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Introduction Mutations at diagnosis in acute myeloid leukemia (AML) patients have prognostic implications. For AML patients undergoing allogeneic stem cell transplant (SCT), the prognostic impact of molecular mutations pre-transplant and immediately post-transplant are less well characterized. Here we examine the mutation status of AML patients at different time points in relation to allogeneic SCT and their implications in relapse and survival. Methods A total of 110 AML patients who underwent allogeneic SCT after achieving complete remission with available molecular mutation testing at diagnosis, prior to transplant (within 4 weeks), and 28 days post-transplant from 2014-2018 were included in the analysis. Multivariable cox regression analysis was adjusted for age, gender, CIBMTR disease risk index (DRI), type of transplant, and genetic mutation. Backward selection method was used to select the best combination of genes that is associated with OS and relapse-free survival (RFS). Results With a median follow-up time of 31.6 month, the median overall survival for the cohort was 37.1 months. Eighty-one patients had molecular testing at diagnosis. 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 RFS, but not OS on multivariate analysis. Seventy-seven patients had molecular testing prior to transplant and 27 patients had persistent mutations. The presence of mutations in ETV6 and FLT3-ITD were independently associated with worse RFS ((HR 49.7, p=0.001, CI 5.0-528) & (HR 36.4, p NRAS mutations was associated with worse RFS (HR 105, p=0.0004, CI 8.1-1350), but not OS. Mutations in TP53 were associated with worse RFS (HR 70.97, p=0.0026 CI 4.44-1135) and OS on univariate (HR 9.82, p=0.0327, CI 1.21-79.82), but not on multivariate analysis. At 28 days post-transplant, only 9 of the 84 patients had persistent mutations. Persistence of FLT3-ITD conferred worse RFS and OS in both univariate ((HR 11.92, p=0.0218, CI 1.43-98.98) & (HR 25.16, p=0.0052, CI 2.62, 241.92)) and multivariate ((HR 18.13, p=0.0089, CI 2.07-158.86) & (HR 35.47, p=0.0028, CI 3.41-368.81)) analysis. Conclusions Persistent presence of mutations in ETV6 and FLT3-ITD prior to stem cell transplant and mutations in FLT3-ITD at day 28 post-transplant were associated with poor RFS and OS. This analysis further supports association of adverse outcomes in AML patients with selected persistent mutations prior to stem cell transplant. Utility of serial mutation testing prior to transplant should be further investigated in prospective studies.

Background Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. Objectives This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. Study design From April 2012–March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. Results One hundred and ten HM patients presented with HRV URTI (n = 78) and HRV LRTI (n = 32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0–9.2; p = 0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. Conclusions HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.

Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 to May 2006) and after (June 2006 to April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49 of 119) to 14.7% (23 of 156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < .001, for each). In contrast, rates of BSI (43.1% versus 47.3%; P = .50) and FN (98.8% versus 97.1%; P = .63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio, .27; 95% confidence interval, .14 to .51; P < .001) and FN (odds ratio, .18; 95% confidence interval, .09 to .36; P < .001) in multivariate analysis. Patients with myeloma had a nonsignificant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% versus 1%, P = .08) and Clostridium difficile infection (7% versus 3%, P = .12) after the initiation of levofloxacin prophylaxis but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT.

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected

BACKGROUND The collection of autologous peripheral blood (PB) stem cells can be challenging in the subgroup of patients deemed “poor mobilizers” with granulocyte–colony-stimulating factor. Plerixafor, a CXCR-4 antagonist, is an alternative mobilizing agent, but is costly, and the optimal mobilization algorithm has yet to be determined. STUDY DESIGN AND METHODS To address the question we developed a protocol measuring PB CD34 on Day 4 of mobilization. We examined 26 patients before initiating the protocol versus 24 patients after initiation. RESULTS Significant differences (p ≤ 0.05) included fewer days of collection (1.25 days vs. 2.42 days), lower total blood volume processed (25.9 L vs. 57.2 L), lower total product volume (324 mL vs. 691 mL), lower RBC content (9 mL vs. 18 mL), and lower granulocyte percentage per collection (35% vs. 11%). There were no significant differences between the two groups in demographics, baseline platelet count, total CD34, or CD34/kg harvested. CONCLUSION Use of a protocol to assess PB CD34 1 day before collection allows for preemptive administration of plerixafor to augment mobilization. Subsequently, days of collection and processed blood volume are reduced while there is less RBC and granulocyte contamination in the collected stem cell product.

Dextran 40 is the main component of the solution used to wash or dilute thawed cord blood unit (CBU) products for stem cell transplant. Dextran 40 became unavailable in the United States as of April 2014. Like many other cellular therapy laboratories in the United States, we found ourselves with limited dextran 40 inventory, a growing CBU transplant requirement, and no alternative solution. Since there are no published alternative washing solutions for cryopreserved CBU we had to develop and validate a new solution rapidly. We chose to validate hydroxyethyl starch (HES) due to its similar ability to stabilize red blood cells and reduce sudden changes in osmolality that occur during thawing. For the validation we used 3 CBUs and thawed and washed each unit with both dextran 40- and HES-based solutions; thus, each CBU served as its own control. We observed no significant differences between the two wash solutions for all the monitored variables including cell viability, cell recovery, or potency measured by colony-forming cell assay. Based on this initial validation we began using HES-albumin for CBU washing after our supply was exhausted. Our initial experience with the first 16 CBU transplants after validation indicates safe infusion and preliminary cord engraftment.

Hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life‐threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi‐organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded‐access treatment programme (T‐IND; {"type":"clinical-trial","attrs":{"text":"NCT00628498","term_id":"NCT00628498"}}NCT00628498). In the completed T‐IND, the Kaplan–Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7–61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (≤21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8–71·6%) and 47·1% (95% CI, 42·3–51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T‐IND study was similar to previous reports.

Introduction: Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT. Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome. Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies. Methods: All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy. Results: A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1. Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine. Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin. All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy. Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3. Conclusions: Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. Download : Download high-res image (217KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Introduction: CAR T therapy has improved overall survival for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who otherwise have poor outcomes with traditional chemoimmunotherapy. Cytokine release syndrome (CRS) and neurotoxicity are well known side effect from CAR T therapy. Cytopenia has been reported as well. However, to our knowledge, transfusion requirements during the first 30 days post-CAR T treatment have not been reported. Here we report the cytopenia characteristics and transfusion requirements in 15 patients who received commercial Axicabtagene ciloleucel (Yescarta) CAR-T cell therapy. Methods: We retrospectively reviewed all DLBCL patients who received Yescarta between July 2018 through May 2019 at Weill Cornell Medical Center. All patients received cyclophosphamide (500mg/m2) and fludarabine (30mg/m2) lymphodepleting regimen from days -5 to -3 before the CAR T cell infusion. Cytopenia, granulocyte-colony stimulating factor (G-CSF) use, packed red blood cell (RBC) and platelet transfusion requirements during 30 days after CAR T infusion were examined. Cytopenia was defined according to CTCAE criteria. Grade 3 cytopenia was white blood cell (WBC) Results: Median age was 68 years (range, 21-86yr) with 53% males (Table 1). Ten patients (67%) experienced cytokine release syndrome (CRS) with 8 patients receiving at least 1 dose of tocilizumab. Five patients (33%) experienced immune cell-associated neurologic syndrome (ICANS) and all received dexamethasone. Among patients with ICANS, one required ventilation support, one had a focal seizure and one had cerebellar ischemic stroke. Ten (70%) of the 14 evaluable patients had a D30 restaging PET/CT. Two patients had progressive disease and12 patients achieved partial response (PR). On admission, grade 3 or 4 leukopenia or neutropenia was observed in 0 patients, except 1 patient (WBC14.1, but ANC 0). There were 2 patients had grade 3 anemia, none of the patients had grade 4 anemia or grade 3/4 thrombocytopenia. Between D0 and D30, grade 3 or 4 leukopenia or neutropenia was observed in 12 patients (Figure 1). Grade 3 or 4 anemia was observed in 6 and 5 patients and grade 3 or 4 thrombocytopenia in 9 and 6 patients respectively. A total of 6 patients (43%) required G-CSF, 6 (43%) and 6 (43%) patients required red blood cell transfusion and/or platelet transfusion support. The median PRBC and platelet transfusion was 0 (range, 0-8) and 0 (range, 0-19). Three (20%) of the 15 patients accounted for the majority of the transfusion support. Conclusion: Cytopenia was common during the first 30 days after CAR-T cell therapy. Although nearly half of the patients required G-CSF and transfusion support, few patients had a significant burden. Disclosures Van Besien: Miltenyi Biotec: Research Funding.

Background: Autologous stem cell transplantation (ASCT) performed early in the disease course or at first relapse leads to improved progression-free and overall survival in transplant-eligible patients with multiple myeloma (MM). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), when used after ASCT has been shown to accelerate time to neutrophil engraftment (TNE), and in some studies, it has been associated with reduced length of hospitalization, infectious complications, and antibiotic use. Strategies that reserve G-CSF administration to when neutrophil recovery is delayed, have attempted to show that there is no difference in infectious complications, length of hospitalization or TNE when compared to early administration of G-CSF on the day after stem cell infusion (DOT). However, the optimal timing for administering G-CSF has not yet been determined in patients with MM undergoing ASCT. Methods: This is a retrospective, single-center analysis of patients with MM undergoing ASCT from mobilized peripheral blood stem cells. Patients enrolled in a clinical trial of high-dose lenalidomide and melphalan as conditioning therapy which mandated the administration of filgrastim from day +1 after DOT (Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma, NCT01054196) were assigned to the early strategy group (ES). Patients receiving filgrastim as per our institutional guideline (starting on day +12 if ANC < 1000 cells/uL, or at the physician's discretion) were included in the delayed strategy group (DS). Patients were excluded from the analysis if their conditioning regimen included a different agent other than melphalan or lenalidomide. DOT was defined as the day of stem cell infusion. Date of neutrophil engraftment was defined as the first of three consecutive days with an ANC ≥ 500 cells/uL. TNE was calculated as the time from DOT to the date neutrophil engraftment. Total duration of neutropenia was defined as the time from onset of neutropenia (ANC < 500 cells/uL) to date of neutrophil engraftment. Length of hospitalization was defined as the time from DOT to the day of discharge. Results: We identified 59 patients in the ES group and 39 patients in the DS group from 08-16-2010 to 05-22-2019, for a total of 98 included in this analysis. Median age was 60 and 65 years in the ES and DS groups, respectively. Patients received a comparable dose of CD34+ cells, 5.05x106/kg in the ES group vs 4.66x106/kg in the DS group (p = 0.48). The ES group started filgrastim administration earlier (day +1 vs +9, p < 0.001) and received a greater median number of doses (10 vs 4, p < 0.001) as compared to patients in the DS group. Median time to neutrophil engraftment was shorter in the ES group compared to the DS group (10 vs 12 days, p < 0.001), as was the total duration of neutropenia (5 vs 6 days, p < 0.001). Documented infections were just as likely in both groups, 37% in the ES group and 39% in the DS group (p = 1). Length of hospitalization was shorter in the ES group as compared to the DS group (15 vs 17 days, p = 0.01). Discussion: Filgrastim use guided by an ES decreased the time to neutrophil engraftment, the duration of neutropenia and the length of hospitalization compared to a DS. Further analyses to identify predictive factors associated with a reduction in infectious complications and length of stay are underway, with the aim of developing a risk-adapted strategy for the use of filgrastim in patients with MM undergoing ASCT. Disclosures Van Besien: Miltenyi Biotec: Research Funding. Coleman:Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Rosenbaum:Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

Introduction: Predictors routinely used to assess long-term survival after allogeneic hematopoietic cell transplantation (alloHCT) have not been specifically validated for pre-transplant risk assessment of patients getting cord blood transplantation supported by Haplo-CD34+ Progenitor cells as a myeloid bridge (haplo-cord). Methods: All consecutive adult patients with hematological malignancies who received an alternative donor alloHCT with a haplo-cord at Weill Cornell Medicine were included. Data was collected from an ongoing haplo-cord protocol (clinicaltrials.gov identifier 01810588). Plasma cell disorders were excluded. Age, CIBMTR Disease Risk Index (DRI), Karnofsky performance score (KPS), and HCT comorbidity index (HCT-CI) (routinely calculated since 06/2014), were assessed before alloHCT. The Kaplan-Meier method was used to estimate OS probabilities. Comparisons of OS were evaluated by the log-rank test. Significant predictors were considered in a Cox proportional hazards regression model using forward stepwise selection. A cumulative incidence function (CI) for relapse was calculated using a competing risk model for non-relapse mortality (NRM). We further validated our findings in the subgroup of patients with AML. Results: Between 06/2012 and 12/2018, 217 patients underwent haplo-cord transplantation. Indications for alloHCT included: 66% leukemia, 19% MDS/MPN, 15% Lymphoma. Median age was 58 yr (22% ≤ 40yrs, 33% between 41-59yrs, and 45% ≥ 60 yrs). 43% of patients were women. KPS score was ≥ 90 in 56%. DRI was high/very-high in 43% and low/intermediate in 56%. HCT-CI for 154 patients was 0 in 14%, 1-2 in 21%, 3-5 in 45% and ≥ 6 in 20%. Conditioning regimens included fludarabine with melphalan 45%, plus TBI 51%, other 4%. Median follow-up was 30 months. 2yr OS was 38% (95%CI 31-44%). 2yr CI of NRM was 35% and relapse 36%. Age (p=0.001), DRI (p Conclusion: DRI and age are highly predictive of OS for patients undergoing haplo-cord transplantation. Our finding that HCT-CI is not predictive of OS when applied to haplo-cord alloHCT is supported by previous findings investigating the role of HCT-CI in cohorts with cord blood donors (Adachi Y et al BBMT 2018 and Majhail N et al BBMT 2008). To this end, our findings demonstrate that a high HCT-CI score should not preclude patients from evaluation for alternative donor transplantation using cord blood supported by Haplo-CD34+ progenitor cells. Other prognostic tools to assess specific comorbidities impacting this transplant platform are needed for accurate pre-transplant risk assessment in order to improve decision making and clinical trial assignments. Disclosures Van Besien: Miltenyi Biotec: Research Funding.

Cannabis sativa contains numerous cannabinoids, with D9-tetrahydrocannabinol (THC) and cannabidiol (CBD) the primary cannabinoids of medical interest. Both THC and CBD possess potent anti-inflammatory and immunosuppressive properties, but THC has significant psychoactive properties. In a phase 2 study of CBD plus standard GVHD prophylaxis,, Yeshrun et al found low rates of grade II - IV acute GVHD, and compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II - IV acute GVHD was .3 (P =.0002)1. Also, Kalytera Therapeutics announced promising results in a Phase 2a study evaluating the safety and efficacy of CBD, for the treatment of acute Grade III-IV GVHD, including 9/ 10 responses, of which 7 were complete remission (CR)2. We report a case of steroid refractory eczematous GVHD successfully treated with a CBD-predominant medical cannabis product. A 35 year old woman with T-cell Acute Lymphoblastic Leukemia (T-ALL) was treated on an MSKCC pediatric -inspired ALL protocol. She developed CNS involvement during induction therapy treated with intrathecal therapy with persistent CNS disease. She then received salvage therapy with HyperCVAD part B with high dose methotrexate, high dose cytarabine, with CR and underwent matched related donor (sister) stem cell transplant conditioned with Etoposide, TBI 1200 cGy. GvHD prophylaxis was Alemtuzumab, Tacrolimus. She developed a rash on day 126 post transplant involving face and scalp which spread to chest and back and within 1 week involved 100% of BSA with itching, facial and orbital swelling, ankle/feet swelling. Skin biopsy revealed an eczematous variant of GvHD which is considered to be very aggressive, difficult to control with immunosuppression3, and carries a poor prognosis. Phototherapy and steroid ointment was initiated with initial benefit and regression of rash but then rash and edema returned within 6 months. Ruxolitinib was given on expanded access protocol with no benefit. Systemic steroids were again initiated at 1 mg/kg/ day with minimal benefit. Insurance denied tociluzumab. Extracorporeal photopheresis was started with only minimal response and eventually ibrutinib was initiated. With steroids, photopheresis and ibrutinib she had marginal response but ongoing severe skin GvHD. She had numerous infectious complications including soft tissue skin infections requiring multiple admissions. At 16 months post transplant, the patient began a medical cannabis product manufactured by VIREO HEALTH, consisting of a high CBD:THC ratio (19:1) oral solution containing CBD 47.5mg/ml and THC 2.5mg/ml. A daily dose of 6 ml provided 285 mg CBD and 15mg THC daily comparable to the 300 mg CBD product in the Kalytera product. Toxicity was sleepiness; thus the patient took the dose in the evening. There was a definite response within 3 months, allowing discontinuation of ibrutinib and photopheresis. By 2 years post transplant, her skin issues had resolved with only mild itching and flakiness. She remains on this product at a dose of 6 ml daily. This case adds to the developing evidence regarding the potential anti- inflammatory and immunosuppressive effects of medical cannabis and its activity for the treatment of active GVHD. Both THC and CBD are anti-inflammatory via CB2 receptors and THC inhibits T-lymphocyte expansion in a murine BMT model.1 The THC component may have contributed therapeutic benefit but also explains the toxicity and was dose limiting. Further studies are warranted to explore the role of medical cannabis, the optimal dose of CBD and THC, in the prevention and management of GVHD. 1 Yeshurun, Moshe, et al. "Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study." Biology of Blood and Marrow Transplantation, vol. 21, no. 10, 2015, pp. 1770-1775., doi:10.1016/j.bbmt.2015.05.018. 2. Kalytera Therapeutics Announces Encouraging Results of a Phase 2a Clinical Study for the Treatment of Acute Graft versus Host Disease. Source: Kalytera Therapeutics, Inc.VANCOUVER, British Columbia, Feb. 22, 2017 (GLOBE NEWSWIRE) 3. Creamer D, Martyn-Simmons CL, Osborne G, et al. Eczematoid Graft-vs-Host Disease: A Novel Form of Chronic Cutaneous Graft-vs-Host Disease and Its Response to Psoralen-UV-A Therapy. Arch Dermatol.2007;143(9):1157-1162. doi:10.1001/archderm.143.9.1157 Figure Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: This is a medical cannabis product manufactured by VIREO HEALTH, consisting of a high CBD:THC ratio (19:1) oral solution containing CBD 47.5mg/ml and THC 2.5mg/ml. The drug was used to treat refractory graft versus host disease.

Introduction: Haplo-cord transplantation - the co-infusion of a single umbilical cord graft with CD34-selected cells from a haplo-identical donor, offers an alternative stem cell source for patients lacking HLA-matched donors. The T-cell depleted haplo-graft acts as a myeloid bridge until replaced by durable cord hematopoiesis. 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. ATG depletes T-lymphocytes through Fas-mediated apoptosis, but also indirectly stimulates T-cell destruction through antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) (de Koning, Blood Adv. 2018). Excessive depletion of cord lymphocytes may compromise immune reconstitution and graft vs. tumor effects. G-CSF administration early post-transplant may sensitize cord lymphocytes to the cytotoxic effects of residual ATG. G-CSF drives myeloid precursor proliferation and activates phagocytosis, facilitating increased ADCP and ADCC of ATG-coated cells (de Koning, Blood Adv, 2018). Prior to the publication of this data, our institutional practice was to administer G-CSF to haplo-cord transplant recipients from day +6 until neutrophil engraftment. In April 2018, we altered our practice - withholding routine G-CSF treatment. We here compare our transplant outcomes 1 year before and after this practice shift. Methods: We examined consecutive adult patients with hematologic malignancy that underwent haplo-cord transplantation conditioned with fludarabine and melphalan with or without total body irradiation (400 cGy) at Weill Cornell Medicine, between 04/2017 and 04/2019. All patients received rabbit ATG (Thymoglobulin) 1.5 mg/kg on days -5, -3 and -1 (total dose 4.5 mg/kg). Data was collected as part of study 01810588 registered at clinicaltrials.gov. Probabilities of relapse, relapse-related mortality (RRM) and non-relapse mortality (NRM) were generated using cumulative incidence (CI) estimates to accommodate competing risks. Probabilities of overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates and inter-group comparison performed by log-rank testing. Variables with potential survival impact were evaluated in a Cox proportional hazards regression model. Results: The study included 59 haplo-cord recipients - 30 who received G-CSF (GCSF group) and 29 who did not (NO GCSF group). Groups were well matched for age, weight, disease, DRI, baseline lymphocyte count, CMV recipient/donor status and TBI treatment (Table). Neutrophil engraftment occurred at a median of 10 days in the GCSF group vs. 14 days in the NO GCSF group (p=0.0002), and platelet recovery at a median of 20 and 22 days (p=-0.61). Primary graft failure occurred in 1 GCSF patient and 2 NO GCSF patients (p=0.53). The incidence of acute GVHD (grade II-IV) by day 100 was 10% in both groups (p=0.97). There was no significant difference between GCSF and NO GCSF in the CIs of relapse, RRM or NRM at 1yr. No difference was found in 1yr OS or PFS on univariate analysis (Table). After adjusting for patient age, weight, lymphocyte count prior to ATG, disease subtype, CIBMTR disease risk index (DRI), Karnofsky performance status (KPS), comorbidity score and TBI exposure, in multivariate analysis, no effect on OS or PFS was observed. CMV reactivation was observed in 40% (GCSF) vs. 21% (NO GCSF) (p=0.11). The trend towards lower reactivations in the NO GCSF may in part be due to the introduction of letermovir prophylaxis for CMV positive transplant recipients in 02/2018. Acknowledging the limited follow up of NO GCSF patients, we note a trend towards improved CD4 counts at 1yr in this group - median 271 cells/μL (n=6, IQR25-75 = 240-342) vs. 155 cells/μL in the GCSF group (n=16, IQR25-75 = 111-473) (p=0.17). Conclusion: Our data shows that G-CSF can safely be eliminated from haplo-cord transplant. We see a delay in neutrophil engraftment but no adverse effect on early morbidity or mortality outcomes. We continue to withhold early G-CSF while assessing long-term outcomes. Longer follow-up is needed in our cohort to enable a systematic analysis of immune reconstitution. Early CD4+ cell recovery after ATG treatment has been shown to improve OS, PFS, NRM and RRM (Admiraal, Lancet Hem 2015 & 2017). Disclosures Van Besien: Miltenyi Biotec: Research Funding.

This phase I study evaluated the maximal tolerated dose of CPX-351 when administered sequentially with allogeneic hematopoietic stem cell transplantation (HSCT) in patients with refractory acute leukemia. CPX-351 is a novel liposomal formulation that combines cytosine arabinoside (ara-c) and daunorubicin in a fixed molar ratio of 5:1. Patients in cohorts of 3 were treated with CPX-351 followed by fludarabine and busulfan (Bu/Flu) conditioning at 4-week (schedule A) or 3-week (schedule B) intervals. CPX-351 doses were escalated in 20-U/m2 increments starting at 60 U/m2 for 3 doses. Of the 36 patients enrolled, 29 were able to undergo HSCT, and the other 7 (the majority on schedule A) did not proceed to HSCT because of rapid disease progression. The maximal tolerated dose of CPX-351 was not reached at the 120 U/m2 × 3 dose level. All 29 patients who proceeded to HSCT demonstrated adequate neutrophil and platelet engraftment. The median follow-up on the study for all 36 patients was 205 days (range, 20 to 996 days). The 1-year cumulative incidence of relapse for the 36 patients was 60.1% (95% confidence interval [CI], 43.4% to 77.3%), and that of nonrelapse mortality was 23.8% (95% CI, 10.9% to 47.4%). The 1-year overall survival and leukemia-free survival were 37% (95% CI, 21% to 53%) and 27% (95% CI, 13% to 43%), respectively. Our data suggest that a phase II trial should incorporate CPX-351 120 U/m2 × 3 dosing on schedule B. Patients with good performance status and those who achieve effective cytoreduction from CPX-351 derived the greatest benefit.

Bendamustine has efficacy in multiple myeloma with a toxicity profile limited to myelosuppression. We hypothesized that adding bendamustine to autologous stem cell transplant conditioning in myeloma would enhance response without significant additional toxicity. We conducted a phase 1 trial adding escalating doses of bendamustine to the current standard conditioning of melphalan 200 mg/m2. Twenty-five subjects were enrolled into 6 cohorts. A maximum tolerated dose was not encountered and the highest dose level cohort of bendamustine 225 mg/m2 + melphalan 200 mg/m2 was expanded to further evaluate safety. Overall, there was no transplant related mortality and only one grade 4 dose-limiting toxicity was observed. Median number of days to neutrophil and platelet engraftment were 11 (range, 9 to 14) and 13 (range, 10 to 21), respectively. Disease responses at day +100 posttransplantation were progression in 5 (21%), partial response in 1 (4%), very good partial response in 7 (33%), complete response in 1 (4%), and stringent complete response in 9 (38%). Six patients (24%) with pre-existing high-risk disease died from progressive myeloma during study follow-up, all at or beyond 100 days after autologous stem cell transplant. Bendamustine up to a dose of 225 mg/m2 added to autologous stem cell transplantation conditioning with high-dose melphalan in patients with multiple myeloma did not exacerbate expected toxicities.

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.

Background aims An accurate and reliable assessment of bone marrow engraftment (BME) after hematopoietic stem cell transplantation (HSCT) is based on the ability to distinguish between recipient and donor cells at selected polymorphic short tandem repeat (STR) DNA loci. Buccal cells are an important source of DNA for determining the recipient's constitutional genotype, particularly in patients transplanted before the STR evaluation. Methods Genomic DNA was extracted from the recipient buccal cells and from isolated CD3+ (T-cell lymphocyte) and CD33+ (myelocyte) cells after HSCT. BME analysis was performed using a STR-based polymerase chain reaction amplification method followed by fragment-size analysis for assessing the recipient-derived or donor-derived composition of cell lineage-specific peripheral blood DNA. Results We identified three cases of complete buccal epithelial cell engraftment after HSCT detected by BME analysis, potentially leading to misinterpretation of testing results if these cells were used as the sole source for determining the recipient's genotype. Conclusions These cases suggest that complete engraftment of buccal epithelial cells may be a common finding in patients receiving HSCT, drawing attention to important issues such as the type of samples used for determining a patient's constitutional genotype that may confound testing results. This study also highlights the need for careful interpretation of the BME testing results in the context of the clinical findings.

Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial.

Hepatic veno-occlusive disease, or sinusoidal obstruction syndrome (VOD/SOS), is a serious and potentially fatal complication of conditioning for hematopoietic stem cell transplantation (HSCT) or of chemotherapy regimens alone. Defibrotide is a complex mixture of single-stranded polydeoxyribonucleotides that is approved in the United States for treating hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT and in the European Union, Israel, and South Korea for treating severe hepatic VOD/SOS post-HSCT. Defibrotide was previously available in the United States as an investigational drug through a treatment protocol (treatment IND) study. Interim results of that large, treatment IND study of patients with VOD/SOS and with or without multiorgan dysfunction (MOD; also known as multiorgan failure) are presented here. Defibrotide was administered i.v. at 6.25 mg/kg every 6 hours (25 mg/kg/day), with a recommended treatment duration of at least 21 days. Enrolled patients (n = 681) were diagnosed with VOD/SOS based on Baltimore or modified Seattle criteria or liver biopsy analysis. Among the 573 HSCT recipients, 288 (50.3%; 95% confidence interval [CI], 46.2% to 54.4%) were alive at day +100 post-HSCT. Day +100 survival for the pediatric (≤16 years) and adult (>16 years) subgroups was 54.5% (95% CI, 49.1% to 60.0%; n = 174 of 319) and 44.9% (95% CI, 38.8% to 51.0%; n = 114 of 254), respectively. In the MOD subgroup, 159 of 351 patients (45.3%; 95% CI, 40.1% to 50.5%) of patients were alive at day +100 post-HSCT. Treatment with defibrotide was generally well tolerated, and drug-related toxicities were consistent with previous studies. Adverse events were reported in 69.6% of safety-evaluable patients (399 of 573). Other than VOD/SOS and associated MOD symptoms, the most commonly reported treatment-emergent adverse event was hypotension (13.8%). Day +100 survival results observed in this trial were consistent with results seen in previous trials of defibrotide for VOD/SOS in adult and pediatric patients. These data support the potential benefit of defibrotide in treating a VOD/SOS patient population that includes those with and without MOD.

Advanced systemic mastocytosis (advanced SM), a rare disease closely associated with KIT mutations (most commonly KIT D816V), encompasses three variants: systemic mastocytosis (SM) with an associated hematologic clonal non-mast cell disorder, aggressive SM, and mast cell leukemia. All variants are associated with shortened survival. Although interferon-alpha or cladribine exhibit efficacy in selected patients, they do not result in cure. Imatinib is approved for the minority of aggressive SM patients with negative or unknown KIT D816V status. The multikinase/KIT inhibitor midostaurin is a promising agent for patients with advanced SM and is currently available on an investigational basis. We recently reported the largest retrospective study of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with advanced SM (n=57). The evidence from this study and a few case reports indicate that it can cure some patients and lead to long-term survival. However, there is still a significant gap of knowledge regarding the use of this high-intensity therapy in advanced SM. The present paper provides a consensus opinion on methods to optimize decision-making regarding the use of alloHCT in this patient population in light of currently available data. In addition, we outline strategies that combine midostaurin in the peritransplant setting. Such protocols should generate useful outcome data regarding the safety and efficacy of KIT inhibition in conjunction with high-intensity therapy in the treatment of advanced SM.

Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood (UCB) graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic graft-versus-host disease (GVHD). But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very-high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% versus 11% p

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

This prospective, randomized, double-blind, placebo-controlled study evaluated the efficacy of palifermin to reduce the incidence of severe (grade 3-4) acute GVHD after myeloablation and allo-SCT. Adults who received allo-SCT for hematologic malignancies received placebo or palifermin 60 μg/kg daily on three consecutive days before conditioning and a single dose of 180 μg/kg after conditioning, but often 1 or 2 days before allo-SCT. Subjects received MTX (plus CYA or tacrolimus) on days 1, 3, 6 and 11. Acute GVHD was evaluated once weekly and oral mucositis was evaluated daily. Subjects were randomly assigned to placebo (n=78) or palifermin (n=77). Conditioning included TBI in approximately half of the subjects (48% placebo, 51% palifermin). The primary efficacy end point, subject incidence of grade 3-4 acute GVHD, was similar between treatment groups (17% placebo, 16% palifermin). Grade 3-4 oral mucositis (73% placebo, 81% palifermin) and other secondary efficacy end points were similar between treatment groups. The most commonly reported treatment-related adverse events were skin/s.c. events such as rash, pruritus, and erythema. This exploratory study of acute GVHD after myeloablation and allo-SCT did not provide evidence of a treatment effect with this dosing regimen of palifermin.

The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).

Introduction: Mutations at diagnosis in acute myeloid leukemia (AML) patients have prognostic implications. For AML patients undergoing allogeneic stem cell transplant (SCT), the prognostic impact of molecular mutations pre-transplant and immediately post-transplant are less well characterized. Here we examine the mutation status of AML patients at different time points in relation to allogeneic SCT and their implications in relapse and survival. Methods: AML patients who underwent allogeneic SCT after achieving complete remission with available molecular mutation testing at diagnosis, prior to transplant (within 4 weeks), and 28 days post-transplant were included in the analysis. Multivariable cox regression analysis was adjusted for age, gender, CIBMTR disease risk index (DRI), type of transplant, and genetic mutation. Backward selection method was used to select the best combination of genes that is associated with OS and relapse-free survival (RFS). Results: A total of 110 AML patients with molecular genetic data available from 2014 to2018 at Weill Cornell Medicine were included in the analysis. Clinical characteristics of the patients are summarized in Table 1. The median age was 58 years (20-77). Twenty-three molecular mutations analyzed at baseline, pre-transplant, and at 28 days are listed in Table 2. With a median follow-up time of 31.6 month, the median overall survival for the cohort was 37.1 months. Eighty-one patients had molecular testing at diagnosis. 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 RFS, but not OS on multivariate analysis. Seventy-seven patients had molecular testing prior to transplant and 27 patients had persistent mutations (Table 2). The presence of mutations in ETV6 and FLT3-ITD were independently associated with worse RFS ((HR 49.7, p=0.001, CI 5.0-528) & (HR 36.4, p At 28 days post-transplant, only 9 of the 84 patients had persistent mutations. Persistence of FLT3-ITD conferred worse RFS and OS in both univariate ((HR 11.92, p=0.0218, CI 1.43-98.98) & (HR 25.16, p=0.0052, CI 2.62, 241.92)) and multivariate ((HR 18.13, p=0.0089, CI 2.07-158.86) & (HR 35.47, p=0.0028, CI 3.41-368.81)) analysis. Conclusions: Persistent presence of mutations in ETV6 and FLT3-ITD prior to stem cell transplant were associated with shorter RFS and OS independent of CIBMTR DRI. Persistent mutations in NRAS and CBL prior to stem cell transplant were associated with poor RFS and OS respectively. This analysis further supports association of adverse outcomes in AML patients with selected persistent mutations prior to stem cell transplant. Utility of serial mutation testing prior to transplant should be further investigated in prospective studies. Disclosures Lee: AstraZeneca: Consultancy; Clinipace: Consultancy; Karyopharm Therapeutics Inc: Consultancy; LAM Therapeutics: Research Funding; Amgen: Consultancy. Ritchie:NS Pharma: Research Funding; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau; Astellas Pharma: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau. Desai:Argenx: Consultancy; Cellerant Inc: Consultancy. Roboz:Eisai: Consultancy; Pfizer: Consultancy; AbbVie: Consultancy; Roche/Genentech: Consultancy; Aphivena Therapeutics: Consultancy; Eisai: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Argenx: Consultancy; Novartis: Consultancy; Janssen Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Orsenix: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Cellectis: Research Funding; Celltrion: Consultancy; Celgene Corporation: Consultancy; Celltrion: Consultancy; Argenx: Consultancy; Astex Pharmaceuticals: Consultancy; Bayer: Consultancy; Cellectis: Research Funding; Sandoz: Consultancy; Astex Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy; Sandoz: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Roche/Genentech: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Aphivena Therapeutics: Consultancy; Pfizer: Consultancy.

Background: Allogeneic stem cell transplant remains the only curative modality for myelodysplastic syndrome (MDS), yet there is significant controversy and individual practice variation in offering pre-transplant therapy with the goal of reducing disease burden and/or improving marrow function. In this study, we analyze the impact of bone marrow response prior to transplant on the post-transplant overall survival and relapse. Methods: We collected data from 2007 to 2018 from patients undergoing allogeneic transplant for MDS at Weill Cornell Medicine. Patients with MDS transformed to AML were excluded. P values for survival analyses were derived from Cox models. All statistical tests were 2 sided with 0.05 alpha levels. Results: We analyzed 85 patients who underwent an allogeneic stem cell transplant for MDS and had all pertinent data available. Response to pre-transplant treatment was not a pre-requisite for proceeding to transplant. The donor source was MUD, MRD and cord blood in 40%, 37.65%, and 22.35% of patients, respectively. Median age at the time of transplant was 61 years (32.94% females). IPSS-R at diagnosis was low, intermediate, high and very high-risk in 12.94 %, 31.76 %, 24.71% and 30.59% of patients, respectively. Most (80%) patients were treated with hypomethylating agents (HMA) prior to transplant. Within 2 months of transplant, 27.06% of patients achieved CR, with 8% cytogenetic response. Hematological improvement (HI) only (without marrow CR), marrow CR and stable disease/no response were seen in 9.41%, 18.83% and 42.35% of patients, respectively. Bone marrow blasts were 0-5%, 5-10% and 11-19% in 77.5%, 18.75% and 3.75% of patients pre-transplant, respectively. Median overall survival after transplant was 28.6 months (range 14.9-48.5). 90-day transplant related mortality was 10.7 %. One-year survival after transplant was 65.7%; with a relapse rate of 30.6% at median follow up of 12 months. The incidence of grade 3 and 4 GVH of any kind was 33.33%. Using univariate models, age at transplant (HR 1.049, 95% C.I. 1.017-1.083, p value 0.002) and a high IPSS-R (p value.004) at diagnosis were associated with inferior post-transplant survival, while gender and use of HMA prior to transplant did not impact post-transplant survival. In multivariate cox regression analyses adjusting for other confounding variables, achieving a CR or HI was significantly associated with higher post-transplant survival, compared to stable disease/no response prior to transplant (HR 0.46, 95% C.I. 0.23-0.90, p value 0.02). Achievement of a marrow CR resulted in a trend toward higher post-transplant OS (HR 0.45, 95% C.I. 0.18-1.09, p value 0.07). Pre- transplant blast percentage (10%) or cytogenetic response only (without CR) did not impact survival outside the presence of a CR. In the multivariate models IPSS-R very high risk at baseline (HR 4.75, 95% C.I. 1.81-12.43, p value 0.001) was associated with reduced post-transplant OS compared to low risk. There was no association between the types of marrow response on RFS post-transplant. Of note, among 34 patients with baseline mutations in ASXL1, ETV6, EZH2, RUNX1 and TP53, mutation clearance at the time of transplant was observed in only 6/34 (17.6%) patients. The presence of a mutation in any of these 5 genes prior to transplant did not impact RFS (HR 1.12, 95% C.I. 0.38-3.26, p value 0.04) or OS (HR 3.09, 95% C.I. 0.86-11.11, p value 0.08). However, we were not able to assess the effect of individual mutations (e.g. TP53) due to small numbers. We did not see an effect of GVHD type (acute or chronic) or grade on RFS or OS. Conclusions: Achievement of CR or hematological improvement (HI) prior to allogeneic transplant was associated with superior survival post-transplant, while marrow CR and cytogenetic response did not impact post-transplant survival any different than going into allogeneic transplant with stable disease/no response. IPSS R score at diagnosis was associated with inferior post-transplant survival. The presence of mutations in ASXL1, ETV6, EZH2, RUNX1 or TP53 genes prior to transplant did not appear to impact OS or RFS post-transplant, but the total numbers were small. Although CR or HI after pre-transplant treatment improved OS post-transplant, only one third of patients achieved these responses prior to transplant. Better MDS directed treatments and conditioning regimens are needed to improve outcomes after allogeneic transplantation. Figure. Figure. Disclosures Desai: Cellerant Inc: Consultancy; Argenx: Consultancy. Lee:LAM Therapeutics: Research Funding; AstraZeneca: Consultancy; Karyopharm Therapeutics Inc: Consultancy; Amgen: Consultancy; Clinipace: Consultancy. Ritchie:Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; NS Pharma: Research Funding; ARIAD Pharmaceuticals: Speakers Bureau; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau. Roboz:Orsenix: Consultancy; AbbVie: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Celltrion: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Argenx: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Cellectis: Research Funding; Janssen Pharmaceuticals: Consultancy; AbbVie: Consultancy; Eisai: Consultancy; Novartis: Consultancy; Bayer: Consultancy; Astex Pharmaceuticals: Consultancy; Aphivena Therapeutics: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; Orsenix: Consultancy; Jazz Pharmaceuticals: Consultancy.

Introduction: Umbilical cord blood (UCB) transplant supported by third party CD34-selected cells results in rapid count recovery, UCB mediated GVL effects and low rates of chronic GvHD. For patients lacking haplo-identical relatives, other sources of CD34 progenitors are needed. Methods: We identified partially matched unrelated donors for patients lacking suitable haplo-identical donors -including second-degree relatives - and who otherwise were candidates for haplo-cord transplant. Most were treated on prospective studies (clinicaltrials.gov 00943800 and 01810588). For 5 patients, UCB were obtained through NCT01351545. Results: Between 12/2014 to 7/2018 of 126 candidates for haplo-cord transplant, 26 (21%) had no suitable related donor. Most common reasons were: no first or second degree partially matched donors, ill or unavailable relative, high titers of HLA-antibodies against all relatives, or evidence of hematological familial hereditary syndrome. Diagnoses were: 16 AML/MDS, 5 ALL, 2 MPN, 1 NHL, 1 plasma cell leukemia and 1 SAA. Median age was 57 (24-75). 50% were women. 42% non-Hispanic white (NHW), 19% non-Hispanic blacks (NHB), 19% Hispanic, 8% other minorities. CIBMTR Disease Risk Index (DRI): 46% intermediate, 38% high and 8% very high. Median HCT-CI was 3.5 (25%-75% IQR 2-6). Conditioning: 16 Flu/Mel/TBI (94% 400cGray), 8 Flu/Mel,1 Flu/Cy, 1 Etoposide/TBI. All except 1 received ATG 4.5 mg/kg and all received post-transplant Tacrolimus and MMF. UCB matching was 4/8, 5/8, 6/8 or 7/8 HLA in 12%, 27%, 23%, and 38%, respectively. HLA matching for unrelated haplos was 5-6/12, 7-8/12, >9/ 12 HLA in 15%, 54% and 19%, respectively. For UCB, median cells collected were 2.1 (range1.1-4.0) ×107 TNC/kg. CD34 cell dose of unrelated donor graft was 3-5 ×106 CD34/kg. Median time to ANC engraftment was 11 days (range 9-35) and platelet engraftment was 18 days (range11-124). Chimerism on day 56 are shown in figure 1. There were three patients with graft failures: Pt #5 with complete graft rejection, autologous reconstitution, but ongoing clinical remission that persists to date (Day+ 1223); Pt #13 with graft failure and subsequent relapse, rescued with second UCB HSCT but died of progression of disease; and pt #18 who died from infectious complications after graft failure. Acute GvHD occurred in 35% of patients (4 Grade I-II, 4 Grade III, and 1 Grade IV). cGvHD was rare: One patient with mild severity and a second with severe lung involvement. After a median follow up of 209 days, 6 months cumulative incidence of relapse (CIR) was 16% and non-relapse mortality (NRM) was 20%. Median OS was 14 months (95%CI 7-27). Conclusion: 20% of adults without matched related or unrelated donors, also lack suitable first or second degree haplo-identical donors. UCB transplant with partially matched unrelated donor accessory cells provides an alternative for transplantation. Engraftment is rapid, rates of acute GVHD are acceptable and incidence of chronic GVHD is very low. Prolonged survival is encouraging in this patient cohort with adverse characteristics and who would not be candidate for haplo-identical HSCT. Disclosures No relevant conflicts of interest to declare.

Background Conventional salvage chemotherapy has limited efficacy in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). In the last decade, several novel agents, including pralatrexate, an antifolate, brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate, and romidepsin, a histone deacetylase inhibitor, have been introduced into clinical practice based on phase 2 data demonstrating efficacy in relapsed/refractory (R/R) diseases. Their impact on real world survival remains to be defined. In this single-center retrospective cohort study we assessed survival including outcomes after hematopoietic stem cell transplant (HSCT) with respect to novel agent exposure. Methods Patients diagnosed with PTCL from 2012-2017 who consented for inclusion in the Weill Cornell lymphoma and bone marrow transplant databases with adequate treatment records were included. Medical records were reviewed for baseline characteristics, treatment course, and outcomes including overall survival and HSCT. Median follow-up time was estimated on overall survival by reverse Kaplan-Meier method. Overall Survival (OS) time was calculated from date of diagnosis to date of death or last follow-up. Kaplan-Meier estimator was used to estimate survival probability. Survival difference between groups was tested by log-rank test and Cox regression analysis for statistical significance. Results A total of 123 cases were reviewed with median follow-up of 34 months. The major PTCL subtypes were PTCL NOS (N=34, 27.6%), angioimmunoblastic T-cell lymphoma (N=21, 17%), adult T-cell leukemia/lymphoma (N=19, 15.4%), and anaplastic large cell lymphoma (N=14, 11.4%). The most common 1st line chemotherapy regimens were CHOP (N=34, 31.5%), EPOCH (N=21, 19.4%), or CHOEP (N=10, 9.3%). Ninety-two patients had relapsed or refractory disease, and the most common 2nd line therapies were DICE/ICE (N=17, 18.4%), gemcitabine-based regimens (N=6, 7.5%), bendamustine (N=5, 5.4%), hyperCVAD (N=5, 5.4%), or combinations of novel agents. Thirty-three R/R patients received a novel agent, including pralatrexate alone (N=3), BV (N=13), or romidepsin (N=17). Thirty-six R/R patients underwent HSCT, including 26 allogeneic and 10 autologous. Baseline characteristics at diagnosis including age, gender, Ann Arbor stage, ECOG status, and IPI were similar between R/R patients who received a novel agent and those who did not. Although no differences in OS were seen with novel agent use among patients with R/R disease, there was a significant difference in OS among patients who received HSCT and those who did not (p=0.012 by log-rank test). Compared to no HSCT, significantly improved survival was observed in patients receiving allogeneic HSCT (HR = 0.47, p = 0.03) as well as autologous HSCT (HR = 0.27, p= 0.03) by Cox regression survival analysis, both univariate and multivariate when adjusting for interaction with novel agents. Conclusion Data from this single-center retrospective cohort study suggest that hematopoietic stem cell transplant, both autologous and allogeneic, was associated with overall survival benefit in R/R diseases in the novel agent era. The real world impact of novel agents use in PTCL subtypes warrants further study, preferably in a prospectively designed multicenter population study with larger sample size where disease subtypes, therapeutic targets of novel agents, and line of therapies can be sufficiently delineated for response and survival analysis. Disclosures Martin: AstraZeneca: Consultancy; Gilead: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Kite: Consultancy. Allan:Acerta: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Furman:TG Therapeutics: Consultancy; Sunesis: Consultancy; Loxo Oncology: Consultancy; Incyte: Consultancy, Other: DSMB; Gilead: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Verastem: Consultancy; Janssen: Consultancy; AbbVie: Consultancy.

Background: Although current antiretroviral therapies have effectively changed the course of HIV-1 infection, it remains an incurable illness. The C-C chemokine receptor type 5 (CCR5) is the key co-receptor for HIV entry into CD4+ T cells. Homozygous 32 deletion (delta32) in CCR5 genes leads to resistance to HIV-1 infection 1. Allogeneic stem cell transplant from a donor with CCR5 delta32/32 mutation was curative for HIV in an HIV-1-infected man (Berlin Patient) with AML 2. It has been challenging to replicate this experience. We present our experience with a single case of successful engraftment of CD34-selected, related haploidentical peripheral blood and CCR5delta32 cord blood stem cell transplant (haplo-cord) in an HIV-1-infected woman who, like the Berlin patient, developed AML and is now doing well at almost one-year post transplantation. Clinical case: A 60-year-old African-American woman was diagnosed with HIV-1- infection in June 2013 and was started on an antiretroviral treatment (ART) regimen consisting of tenofovir, emtricitabine and raltegravir. Her pre-ART viral load and CD4 counts were 1,000,000 copies/ml and 1003 cells/mm3, respectively. In Nov, 2013 she had viral load < 20 copies/ml with CD4 counts of 980 cells/mm3 and her HIV-1 infection was relatively asymptomatic. In March 2017, she was diagnosed with AML with monosomy 7. Her HIV therapy after the AML diagnosis was changed to abacavir- lamivudine -dolutegravir- combination. She achieved morphologic and cytogenetic remission after 1 cycle of standard idarubicin/cytarabine induction chemotherapy. In addition, she received 1 cycle of HiDAC consolidation and was referred for allogeneic stem cell transplant. We identified a CCR5 delta32/32 mutated cord blood unit (CBU) which was 5/8 HLA matched and contained 1.3 x 107 nucleated cells/kg and 3.2 x 104 CD34+ cells/kg. She underwent a combined CD34-selected, haploidentical peripheral blood and CCR5delta32 cord blood stem cell transplant (haplo-cord) in August 2017. Her conditioning regimen was with fludarabine/melphalan/and TBI400 and she also received ATG/MMF/tacrolimus for GVHD prophylaxis. Her neutrophils and platelets engrafted on day 10 and 16, respectively and she was discharged on day +16 post-transplant. Her post-discharge hospital course was complicated by CMV reactivation (no organ involvement) 2 months post-transplant with peak viral level of 1374 copies/ml. She did not have evidence for EBV re-activation or graft-vs-host disease. Her plasma HIV viral load remained undetectable post- transplant while remaining on abacavir/lamivudine and dolutegravir-based ART. Her day+180 bone marrow showed continued AML remission and she remains in clinical remission near one year post-transplant. CD3 chimerism showed 82% haploidentical donor and 8% CBU and 10% recipient on day +15 post-transplant (Figure 1). The chimerism composition switched to 96% CBU by day+34, and became and remained 100% CBU since day+55. CD33 chimerism showed 98% haploidentical donor and 2% cord donor on day+15 post-transplant. It was 81% haploidentical donor and 19% cord on day+55 and became 100% cord by day+100. She has continued CD4, CD8, NK and CD19 cell recovery, with normal T cell subsets currently (Figure 2). Her CD4 count dropped to 27 cells/mm3 at one-month post-transplant and currently is at 673cells/mm3. She is currently 11 months post-transplant and is back to her normal daily activities Conclusion: Haplo-cord transplantation with CCR5 delta 32/32 CBU resulted in rapid engraftment and immune replacement with dominance of the CCR5 delta 32/32 CBU graft in an HIV-1-infected woman. Successful suppression of HIV-1-replication to clinically undetectable levels was maintained throughout the transplant period for up to one year. . Correlative viral and immunological studies are ongoing, along with effects on the latent reservoir, which was detectable pre-transplant. It is possible to identify appropriate CCR5 delta 32/32 CBU units for haplo-cord transplantation in HIV-1- infected patients with implications for HIV-1 cure. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Background Fluoroquinolone (FQ) prophylaxis is widely used to prevent bloodstream infections (BSIs) in neutropenic patients undergoing hematopoietic stem cell transplantation (HCT). In order to assess whether increasing FQ resistance threatens the effectiveness of FQ prophylaxis, we screened HCT recipients for colonization with FQ-resistant Enterobacteriaceae (FQRE) and assessed the impact of colonization on the risk of BSI. Methods We collected stool samples on admission for HCT and weekly until neutrophil engraftment from patients at NewYork-Presbyterian Hospital/Weill Cornell Medical Center from November 2016 to March 2018. Patients received FQ prophylaxis during neutropenia. Perianal swabs were used when stool was unavailable. Stool and swab samples were plated onto MacConkey agar with 1 μg/mL ciprofloxacin, and colonies were identified and underwent antimicrobial susceptibility testing. We determined the prevalence of colonization with FQRE on admission for HCT, the risk of acquiring FQRE, and compared the risk of BSI during the transplant admission in colonized and noncolonized patients. Results We evaluated 178 HCT recipients and found that 35 (20%) had pre-transplant FQRE colonization (allogeneic: 20/89, 22%; autologous: 15/89, 17%). Thirty FQRE (86%) were Escherichia coli, 5 (14%) were Klebsiella pneumoniae, and 13 (37%) were extended-spectrum β-lactamase producers. Five (14%) of the 35 patients with pre-transplant FQRE colonization developed BSI due to an Enterobacteriaceae, and all bloodstream isolates had identical susceptibility profiles to the colonizing FQRE. In contrast, only one (1%) of 143 patients without pre-transplant FQRE colonization developed Enterobacteriaceae BSI (P = 0.001). Patients with pre-transplant FQRE colonization also had higher rates of any Gram-negative BSI (20% vs. 1%, P < 0.001), but did not have increased risk of Gram-positive BSI (6% vs. 11%, P = 0.5). Of 123 patients without initial FQRE colonization who had follow-up samples collected, 10 (8%) acquired FQRE during post-HCT neutropenia. Conclusion FQRE colonization is common on admission for HCT and is associated with decreased effectiveness of levofloxacin prophylaxis in preventing Gram-negative BSI during post-transplant neutropenia. Disclosures M. J. Satlin, Hardy Diagnostics: Grant Investigator, Research support; Allergan: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient; Biomerieux: Grant Investigator, Grant recipient; Achaogen: Consultant, Consulting fee. R. Malherbe, Hardy Diagnostics: Employee, Salary. S. G. Jenkins, Merck: Grant Investigator, Grant recipient. L. F. Westblade, Accelerate Diagnostics: Grant Investigator, Grant recipient; Biomerieux: Grant Investigator, Grant recipient; Allergan: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee.

Background Seasonal influenza causes significant morbidity and mortality on HSCT recipient. The 2017–2018 influenza has been characterized in the United States by prolonged high rates of both influenza A (IAV) and B (IBV) and low vaccine effectiveness. The aim of this study was to assess the impact of both IAV and IBV during 2017–2018 influenza season on a cohort of stem cell transplant (SCT) recipients at Weill Cornell- NYP. Methods We reviewed charts of HSCT recipients that were diagnosed with influenza by PCR on nasopharyngeal swabs. Demographics, clinical and microbiological data, and outcomes were collected. The study was approved by Weill Cornell Institutional review board. Results From September 2017 to March 2018, 30 stem cell transplant recipient at NYP were diagnosed with influenza. IAV cases peaked in January (11 cases) while IBV infected-patients were equally distributed from December to March. Infected subject were more likely to be male (n = 20, 66.6%) with mean age of 57 ± 12 (IAV) vs. 59 + 11 (IBV). Nine patients had received auto SCT and 21 patient allo SCT. Most commons symptoms were cough (present in all patients), fever (28/30), nausea, dyspnea. Patient received oseltamivir (for 5 or 10 days) in 28/30 cases, with one patient developing resistance under treatment. Interestingly both IAV and IBV caused lower respiratory tract infection (LRTI, 7 cases) with severe pneumonia (IAV 1 cases, IBV 2 cases) and intubation. In two severe cases IV was detected in the BAL. 13 subjects (56%) with a URTI and 4 (43%) subjects with LRTI had not received the influenza vaccine for the season. Prolonged shedding of influenza on oseltamivir treatment was documented in 7 patients. Conclusion Both IAV and IBV are serious threat in SCT population. Vaccination and oseltamivir are useful tools. Resistance testing should be considered in subjects with prolonged disease. Disclosures S. G. Jenkins, Merck: Grant Investigator, Grant recipient. M. J. Satlin, Hardy Diagnostics: Grant Investigator, Research support. Allergan: Grant Investigator, Grant recipient. Merck: Grant Investigator, Grant recipient. Biomerieux: Grant Investigator, Grant recipient. Achaogen: Consultant, Consulting fee. L. F. Westblade, Accelerate Diagnostics: Grant Investigator, Grant recipient. Biomerieux: Grant Investigator, Grant recipient. Allergan: Grant Investigator, Grant recipient. Merck: Grant Investigator, Grant recipient.

Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cells that can be harvested for transduction or gene editing. We therefore performed a phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and ten were on hydroxyurea. Of eight patients who achieved a CD34+ cell concentration >30 cells/μL, six were on hydroxyurea. There was no clear dose response to increasing plerixafor dosage. There was a low rate of serious adverse events; two patients developed vaso-occlusive crises, at the doses of 80 μg/kg and 240 μg/kg. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34 counts, which correlated strongly with peak peripheral blood CD34 counts. Plerixafor administration did not induce significant increases in the fraction of activated neutrophils, monocytes, or platelets. However, increased neutrophils positive for activated β2 integrin and Mac-1 were associated with serious adverse events. In summary, plerixafor was well tolerated but did not achieve consistent CD34+ cell mobilization in this cohort of patients, most of whom were being actively treated with hydroxyurea and only one was chronically transfused. The study will continue with escalation of the dose of plerixafor and modification of hydroxyurea administration. Clinicaltrials.gov identifier: NCT02193191.

Reported median overall survival (OS) in patients with mantle cell lymphoma (MCL) has been reported to be just 3-4 years. As a consequence, first-line treatment has become more aggressive. Single-center studies with R-Hyper-CVAD and/or autologous stem-cell transplant (ASCT) have produced 3-year OS rates80%, prompting many to adopt their use. We evaluated outcomes from a single-center cohort managed in a more traditional fashion.We identified patients with MCL evaluated at Weill Cornell Medical Center since 1997, and included those with known date of diagnosis. An online social security database was used to verify survival.We identified 181 patients with MCL, and date of diagnosis could be determined in 111. Three-year OS from diagnosis was 86% [95% confidence interval (CI) 78% to 92%]. Median OS was 7.1 years (95% CI 63-98 months). Adequate information on therapy was available for 75 patients. Only five were treated upfront with (R)-Hyper-CVAD or ASCT while an additional four patients received one of these regimens subsequently. Treatment type had no significant effect on OS.Outcomes with standard approaches can yield similar survival to that achieved with more intensive approaches. Biases may account for the perceived superiority of aggressive strategies.

This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34+ selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as

Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or a single-arm clinical trial. Of the 16 patients (clinical trial: 9; compassionate use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n = 7), 4 (n = 5), 1 (n = 3), and type 3 and 4 coinfection (n = 1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia, and 8 had a fever. Patients received 5 to 10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and 4 (25%) had a partial response. The 3 patients without a clinical response had coinfections with other pathogens. Of the 7 patients with virologic and spirometric data, 5 had >1-log reduction in nasopharyngeal swab PIV viral load and 4 had improved forced expiratory volumes by the end of treatment. Three patients (19%) died within 30 days and 2 of these deaths were related to PIV infection. Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized placebo-controlled trials are needed to better evaluate its efficacy.

Radioimmunotherapy (RIT) with tositumomab and iodine 131 tositumomab can produce durable and complete responses in relapsed/refractory low-grade Non-Hodgkin's lymphoma. Patients with bone marrow involvement (BMI) with tumor25% of the intertrabecular space are generally excluded from RIT because of risk of excessive hematologic toxicity. The authors conducted a dose-escalation study of tositumomab and iodine 131 tositumomab to determine whether RIT is feasible in this population. Patients had baseline BMI of25% and platelet count ofor=150,000/mm3. In contrast to the usual 75 cGy total body dose of radiation, dose escalation of Iodine I 131 tositumomab began at a total body dose of 45 cGy, and increased to 55 cGy in a second cohort. Dose-limiting toxicity (DLT) was defined as absolute neutrophil count500 cells/mm3 or platelets25,000/mm3 for17 days, or absolute neutrophil count750/mm3 or platelets50,000/mm3 for24 days. Eleven subjects were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI ranged from 30 to 65% (median approximately 40%). Patients had received a median of three prior chemotherapies (range 1 - 6). One of the six evaluable patients treated at 45 cGy experienced DLT. Three patients received 55 cGy, one had hematologic DLT concurrent with lymphoma progression and extensive BMI at relapse. Three of 11 (27%) patients received hematologic supportive care. Two patients had objective responses of 1 and 42.4+ months, respectively. RIT with attenuated dose iodine 131 tositumomab for patients with25% BMI has acceptable toxicity and can result in lymphoma responses.

Thirty consecutive patients underwent hematopoietic stem cell transplantation for myelofibrosis (MF) at our institution. The median age at the time of transplant was 49 (range, 18-68) years, 74% of patients had advanced Dynamic International Prognostic Scoring System (DIPSS) scores, and 83% received reduced-intensity conditioning.With a long follow-up of our patients, we analyzed disease and transplant variables that contributed to engraftment and outcomes.Neutrophil engraftment was achieved in 27 patients (90%) at a median time of 15 (range, 10-44) days, and 19 patients (63%) achieved platelet recovery at a median time of 18 (range, 8-100) days. Splenomegaly was associated with poor neutrophil engraftment (subdistributional hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.21-0.83; P = .01) and platelet engraftment (SHR, 0.18; 95% CI, 0.07-0.48; P .001). Increased levels of lactate dehydrogenase (LDH) was associated with poor platelet engraftment (SHR, 0.39; 95% CI, 0.16-0.94; P = .04). The median follow-up for surviving patients was 49 (range, 3-155) months. The 1-year cumulative incidence of nonrelapse mortality (NRM) and relapse were respectively, 57% (95% CI, 29%-76%) and 25% (95% CI, 7%-48%). Increased levels of LDH was associated with high NRM (SHR, 2.82; 95% CI, 1.08-7.35; P = .03). The 4-year overall survival (OS) and relapse-free survival (RFS) were 44% (95% CI, 29%-67%) and 37% (95% CI, 23%-61%), respectively. In the multivariable model, splenomegaly and Eastern Cooperative Oncology Group (ECOG) performance status (PS)1 were associated with worse OS (hazard ratio [HR], 5.40; 95% CI, 1.19-24.56); P = .03) and RFS (HR, 3.78; 95% CI, 1.01-14.06; P .05), respectively. ECOG PS1 was also associated with worse RFS (HR, 5.00; 95% CI, 1.31-19.14; P = .02). In this patient group with advanced disease, DIPPS score, Lille score, Janus-Associated Kinase V617F (JAK2 V617F) mutation status, and donor type did not predict transplant outcome.We confirm curative potential, but high NRM of allogeneic transplant for advanced MF.

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P

The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days −7 to −3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival., Highlights • We conducted a retrospective comparison of intravenous versus subcutaneous administration of alemtuzumab for graft-versus-host disease prophylaxis in unrelated donor transplant recipients. • We observed a significant reduction in grade ≥ 2 infusion-related reactions after subcutaneous injections. The incidences of acute and chronic graft-versus-host disease were similar. There was no difference in incidence of viral reactivation or fatal bacterial infections. • There was no difference in 30-day mortality or 1-year overall survival between the 2 arms.

Background Hematopoietic stem cell transplants (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Although the epidemiology of many respiratory viruses has been well characterized in this population, little is known about the epidemiology of human coronavirus (HoCV) infection. Methods We identified HSCT recipients with symptoms of a respiratory tract infection who tested positive for HoCV by nasopharyngeal (NP) swab from January 2013 to December 2016 at our hospital. NP swabs were analyzed by the FilmArray® Respiratory Panel, which detects 17 respiratory viruses, including 4 coronavirus serotypes. We reviewed the demographics, transplant type, comorbidities, smoking status, respiratory symptoms, co-pathogens, and radiographic findings of infected patients. We then assessed the incidence of developing a lower respiratory tract infection (LRTI), defined as new pulmonary infiltrates or detection of HoCV in bronchoalveolar lavage fluid, within 30 days of initial diagnosis. Results We identified 58 HSCT recipients who tested positive for HoCV. The median patient age was 54 years, 29 (50%) were men, and 24 (41%) were current or prior smokers. Fifty (86%) patients had received an allogeneic HSCT and 8 (14%) had received an autologous HSCT. The coronavirus serotypes were: OC43 (n = 19, 33%), NL63 (n = 18, 31%), HKU1 (n = 16, 28%), and 229E (n = 5, 9%). The median time from transplant until detection of HoCV infection was 135 days (IQR=256). Seventeen (29%) patients were lymphopenic at the time of diagnosis and 17 (29%) were receiving corticosteroids. The most common initial symptoms were cough (n = 41, 71%), rhinorrhea (n = 31, 53%), and dyspnea (n = 17, 29%), and 19 (33%) and 16 (28%) patients had fever and hypoxia, respectively. Seventeen patients (29%) developed a LRTI within 30 days of diagnosis and 43% harbored a co-pathogen in the blood or respiratory tract. Three patients (5%) were intubated for respiratory failure and 1 (2%) died within 30 days. Conclusion HoCV infection is common in HSCT recipients and is caused by multiple serotypes. Nearly one-third of patients have fever and hypoxia upon initial diagnosis or progress to LRTI. Further research is needed to identify risk factors for HoCV LRTI in this population. Disclosures All authors: No reported disclosures.

was done in all patients and 5 patients had 1-3 courses of DLI. On follow up of the 43 patients with MC, 24 achieved complete chimerism, 10 had stable mixed chimerism and 9 had rejection (mostly level 3 MC). Two patients developed mild graft versus host disease after DLI. Conclusion: Occurrence of mixed chimerism is common after allogeneic HSCT for thalassaemia after Fludarabine/ Treosulfan/Thiotepa conditioning. Rapid tapering of immunosuppression and judicious use of DLI helps in reducing the risk of secondary graft rejection. Closer monitoring of chimerism after HSCT needs to be done when such conditioning regimens are used. Intermediate-1 6 (20%) Intermediate-2 17 (57%) High 5 (17%) JAK 2 Kinase Positive 11 (37%) Negative 11 (37%) Unknown 8 (24) Spleen Enlarged 18 (60%) Normal 4 (13%) Removed 8 (27%) Albumin 1 Median 3.9 Min 2.6 Max 4.9 LDH 2 Median 487 Min 126 Max 1304 ECOG 0 5 1 17 2 4 Unknown 4

Background: Increased baseline white blood cell count (WBC) has been associated with vaso-occlusive complications in sickle cell disease (SCD), raising concern for the use of mobilizing agents that increase WBC count for hematopoietic progenitor cell (HPC) collection for gene therapy. Indeed, G-CSF, which predominantly increases neutrophil counts, when administered to SCD patients can precipitate life-threatening vaso-occlusion. Such vaso-occlusion, however, does not always correlate with degree of white blood cell count elevation (Fitzhugh C et al, Cytotherapy 2009) and G-CSF is associated with increases in neutrophil activation and adhesion. This raises the question whether WBC might be a surrogate for other proposed contributors to vaso-occlusion, such as activation of white cells, platelets, and coagulation. We examined this issue in the context of a clinical study of HPC mobilization with a single dose of plerixafor alone in clinically stable SCD patients. Materials and Methods: 14 patients (13 SS, 1 SB0, median age 31 with range 21-46) have completed the study so far (6 patients at 80 ug/kg, 3 patients at 160 ug/kg, and 5 patients at 240 ug/kg). 10 patients were on hydroxyurea (HU) at a median dose of 25 mg/kg (range 16-28 mg/kg) with a mean HbF of 17% versus 7% for the non-HU treated patients. Only one patient (non-HU treated) had received recent red cell transfusion (for leg ulcers) and had HbA (54%) present. Whole blood was collected at means of 4 hr pre-dose and 12 hr post-dose for activation marker studies by flow cytometry (cell studies) or ELISA (coagulation studies) as listed in Table 1. Results: Increases in absolute total white cell, neutrophil, monocyte, and lymphocyte concentrations in whole blood with plerixafor treatment were all highly significant (Table 2, p < 0.002), without significant differences between HU- and non-HU treated patients or between dose levels. Twelve of 14 patients, however, did not experience any significant adverse events from plerixafor administration. Absolute neutrophil counts (ANC) were strongly correlated with absolute concentrations (but not percentages) of activated β2 integrin neutrophils (r= 1.0) and activated Mac-1 neutrophils (r= 0.8) but no other activation markers. We observed significant plerixafor-associated increases in activation markers (Figure 1) only for ANC subsets positive for activated β2 integrin (1.7± 0.44 fold, mean ± SD, p=0.002) and activated Mac-1 (1.7 ± 1.2 fold, p=0.05), which the correlations with ANC partly explain. The activated Mac-1 significance, however, disappeared with Bonferroni correction. There were no significant differences in activation markers between dose levels or between HU- and non-HU treated patients. There were moderate correlations between activated β2 integrin or activated Mac-1 and absolute reticulocyte count (r= 0.6 for both) and HbF (r= -0.5 for both) but not between these activation markers and LDH. Two patients had pain crises starting at 48 hr (80 ug/kg dose) and 81 hr (240 ug/kg dose) post-plerixafor administration; their pre and post-dose (12 hr) white counts are shown in Table 3. The fold-increase in activation markers for these 2 patients is summarized in Figure 2 (for each activation marker, color-coded arrows point to the two patients) Conclusion: As with G-CSF, elevation of WBC or their subsets with plerixafor is not necessarily associated with vaso-occlusion, as manifested by pain crises. In our study, however, ANC elevation correlated with absolute concentrations of neutrophils positive for activated β2 integrin and activated Mac-1, which were the only activation markers significantly increased with plerixafor. These activation markers in turn correlated with reticulocyte count and HbF, which influence SCD vaso-occlusive severity. Vaso-occlusion as manifested by pain crises, however, was not consistently associated with the highest fold increases in ANC or activation markers. Therefore it remains unclear which bioassays correlate with vaso-occlusion associated with plerixafor mobilization. Disclosures No relevant conflicts of interest to declare.