Search

Purpose: Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS. Patients and Methods: We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1–risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic. Results: Fifty-two patients were enrolled; mean age was 71 years (range 34–93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8–ongoing), 41 weeks (25–ongoing) for LEN, and 88 weeks (8.3–ongoing) for ELT/LEN. Non-hematologic grade 3–4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT. Conclusions: ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

Supplemental Figure 1. Overall Survival Responders vs Non-Responders Supplemental Figure 2. Overall Survival Among Groups

Purpose:Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS.Patients and Methods:We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1–risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.Results:Fifty-two patients were enrolled; mean age was 71 years (range 34–93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8–ongoing), 41 weeks (25–ongoing) for LEN, and 88 weeks (8.3–ongoing) for ELT/LEN. Non-hematologic grade 3–4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.Conclusions:ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

PURPOSE:Cyberattacks targeting health care organizations are becoming more frequent and affect all aspects of care delivery. Cancer care is particularly susceptible to major disruptions because of the potential of immediate and long-term consequences for patients who often rely on timely diagnostic testing and regular administration of systemic therapy in addition to other local treatment modalities to cure or control their diseases. On October 28, 2020, a cyberattack was launched on the University of Vermont Health Network with wide-ranging consequences for oncology, including loss of access to all network intranet servers, e-mail communications, and the electronic medical record (EMR).METHODS:This review details the immediate challenges faced by hematology and oncology during the cyberattack. The impact and response on inpatient, outpatient, and special patient populations are described. Steps that other academic- and community-based oncology practices can take to lessen the brunt of such an assault are suggested.RESULTS:The two areas of immediate impact after the cyberattack were communications and lack of EMR access. The oncology-specific impact included loss of the individualized EMR chemotherapy plan templates and electronic safeguards built into multistep treatment preparation and delivery. With loss of access to schedules, basic patient information, encrypted communications platforms and radiology, and laboratory and pharmacy services, clinical outpatient care delivery was reduced by 40%. The infusion visit volume dropped by 52% in the first week and new patients could not access necessary services for timely diagnostic evaluation, requiring the creation of command centers to oversee ethical and transparent triage and allocation of systemic therapies and address new patient referrals. This included appropriate transfer of patients to alternate sites to minimize delays. Inpatient care including transitions of care was particularly challenging and addressing patient populations whose survival might be affected by delays in care.CONCLUSION:Oncology health care leaders and providers should be aware of the potential impact of a cyberattack on cancer care delivery and preventively develop processes to mitigate the impact.

Thrombocytopenia is a serious complication of MDS associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS.We conducted a phase 2 multicenter trial of ELT and LEN in adult patients with low or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic.52 patients were enrolled; mean age was 71 years (range 34-93). ORR in the ITT population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving HI-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. 15 patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematological grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT.ELT and LEN are well tolerated and effective in achieving hematological improvement in patients with low/intermediate-risk MDS.

As life expectancy for HIV patients improve, hepatocellular carcinoma (HCC) has become a non-AIDS defining illness with a high impact on morbidity and mortality of HIV-infected individuals. We sought to compare outcomes in HIV- versus non-HIV-infected patients treated for HCC at a multiethnic academic medical health system.A retrospective chart review of patients diagnosed with HCC from 1/1/2005 to 12/31/2016 was performed. Differences in characteristics among HIV and non-HIV subjects were assessed. Associations between HIV status, viral load, CD4 count, and overall survival (OS) were also assessed.We identified 915 subjects (842 non-HIV and 73 with HIV). HIV-infected subjects were younger, predominantly male non-Hispanic Blacks, and more likely to have HBV and HCV co-infection, and alcohol use at diagnosis compared to non-HIV counterparts. Stage, MELD score, Child-Pugh, and ECOG performance status were similar. HIV-positive patients received systemic therapy at significantly higher rates and liver transplantation for HCC at significantly lower rates than those without HIV. The actuarial 3- and 5-year overall survival (OS) for all patients was 48.3% and 39.4%. For HIV-infected subjects, 3- and 5-year OS was significantly worse at 36.8% and 28.3% compared to 49.3% and 40.4%, respectively, for non-HIV subjects (log rank p = 0.033).HIV-infected HCC patients have lower survival rates compared to those without HIV. Despite younger age and similar stage, MELD, and ECOG at diagnosis, HIV portends worse outcomes in patients with HCC.

Acute myeloid leukemia may present with significant dysmyelopoiesis within the peripheral blood smear and bone marrow aspirate. In the setting of Vitamin B12 deficiency, proliferation of a clonal population of malignant cells can become impaired, masking an underlying myelodysplastic or leukemic process. Typically, the cautionary tale warns against diagnosing acute myeloid leukemia before ruling out Vitamin B12 deficiency. Here we describe a patient who initially presented with pancytopenia and Vitamin B12 deficiency who, upon supplementation, developed overt acute myeloid leukemia. This case will highlight the importance of cytogenetic and molecular studies as essential diagnostic tools in patients with unique presentations.

Even though HIV is associated with worse prognosis in many malignancies, the clinical course of myelodysplastic syndrome (MDS) in HIV + patients has not been well studied. Determining the clinical presentation and outcomes of MDS in these patients would be important for future diagnostic strategies, as anemia and other cytopenias are commonly seen in HIV + patients. Unique data mining software was used to identify cases of MDS or AML in adult patients who were also HIV + at Albert Einstein/Montefiore Medical Center between 1 January 2003 and 1 January 2017. Using Chi-Square and Fisher's exact test, characteristics of the HIV + MDS patients were compared to 135 HIV - MDS patients from the same institution diagnosed between 1997 and 2011. Fourteen biopsy proven MDS patients were identified with concomitant HIV. HIV + MDS patients presented at a younger age (59 vs. 71 yrs

Optimal treatment of acute myeloid leukemia (AML) arising in elderly patients remains a challenge. FDA approval of Ivosidenib and Enasidenib, small molecule inhibitors of isocitrate dehydrogenase enzymes (IDH1 and 2) have opened new avenues of treatment. We present a 60-year-old woman with refractory AML, achieving complete response to the combination therapy of hypomethylating agent, Azacytidine with the IDH2 inhibitor, Enasidenib, and BCL2 inhibitor, Venetoclax. To our knowledge, this is the first case report of a patient with IDH2 mutated refractory AML achieving complete response to combination therapy with azacytidine, enasidenib and venetoclax.

Progressive multifocal leukoencephalopathy (PML) is a life-threatening opportunistic infection of immunomodulatory therapies. PML cases reported in PubMed (1995-2017) following stem-cell transplantation (HSCT) or chemoimmunotherapy (CIT) for hematologic malignancies were reviewed. We found 107 cases, 40% were HSCT recipients (32 allogeneic, 11 autologous) and 40% indolent lymphomas receiving monoclonal antibodies (mAbs). HSCT cases had longer time to PML diagnosis (10.8 vs. 4 months, p .001), higher proportion of PML therapy response (58% vs. 25%, p = .019), lower mortality rate (56% vs. 88%, p .001), and longer median survival (8 vs. 2 months, p .001). Outcome differences might be caused by selection bias as HSCT patients are most likely treated aggressively; however, time-dependent immune reconstitution might also contribute to their better prognosis. Increased use of mAbs and HSCT are associated with rising PML incidence in hematological malignancies, currently constituting the second largest vulnerable population after HIV-infected patients; further research is needed for its optimal treatment.

Introduction: Lenalidomide (LEN) is approved for treatment of Myelodysplastic Syndrome (MDS) with chromosome 5q deletion (del 5q) as it has shown to induce disease remission and transfusion independence in close to 65% of this population. For patients (pts) without del 5q, LEN has shown to reduce transfusion needs in one-quarter of pts, but its use is limited by significant thrombocytopenia, and pts with platelet counts (PLTs) Methods: Pts aged ≥18 years with low/int risk MDS per IPSS, or non-proliferative chronic myelomonocytic leukemia (CMML), with bone marrow blasts Results: 51 pts were accrued, with 44 evaluable pts. Of evaluable pts, most were male (70%), median age was 71 years (range 34-93). 42 (95%) pts had MDS and 2 (5%) CMML. 24 (55%) pts were low-risk per IPSS-R score. 28 (64%) pts were treatment-naïve and 16 (36%) had received ≥1lines of treatment, including erythropoiesis stimulating agents. 24 (55%) pts were assigned to arm A and 20 (45%) pts to arm B. ELT/LEN was well tolerated. Non-hematological grade 3-4 treatment-related adverse events were few, including G3 hyperbilirubinemia (7%), G3 transaminitis (2%), G3 diarrhea (2%), G3 arthralgias (2%). 2 pts had major bleeding events; there were 2 deaths, one attributable to pneumonia and one to gallbladder cancer. 1 of 31 pts who received ELT had a reversible increase in peripheral blasts while on treatment, and 1 pt had development of marrow fibrosis after 6 years of ELT. ITT analysis of total population (51) revealed an objective response (ORR) of 35%; ORR of 32% (9/28) in arm A (PLTs ≥50,000),and 39% (9/23) in arm B (PLTs 17 pts received ELT alone, among these ORR was 41% (7/17), with 29% achieving bilineage responses, 1 CR. 13 pts received LEN alone, ORR was 46% (6/13), of these 100% achieved RBC-TI. 14 pts received ELT/LEN combination, ORR was 36%, 2 (14%) achieved bilineage responses and 2 (14%) CR. There were 2 HIV-positive MDS pts, both achieved sustained CRs, one with ELT alone and one with ELT/LEN combination. Mean time to response was 9.4 wks (range 6-12.4) for ELT alone, 10.9 wks (range 2.4-16) for LEN alone, and 9.9 wks (range 2-20) for ELT/LEN combination. Mean duration of response was 102 wks for ELT (range 8-ongoing), 63 wks (range 25-ongoing) for LEN, and 66 wks (range 8.3-ongoing) for ELT/LEN as of last follow-up. Conclusions: Treatment with ELT/LEN demonstrates good efficacy with ORR of 40.9%, response durability and an acceptable safety profile for evaluable pts with low/int risk MDS. ELT can lead to single agent responses with an acceptable safety profile and sizable proportion of multilineage responses. One patient developed bone marrow fibrosis and one patient had a transient increase in blasts, hence, undermining these pre-existing safety concerns. Lastly, using our study schema 32% of pts were able to initiate or continue LEN achieving a 36% ORR whereas in prior studies these pts would have been excluded. Figure 1 Figure 1. Disclosures Yacoub: Agios: Membership on an entity's Board of Directors or advisory committees; Acceleron Pharma: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau. Gritsman: iOnctura: Research Funding. Shastri: Kymera Therapeutics: Research Funding; Onclive: Honoraria; GLC: Consultancy; Guidepoint: Consultancy. Verma: Celgene: Consultancy; Acceleron: Consultancy; Novartis: Consultancy; Stelexis: Consultancy, Current equity holder in publicly-traded company; Eli Lilly: Research Funding; Curis: Research Funding; Medpacto: Research Funding; Incyte: Research Funding; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company; GSK: Research Funding; BMS: Research Funding. OffLabel Disclosure: Lenalidomide has shown to be effective achieving RBC Transfusion Independence in Myelodysplastic Syndromes without deletion 5q Eltrombopag is a TPO-R agonist, its purpose in this trial is to evaluate if it would increase platelet counts in patients with Myelodisplastic Syndrome.

The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.7%; 17 out of 255; odds ratio, 3.14; 95% confidence interval, 1.64-6.03; P = 0.0006) after controlling for age, sex and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A, TET2 and other CH-associated genes. Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. In summary, the high burden of CH in WTC-exposed first responders provides a rationale for enhanced screening and preventative efforts in this population.

Introduction The World Trade Center (WTC) disaster exposed first responders to high levels of aerosolized carcinogens (Lioy et. al. Env. Health Perspect 2002). Clonal hematopoiesis is associated with exposure to smoking and genotoxic stimuli (Jaiswal et. al. NEJM 2014; Genovese et. al. NEJM 2015). We sought to determine its incidence in WTC-exposed first responders. We also assessed the effect of WTC particulate matter (WTC-PM) on genome integrity in vitro, and in murine studies. Methods Deep targeted sequencing was performed on blood collected from 481 first responders (429 WTC-exposed firefighters, 52 WTC-exposed emergency medical service workers) and 52 non-exposed first responders. Samples were analyzed for 237 genes mutated in hematologic malignancies and interpreted using reference databases. Non synonymous somatic mutations were annotated and analyzed. Results In the WTC-exposed cohort, 57 individuals with 66 somatic mutations of expected pathogenic potential were identified (overall prevalence 11.9%). In the non-exposed cohort, only one pathogenic mutation was found in the IDH2 gene (overall prevalence 1.9%). There was a strong association between increasing age and prevalence of mutations in the WTC-exposed cohort (Fig 1A). DNMT3A (16/66), TET2 (7/66), SF3B1 and SRSF2 (3/66 each) were the most common genes identified in the WTC-exposed cohort (Fig 1B). Median VAF was 12% and missense mutations were most frequent alteration. Aging, smoking, DNA repair and alkylating agent exposure related mutational signatures were observed with a cytosine to thymine (C→T) transition being most common. Next, we assessed the effect of WTC-PM on genome integrity and replication in vitro. WTC-PM that was collected in the first three days after 9/11 was used in concentrations mimicking exposure levels. Lymphocytes exposed to WTC-PM demonstrated a significant increase in phosphorylated H2AX foci accumulation, suggesting a DNA damage response (Fig 2). Since common fragile sites (CFSs) detect basal levels of stress in the cell, and activate DNA damage response (DDR), we profiled DNA replication dynamics at CFS-FRA16D at very high resolution using the single molecule analysis of replicated DNA (SMARD) assay. Treatment with WTC-PM significantly altered replication at two common fragile sites (regions 1 and 2 of FRA16D, Fig 3A) with replication pausing being observed at multiple sites (Fig 3B-I, white rectangles). Striking increase in replication initiation was seen, characterized as dormant origins activated to rescue replication pausing (Fig 3E, J). These alterations were accompanied by a corresponding increase in replication speed, conditions that lead to DNA replication errors and mutagenesis (Fig 3F, K). Next, we treated mice with WTC-PM via the oropharyngeal route to mimic first responder exposures, and then harvested and analyzed their bone marrow compartments. Significant expansion of hematopoietic stem cells (Kit+, Sca1+, Lineage-ve, KSL) was seen in WTC-PM treated mice (Fig 4A,B). Whole genome sequencing of sorted stem cells showed a significant increase in non-synonymous SNPs, deletions and indels in the WTC-PM treated samples when compared to control (Fig 4C-E). These genomic alterations were found to occur at low VAF throughout the whole genome, demonstrating widespread genotoxic effects of WTC-PM on hematopoietic stem cells in vivo (Fig 4F). Discussion We report a high burden of mutations in 11.9% (57/481) WTC-exposed first responders compared to the non-exposed cohort (1.9%, 1/52). The frequency of the somatic mutations was many fold higher than in previous studies (Jaiswal et. al. NEJM 2014; Genovese et. al. NEJM, 2015). In the 50-59 year age group, 10% of WTC-exposed individuals carried somatic mutations, compared to the frequency of 2.5% reported by Jaiswal et. al. for the same age group. Despite deeper sequencing performed in our study, the median VAF in our study was 12%, indicating that the difference in technique did not bias our study towards increased detection of small, subclinical clones when compared to previous studies. Furthermore, we demonstrate that WTC-PM can perturb DNA replication and increased genomic instability in vivo, potentially leading to higher burden of clonal hematopoiesis in WTC-exposed first responders. These results demonstrate adverse environmental exposures can be associated with a high rate of clonal hematopoiesis. Disclosures Landgren: Sanofi: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Other: IDMC; Theradex: Other: IDMC; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Fletcher:Genoptix/Neogenomics: Employment. Ebert:Broad Institute: Other: Contributor to a patent filing on this technology that is held by the Broad Institute.; Celgene: Research Funding; Deerfield: Research Funding. Steidl:GlaxoSmithKline: Research Funding; Celgene: Consultancy; Aileron Therapeutics: Consultancy, Research Funding; Stelexis Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Scientific Co-Founder; Pieries Pharmaceuticals: Consultancy; BayerHealthcare: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Will:Novartis Pharmaceuticals: Research Funding. Verma:Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria; BMS: Research Funding; Janssen: Research Funding.

Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20–30%. Anthracycline toxicities include the rare—but potential morbid—cardiotoxicity or leukemogenic effect, and the almost universal—but very distressing—alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer. Current literature supports that anthracyclines are not required for all patients with breast cancer and should be avoided in those with high cardiac risk. Recent results from the ABC trials suggest that anthracyclines should not be spared for patients with triple negative breast cancer (regardless of axillary node involvement) or HER2−/ER+ with significant node involvement. Based on current literature, for HER2-negative patients with low-risk breast cancer, anthracyclines could be spared with regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF) or docetaxel and cyclophosphamide (TC). Patients with intermediate or high-risk breast cancer should be considered for anthracycline-based regimens based on other factors such as age, comorbidities, tumor grade, lymphovascular invasion, and genomic profiling. Patients with HER2-positive breast cancer with low risk could be treated with paclitaxel and trastuzumab. For the remaining patients with HER2 overexpression, while docetaxel, carboplatin, and trastuzumab (TCH) has demonstrated to improve disease-free survival (DFS), anthracycline-containing regimens should be discussed, especially for those with very high-risk breast cancer. Although several biomarkers, such as topoisomerase II (TOP2A) and chromosome 17 centromeric duplication (Ch17CEP) have been proposed to predict benefit from anthracycline regimens, further research is required to delineate their proper utility in the clinical setting.

TheKytococcusgenus formerly belonged toMicrococcus. The first report of aKytococcus schroeteriinfection was in 2002 in a patient diagnosed with endocarditis. We report a case of central line associatedKytococcus schroeteribacteremia in a patient with underlying Hairy Cell Leukemia.Kytococcus schroeteriis an emerging infection in the neutropenic population and in patients with implanted artificial tissue. It is thought to be a commensal bacterium of the skin; however, attempts to culture the bacteria remain unsuccessful. There have been a total of 5 cases (including ours) ofK. schroeteribacteremia in patients with hematologic malignancies and neutropenia and only 18 documented cases in any population. Four of the cases of bacteria in neutropenic patients have been fatal, but early detection and treatment could make a difference in clinical outcomes.

INTRODUCTION: There is a lack of data on early mortality in aggressive lymphomas, particularly HIV-related lymphomas. Patients who present with advanced disease and poor performance status are at a higher risk of adverse outcomes and are not offered clinical trial enrollment. Factors that may contribute to early mortality have not been delineated. In this retrospective analysis, we sought to identify causes and predictors of early mortality, occurring within 180 days of index diagnosis, in patients with HIV-positive and negative DLBCL, at an academic medical center. METHODS: We reviewed an electronic database to identify patients with a diagnosis of HIV-related DLBCL, treated at our center between January 1, 2005 and December 31, 2017. We further identified patients with non-HIV positive DLBCL diagnosed from January 1, 2015 to December 31, 2017. Data on patient demographics, clinical outcomes and treatment was collected. We defined early mortality as those patients who died within 180 days of diagnosis. RESULTS: HIV-NEGATIVE DLBCL: There were 103 HIV-negative patients with DLBCL, with a mean age of 65 years. N=17 (16.5%) patients expired within 180 days of diagnosis. In univariate analysis, factors predicting increased risk of mortality included poor ECOG performance status (PS) 3-4, presence of B-symptoms and higher international prognostic index (IPI) scores (Table 1). In multivariate analysis, poor PS (HR 4.86, p HIV-POSITIVE DLBCL: We identified 82 patients with HIV-positive DLBCL and divided patients into Cohort A (N=25) patients who expired within 180 days and Cohort B (N=57), patients who were alive beyond 180 days. 9 patients died within the first 30 days, 20 patients within 90 days and 25 patients within 180 days of index diagnosis. Both groups predominantly consisted of African-Americans with advanced stage DLBCL with a mean age of 53 and 48 years respectively (p=0.02). In univariate analysis, more patients in Cohort A had Stage 3-4 DLBCL (100% vs. 86%), poorer ECOG PS of 3-4 (52% vs. 7%), higher IPI scores (56% vs. 11%), lower CD4 counts (median of 70 cells/uL vs. 140 cells/uL) and higher LDH (544 U/L vs. 270 U/L). In multivariate analysis, we found that poor ECOG PS (HR 2.4, p We wanted to examine whether the time period of diagnosis affected mortality from HIV-related DLBCL in patients. Group 1 patients were diagnosed from January 2005 to December 2010 (N=20) and Group 2 from January 2011 to December 2017 (N=29). We found that in Group 1, 50% of patients died from progressive disease and 15% of patients died from an acute event. Meanwhile, in Group 2, 38% of patients died from progressive disease, and 52% died from an acute event. Sepsis was the most common acute event in both groups. CONCLUSION: Preventing early mortality in aggressive lymphomas is crucial to improving overall survival. For patients with non-HIV related DLBCL, we found poor ECOG PS and presence of B-symptoms to be predictors of early mortality. In patients with HIV-positive DLBCL, poor ECOG PS, higher LDH and older age were contributing factors. The leading cause of death in both HIV-positive and HIV-negative patients (2011- 2017) was sepsis followed by progressive disease at 180 days after diagnosis. Although sepsis is a major factor contributing to early mortality and morbidity, it is preventable with prophylaxis against opportunistic infections. In order to decrease sepsis related mortality, we propose early initiation of antimicrobial therapy in patients at high risk based on independent clinical variables identified in this study. A prospective study preventing sepsis in high risk patients is warranted to decrease early mortality in patients with aggressive lymphoma. Disclosures Janakiram: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Introduction: As people with HIV live longer, the epidemiology of plasma cell disorders (PCD) including MGUS, smoldering myeloma and Multiple myeloma (MM) becomes relevant and remains unknown. Moreover, patients with HIV have a higher incidence of monoclonal proteins which may not be related to an underlying lymphoproliferative disorder[1, 2] . There are mostly anecdotal reports and very few studies in HIV myeloma[3]. A retrospective study of 10 patients with HIV+ve symptomatic MM reported possible therapeutic benefit of ART and reported better overall survival of HIV+ve MM on ART as compared to HIV -ve MM. There is a paucity of data in PCD in this population whose incidence can be expected to increase globally. We conducted a single-institution retrospective study to look at the incidence of PCD. Methodology:We reviewed an electronic database of patients with HIV related PCD treated at Montefiore Medical Center between 2001 and 2018. All patients with a new diagnosis of PCD between January 1 2001 to July 15 2018 were identified. Data on patient demographics, HIV status, clinical outcomes (including mortality) and therapy was collected. Results: Between 2001 and 2018, 14438 patients were identified with HIV and 1986 patients had a monoclonal band in SPEP (13.8%). Based on our previous study, patients who had a definitive monoclonal band or suspected MM underwent a BM biopsy. 34 patients were diagnosed with PCD --MGUS 16 (47.05%), Smoldering MM 1 (2.94%), MM 16 (47.05%) and Primary plasma cell leukemia (PCL) 1 (2.94%). The majority of the patients were AA consistent with demographics of the Bronx. Interestingly HCV co-infection was identified in 50% (n=17) of patients and HBV co-infection was present in 15% (n=5) patients. The median CD4 count was 381 (12-1080), median viral load 237 (0-501534) and 53% patients were on ART at the time of diagnosis. The median time from HIV diagnosis was 13.9 (-2.8 to 29) years. In patients with MGUS the predominant heavy chain involvement was IgG, the median protein on SPEP was 1.1 g (0.7-1.9 g) and percentage of BM involvement was 5% (2-10%). In patients with MM IgG was the predominant heavy chain involved. On presentation, ISS Stage was Stage I in 2 patients (15.4%), 4 (30.7%) had at least Stage 2, 7 patients (53.9%) had stage 3. On presentation, 10 (58.8%) patients presented with anemia, 10 (58.8%) presented with renal impairment (Cr>=1.3), 16 (94.1%) presented with bone lesions, 6 (37.5%) presented with hypercalcemia. 5 patients (34.6%) had extramedullary presentation including 1 patient (2.9%) with PCL, 2 (5.8%) with anaplastic plasmacytoma. All patients were treated with an imid or bortezomib based regimen and there were no unusual side effects in these patients. 5 patients (29.4%) underwent autologous stem cell transplant with successful outcomes. Discussion: The prevalence of a positive SPEP is 13.8% in patients with HIV and the prevalence of plasma cell dyscrasias (PCD) in our population is 0.02%. A previous study from this cohort[2] showed that approximately 6.4% of patients with a positive SPEP developed hematological malignancy and all patients with a faint monoclonal band had lymphoma (70.5%) and those with a definite monoclonal band had myeloma (29.5%). Even though prevalence is less than the general population rate of 3%, as patients with HIV live longer this number may increase. In our study there was a high rate of co-infection with HCV in patients who had a PCD and this needs further investigation to determine causality. PCD developed at a median of 13.9 years after HIV diagnosis. The ISS staging distribution in patients presenting with myeloma is consistent with non HIV myeloma. People with HIV tolerate standard imid or proteasome inhibitor based triple drug therapy and have successful outcomes with autologous transplantation. This is the largest cohort and report describing PCD in HIV population. References:Jou, E., et al., Viral co-infections and paraproteins in HIV: effect on development of hematological malignancies. Ann Hematol, 2016. 95(4): p. 575-80.Jou, E., et al., Retrospective study of the prevalence and progression of monoclonal gammopathy in HIV positive versus HIV negative patients. Hematol Oncol, 2017. 35(1): p. 64-68.Li, G., et al., A retrospective analysis of ten symptomatic multiple myeloma patients with HIV infection: A potential therapeutic effect of HAART in multiple myeloma. Leukemia Research, 2014. 38(9): p. 1079-1084. Disclosures Janakiram: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Background: Multiple Myeloma (MM) represents 1.8% of all new cancers in the United States and is the second most common hematologic malignancy in the US with 30,000 new cases/year. The highest incidence is amongst African Americans (AA) (SEER, 2018). Increased use of autologous stem cell transplant (AHSCT) as well as introduction of proteasome inhibitors (PIs) and immunomodulatory agents (iMiDs) have led to an improvement in overall survival (OS) from 35.6% between 1998-2001 to 50.7% in 2008-2014 (Child et al. 2003; Pulte et al. 2014). Despite these improvements, outcomes in MM are heterogeneous and are influenced by sociodemographic factors like race and ethnicity, disease biology (laboratory markers, cytogenetics) and access to transplantation (Al-Hamadani, Hashmi, and Go 2014; Ailawadhi et al. 2016). Several large population-based studies report that Hispanics have low stem cell utilization rates, limited access to novel therapeutics and clinical trials as well (Ailawadhi et al. 2018; Costa et al. 2015; Schriber et al. 2017; Pulte et al. 2014). Hence, outcomes for Hispanics and AA lag behind non-Hispanic Whites as well (Pulte et al. 2014). We wanted to evaluate outcomes of MM patients at Montefiore Medical Center where AA and Hispanics have access to novel agents and therapeutics, and most of whom hail from a poor socio-economic status. Methods: We obtained a cohort of patients diagnosed with MM between 1/1/2000-12/31/2017 from the Montefiore Medical Center Cancer Registry database via Clinical Looking Glass software. Socio-demographic characteristics including self-reported ethnicity, date of diagnosis, histology, laboratory parameters (hemoglobin (Hgb), creatinine (Cr), albumin (Alb), serum lactate dehydrogenase (LDH)) within 30 days of diagnosis were obtained. Ethnicity and race variables were condensed to Hispanics, Non-Hispanic Whites (NHW) and Non-Hispanic African Americans (NHAA). Charlson comorbidity score and its age-adjusted version were calculated. Primary payor (Medicaid, Medicare, private insurance or self-pay) was identified for each patient. Descriptive statistical analysis was performed using STATA 15.1 statistical software. OS was estimated using the Kaplan-Meier method and HR and corresponding 95% confidence intervals (CI) were estimated using the cox proportional hazard model. All the variables in the Cox proportional hazard ratio model fulfill the proportional hazard assumption. Results: We identified 1630 patients during the study period; 1502 patients were available for analysis (Table 1) The mean age of diagnosis was 66 years, and NWH were diagnosed at older age when compared to Hispanics or NHAA (71 vs 64 vs 66, p=0.001) respectively. Hispanics had a higher proportion of Medicaid affiliation. The baseline mean Hb (p=0.02), Cr (p=0.02) and LDH (p=0.09) were different; however this difference is unlikely to be clinically relevant (Table 1). Median survival for the cohort was 63 months (95% CI: 59-69). Hispanics had better mean OS (118 months, (95% CI 96-128) as compared to NHW (49 months, 95% CI 40-68)) and NHAA (60 months, 95% CI 53-66) and others (32 months, 95% CI 21-46) (Figure 1). After controlling for age at diagnosis, gender, socioeconomic status, modified Charlson age score, race had a statistically significant impact on the outcome, with NHW (HR-2.01) and NHAA (HR 1.77) having poorer survival when compared to Hispanics (P Conclusion The study cohort is significantly different to prior reports, with a higher rate of NHAA and Hispanics. Hispanics had a higher percentage of Medicaid as primary payor. Contrary to prior reports, we show that with access to novel agents and transplantation, MM in Hispanics has a better OS than AA and NHW. We also show that NHAA (41%) despite being diagnosed at a younger age than NHW continue to have poorer outcomes than Hispanics. Further characterization including risk stratification and cytogenetics is underway to identify factors leading to better and worse outcome in Hispanics and AA respectively. Disclosures Janakiram: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Purpose. Acute antibody-mediated rejection, a complication of cross match positive and sensitized renal transplants, occurs despite the use of standard desensitization protocols. Rescue therapy consists of plasmapheresis and intravenous immunoglobulin (IVIg). In patients with preformed donor specific antibodies, rejection can be aggressive. We report here a case in which laparoscopic splenectomy was added to the standard rescue regimen.Case Report and Results. A 40-year-old Hispanic female with end stage renal disease had been receiving hemodialysis. The patient had numerous class 1 unacceptable antigens. She was scheduled to undergo an incompatible 1-1-1 mismatch living related donor kidney transplant. Preoperatively, the patient received plasmapheresis, IVIG, and thymoglobulin. There was good graft function until postoperative day 5. At that point, worsening renal function was noted. Renal biopsy was consistent with AMR. The patient became anuric and dialysis was initiated. To salvage the transplant, the patient underwent laparoscopic splenectomy. Postoperatively, renal function improved. Two years after transplant, the patient continues to have excellent graft function.Conclusion. In a small but significant number of renal transplants, antibody production occurs at a rate that traditional treatments are unable to reduce effectively. Based on our experience, the addition of splenectomy to standard rescue therapy can salvage renal transplants.

e16565 Background: Treatment (TX) of breast cancer (BC) in elderly (E) patients (pt) can be problematic due to the increased co-morbidities (CM), multiple medications, and cognitive dysfunction related to age. Due to this many E pt are less likely to have standardized treatment (TX). This study was undertaken to assess if pt over the age of 70 diagnosed with BC received TX based on NCCN guidelines and what CM led to selection of therapies. Methods: A retrospective review at a tertiary care medical center identified 108 pt over the age of 70 with BC from 2001-2011. Clinical data was obtained regarding race, age, stage (ST) at diagnosis, TX, CM, estrogen receptor (ER), progesterone receptor (PR), and HER2neu receptor (H2N) status. Results: Of the 108 pts, 22% were Caucasians, 66% were African-American, 3% Asian, 6% Hispanic, and 2% other. The age range was 70 to 96 years, mean of 75. Staging was as follows: 23% DCIS, 24% ST I, 28% ST II, 9% ST III, and 7% ST IV. 66% were ER positive (+), 60% PR+, and 87% H2N negative. H2N status was not available on 9% of the pts. In 92% of the pt surgical intervention (SI), either lumpectomy (L) with radiation therapy (RT), or mastectomy (M) was done (see table below). 8% of pt either refused SI or were lost to follow-up. ER/PR+ pt hormone therapy (HT) was started in 95% of pt. 3% of ER/PR+ pt refused HT. In stage II and III 60% of pt had adjuvant chemotherapy (CT), only 5% refused CT. In ST IV 30% had HT alone, 50% with CT and HT, and 25% with RT to chest wall for local recurrence. Only 23% of H2N positive pt received Herceptin. 52% of the CT used in stage II and III was cyclophosphamide, methotrexate, fluorouracil (CMF). CM in the CMF pts were as follows 90% cardiovascular disease (CAD), 53% arthritis (AR), 13% history malignancy, and 13% pulmonary disease. In the pt who refused SI, and/or CT the most common CM were 70% CAD, 50% AR, and 25% dementia. Conclusions: The majority of the E BC pt in this cohort had significant CM that made TX challenging. Some pt were not offered appropriate CT (i.e., trastuzumab) due to CM. Age impacts BC TX, but should not hinder the pt receiving optimal tx. Further studies with women over the age of 70 with BC is required to determine the most appropriate TX in this subset of pts. [Table: see text]