with the FilmArray Gastrointestinal Panel (GI PCR) in June 2016. We reviewed all adult patients who received an HCT from June 2014–May 2015 (pre–GI PCR, n = 163) and from June 2016–May 2017 (post–GI PCR, n = 182) and followed them for 1 year after transplantation. Clostridioides difficile infection was diagnosed by an independent PCR test in both cohorts.ResultsThe proportion of patients with ≥1 identified infectious diarrheal pathogen increased from 25% to 37% after implementation of GI PCR (P = .01). Eight patients (5%) in the pre–GI PCR cohort tested positive for a pathogen other than C. difficile versus 49 patients (27%) in the post–GI PCR cohort (P < .001). The most common non–C. difficile diarrheal pathogens in the post–GI PCR cohort were enteropathogenic Escherichia coli (n = 14, 8%), norovirus (n = 14, 8%), and Yersinia enterocolitica (n = 7, 4%). The percentage of diarrheal episodes with an identified infectious etiology increased from 14% to 23% (P = .001). Median total costs of stool testing per patient did not increase (pre: $473; post: $425; P = .25).ConclusionsInfectious etiologies of diarrhea were identified in a higher proportion of HCT recipients after replacing conventional stool testing with a multiplexed PCR assay, without an increase in testing costs.

High-dose melphalan (MEL200) followed by autologous stem cell transplantation (ASCT) remains a standard of care for multiple myeloma (MM). Bendamustine induces responses in MM resistant to other alkylators. Our prior Phase I trial adding bendamustine to MEL200 transplant conditioning resulted in no additional toxicity. We now report a single-arm, phase II study that evaluated the efficacy of bendamustine 225 mg/m

Background Preliminary evidence indicates that the addition of low-dose total body irradiation (TBI) (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high-risk patients receiving combination haploidentical single-unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. Methods We retrospectively reviewed the posttransplant outcomes of patients who underwent haplocord stem cell transplant between May 2013 and March 2015 and who received fludarabine 30 mg/m day (D)-7 to -3, melphalan 140 mg/m D-2, and 2 Gy TBI D-4 and -3. Results All 25 patients achieved primary neutrophil engraftment after a median of 12 days. The median time to platelet engraftment was 27 days. The cumulative incidence of nonrelapse mortality was 16% by D+100 and 33% by 1 year. The cumulative incidence of grade III to IV acute graft-versus-host disease was 36% by D+100. The CIR was 13% by D+100 and 29% by 1 year. The estimated 1-year overall survival and progression-free survival were 40% and 37%, respectively. In a subgroup analysis, we compared the outcome of 13 acute myeloid leukemia patients receiving this conditioning regimen with age and disease risk index-matched acute myeloid leukemia patients receiving fludarabine-melphalan without TBI. The TBI group had lower incidence of relapse at 1 year (15% vs 54%, P = 0.05). Conclusions Overall, combination fludarabine-melphalan with low-dose TBI after haplocord stem cell transplant assures good engraftment and leads to acceptable toxicity and disease control in the setting of high risk, heavily pretreated patients. These findings warrant further investigation at a larger-scale, prospective level.

Human herpes virus type 6 can reactivate in patients after allogeneic stem cell transplantation and has been associated with serious sequelae such as delayed engraftment and an increased risk of developing acute graft-versus-host disease (GVHD). This study investigated human herpes virus type 6 (HHV-6) reactivation within 60 days of transplantation in stem cell transplants utilizing single umbilical cord blood, double umbilical cord blood, or umbilical cord blood plus haploidentical stem cells. Of 92 patients, 60 (65%) had HHV-6 reactivation. Reactivation was not significantly influenced by any patient characteristics, disease characteristics, or by stem cell source (umbilical cord blood only versus haploidentical plus umbilical cord blood). We did not observe any impact of HHV-6 reactivation on neutrophil or platelet count recovery or on relapse-free survival. HHV-6 reactivation was associated with subsequent development of prerelapse acute GVHD (HR = 3.00; 95% CI, 1.4 to 6.4; p = 0.004).

Background: As one of the most prevalent pathogens in the environment, influenza affects millions of patients annually and contributed to tens of thousands of deaths in the United States during 2018-2019 alone. Immune deficiency is one of the most significant risk factors for adverse outcomes in adults with influenza, and similarly infectious complications are one of the most common causes of death in hematopoietic stem cell transplant (HSCT) recipients. However, data on outcomes or risk factors for progression in influenza infections specifically in HSCT recipients are limited. Methods: We reviewed patient demographics, oncology and transplant history from HSCT recipients with polymerase chain reaction (PCR)-confirmed influenza over 5 influenza seasons (from 2013-2014 through 2018-2019). Influenza subtype (A H1, H3, and B), laboratory studies at diagnosis, treatments, vaccination status, and outcomes for each influenza infection were recorded and analyzed. Results: A total of 143 infection events were collected and analyzed for symptoms and outcomes. Influenza infections of each subtype occurred in each season, although a different strain predominated each season. The most common symptoms at presentation were cough (65.3%) and fever (55.2%). Symptoms at presentation and outcomes were not significantly different amongst Influenza type A H1, A H3 and type B infections (p>0.05). In total, 22 (15.4%) infections presented as lower respiratory tract infections (LRTIs) and 7 additional infections progressed to LRTIs (all LRTI: 29; 20.1%). 63 (44.1%) infected patients required hospital admission, 15 (10.5%) required transfer to the intensive care unit (ICU) and 8 (5.6%) were intubated. 6 patients (4.2%) died by 30 days after the initial positive test, and 23 (16.1%) died by 180 days. LRTI was significantly associated with hospital admission (p0.05) or intubation (p>0.05). No other factors were significantly associated with LRTI, including vaccination status or treatment with antivirals (p>0.05). Logistic regression analysis of selected factors found that patients receiving steroids were significantly associated with LRTI (OR 2.58: 95% CI 1.00-6.63; p=0.047) (Table 1). There was, however, no statistically significant association detected between active graft-versus-host disease and LRTI (OR 1.25: 95% CI 0.35-4.06; p=0.721). We also found that treatment with oseltamivir within 2 days of symptom onset was not significantly associated with LRTI (OR 1.42: 95% CI 0.59-3.49; p=0.431). Persistent shedding (positive tests longer than 21 days from initial positive test) was also not associated with adverse outcomes (p>0.05). Conclusion: This study suggests that the use of chronic steroids in treatment for graft-versus-host disease in HSCT patients may increase the risk for adverse outcomes in influenza infections. Disclosures No relevant conflicts of interest to declare.

Background Limited data are available for risk assessment and outcome of COVID-19 in patients with hematologic malignancies (HM). We present a single center study of COVID-19 pneumonia in a cohort of 31 patients with HM. Methods Data were abstracted from electronic medical records for patients admitted to NYPH between 3/5/20 and 4/17/20 and entered into a REDCap database. Results Twenty (64.5%) were male; median age was 71 years. There were 8 patients with Multiple Myeloma (MM), 8 with Chronic Lymphocytic Leukemia (CLL), 6 (19.4%) had AML, 5 (16.1%) NHL, 2 (3.2%) ALL; CML, MDS and Polycythemia Vera occurred in 1 patient each. Twenty-four (77.4%) had active HM; 6 (19.4%) were in remission; and 1 relapsed. Nineteen patients (61.3%) received recent chemotherapy and 11 (35.5%) immunosuppressive therapies. There were 7 (22.6%) hematopoietic stem cell transplant (HSCT) recipients (4 allogeneic and 3 autologous). Comorbidities were evenly distributed among all malignancies: 18 (58.1%) had hypertension, 9 (38.7%) obesity, 7 (22.6%) diabetes mellitus, and 11 (35.5%) were former smokers. The most common symptoms included cough (90.3%), fever (83.9%) and dyspnea (61.3%); 7 (22.6%) had nausea and vomiting; 7 (22.6%) had diarrhea. On presentation, hypoxia (O2 sat ≤94% on room air) occurred in 64.5%; median ALC was 330/ml; 23 (74.2%) had ALC< 1000/ml; median CRP was 15.9 mg/dl (2.5–40.4), ferritin 1162 ng/ml (264 - > 16500), and D-dimers 456 ng/ml (< 150–2418). Thirteen patients (41.9%) required ICU admission and were intubated; among those 9 (69.2%) had either MM or CLL. Co-infections were uncommon; two patients developed HSV1 pneumonitis and one of these also had CMV pneumonitis. Twenty-eight (90.3%) were treated with hydroxychloroquine, 5 (16.1%) remdesivir, 2 (6.5%) tocilizumab, 1 (3.2%) sarilumab, and 4 (12.9%) with methylprednisolone 0.5mg/kg Q12h. Seventeen patients (54.8%) recovered and were discharged, 12 (38.7%) died; 2 (6.5%) were still hospitalized but left the ICU. Conclusion In our cohort, there were predominantly more patients with MM and CLL and 56% of these were intubated; larger cohort studies will further define the risk and outcome for COVID-19 in patients with HM. Disclosures Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Grant/Research Support)Merck (Grant/Research Support)Shionogi Inc. (Consultant)

Introduction Haplo-cord transplantation – the co-infusion of a single cord unit with CD34-selected cells from a haplo-identical donor, provides an alternate stem cell source for patients lacking HLA-matched donors. Anti-thymocyte globulin (ATG) is routinely used in haplo-cord preparative regimens to reduce graft failure, graft vs. host disease (GVHD) and graft vs. graft reactions. However, excessive depletion of cord lymphocytes may compromise immune reconstitution and graft vs. tumor (GVT) effects. Methods We reviewed lymphocyte recovery and outcome data for consecutive patients with hematologic malignancy who underwent haplo-cord transplantation at Weill Cornell Medicine between June 2012 and June 2019. All were conditioned using fludarabine and melphalan with or without total body irradiation (200-600cGy). All received rabbit ATG (Thymoglobulin), initially at a total dose of 6mg/kg (2012-2013) and later at a total dose of 4.5mg/kg (2013 onward). Data was collected as part of study 01810588 registered at clinicaltrials.gov. Probabilities of relapse and non-relapse mortality (NRM) were generated using cumulative incidence estimates to accommodate competing risks. Probabilities of overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. Results Our study included 220 haplo-cord transplant recipients with a median age of 58 yrs (Range: 18 – 76 yrs). The majority had myeloid disease (AML – 54%, MDS/MPN – 19.5%, CML – 2%). Conditioning incorporated TBI for 120 patients (55%). ATG was dosed at 6mg/kg for 41 patients (19%). The median absolute lymphocyte count (ALC) at first ATG exposure was 0.4 × 10^9/L (IQR25-75: 0.2-0.7 × 10^9/L). The median patient weight was 75.5kg (IQR25-75: 65.4-89.9kg). Neutrophil and platelet engraftment occurred at a median of 12 days (IQR25-75: 10-16 days) and 22 days (IQR25-75: 17-35 days) respectively. Graft failure was observed in 16 patients (7%). Rapid early recovery of CD19+ lymphocytes, CD56+ natural killer cells and IgG levels was observed. T-cell recovery was delayed, with a gradual increase observed from Day 100 (Figure). Overall PFS and OS at 2 yrs were 30% (CI 24-37%) and 39% (CI 32-46%) respectively. The 2 yr cumulative incidence of NRM was 33% (+/- 3% SEM). The overall 2 yr incidence of relapse was 37% (+/- 3% SEM), however there was a significant difference in relapse incidence between patients treated with 6mg/kg ATG (54%) versus 4.5mg/kg (31.5%) (p=0.009). Conclusion Haplo-cord transplant facilitates early neutrophil engraftment with early normalization of B- and NK-lymphocytes. An observed delay in T-cell recovery may be due to the use of ATG in this platform and higher ATG doses result in a greater incidence of relapse. Our data supports the minimization or replacement of ATG in haplo-cord transplant. An analysis of GVHD incidence and viral reactivation events is ongoing and will be presented.

Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Unlike other respiratory viruses, little is known about the clinical significance of human coronavirus infection (HCoV) in this population. We retrospectively identified all HSCT recipients who were transplanted between May 2013 and June 2017 at our institution and characterized the cumulative incidence of post-transplant HCoV infection. Of 678 patients who underwent HSCT during the study period, 112 (17%) developed HCoV infection, making HCoV the fourth most common respiratory viral infection. Thirty-four (30%) HCoV-infected patients progressed to proven or probable lower respiratory tract infection (LRTI). Age ≥50, graft-versus-host disease, corticosteroids, hypoalbuminemia, and inpatient status at the time of infection were independently associated with progression to LRTI. Twenty-seven (59%) patients who underwent repeat NP swab had persistent viral shedding for ≥21 days, with a median duration of 4 weeks of viral shedding. We conclude that HCoV is common and clinically significant in HSCT recipients, with nearly one-third of patients progressing to proven or probable LRTI. Evaluating for LRTI risk factors found in this study may identify patients who require closer surveillance and aggressive supportive care when infected with HCoV.

Donor-specific HLA antibodies (DSAs) have been associated with an increased risk of graft failure. To decrease DSA levels and reduce the risk of graft failure in haploidentical cord blood transplantation recipients, we studied the effect of bortezomib (BTZ) and i.v. immune globulin (IVIG) pretransplantation. Between 2012 and 2016, 14 patients with a DSA level >2000 mean fluorescence intensity (MFI) to 1 or more mismatched HLA alleles of haploidentical donors, cord blood donors, or both were treated with BTZ and IVIG. Fourteen patients received a median of 4 doses (range, 2 to 8 doses) of BTZ 1.3 mg/m2 and a median total IVIG of 2 g/kg before transplantation. Only 2 of 14 patients attained a reduction in MFI to

BACKGROUND: Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. METHODS: From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for β-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. RESULTS: We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P < .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. CONCLUSIONS: HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.

Background Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX prophylaxis is widely used. Methods We performed a single-center, retrospective case series of HSCT recipients from January 1, 2012 to December 31, 2018. Subjects had clinical symptoms and radiographic evidence for PJP along with at least one positive Pneumocystis test obtained from bronchoalveolar lavage (BAL) including direct fluorescence antibody (DFA), quantitative polymerase chain reaction (qPCR), cytology, and pathology. Results 1111 subjects underwent HSCT; of whom, 25 (2.2%) met inclusion criteria and were treated for PJP. 6 were autologous and 19 were allogeneic HSCT recipients (1.23% and 3.05% of total autologous and allogeneic HSCT, respectively). All allogeneic HSCT recipients received in-vivo T-cell depletion. Median duration from autologous and allogeneic HSCT to PJP diagnosis were 138 days (range 20 to 348) and 346 days (range 41 to 771), respectively. PJP qPCR was positive in all samples tested (n = 20, range < 84 to 14900). DFA was positive in 6 (28%). Death from pneumonia occurred in 2 subjects; 11 (44%) required ICU stay, and 7 (27%) required intubation. At diagnosis, 3 subjects had relapse of underlying disease and 10 were on immunosuppression. 12 were on PJP prophylaxis (autologous HSCT n = 3), the most common of which was atovaquone (n = 5); only 2 subjects were on TMP-SMX. Cytomegalovirus (CMV) viremia was detected in 9 subjects (36%) prior to PJP diagnosis; 4 had pulmonary CMV coinfection. In total, 17 subjects (68%) had one of the above risk factors for PJP. Median total lymphocyte count and % lymphocytes were 5.1 × 103 cells/μL (range 1.4 to 38.5 × 103 cells/μL) and 9.6% (range 1.1 to 29.5%), respectively. Conclusion PJP is an uncommon (2.2% of the study population) complication of HSCT while receiving PJP prophylaxis and in the absence of disease relapse, CMV reactivation, or ongoing immunosuppression. Presentation is often delayed in this population; a high degree of clinical suspicion should prompt diagnostic evaluation using a combination of laboratory tests on BAL fluid. Disclosures All authors: No reported disclosures.