ALBERT

Description: Introduction: Complete remission (CR) is an important endpoint after cytarabine plus anthracycline [7+3] induction therapy in Acute Myelogenous Leukemia (AML). Even though CR is observed in about 50-90% of unselected European Leukemia Network 2017 (ELN-2017) patients (pt), factors such as age 〉65 years, complex karyotype, and adverse mutations (RUNX1, ASLX1, TP53, FLT3 ITD high, KMT2A, secondary AML), leads to inadequate blast eradication. Early response to induction is a predictor of subsequent complete remission (CR). Bone marrow day 14 [D14] inform pt with early inadequate leukemia eradication [blast 〉10%] who are suitable for re-induction, a strategy that seeks to facilitate conversion to CR or CR with incomplete hematologic recovery (CRi), secure potential allogenic transplantation and reproduce superior outcomes. In this study, we investigated the clinical outcome of an unselected ELN-2017 AML cohort with inadequate D14 marrow response. From the subgroup of patients exhibiting sub-optimal response (SOR), we examined the odds and predictors for subsequent achievement of CR/CRi for those patients who did not receiving immediate re-induction therapy. Additionally, we evaluated the effect of subsequent CR/CRi achievement on survival. Methods: With prior IRB approval, 160 AML pt diagnosed with AML from 1995 to 2017 within Baylor College of Medicine institutions were evaluated. Kaplan-Meier method was used to estimate overall survival (OS) among pt achieving D14 10% blast in an unselected ELN-2017 AML cohort and pt exhibiting 〉10% blast in D14 marrow with and without CR/CRi. Logistic and cox regression analysis in SOR pt [1] attaining subsequent CR/CRi and [2] OS, respectively, was performed to investigate multiple independent variables with predictive value for the 2 above outcomes. Results: 68/160 (42.5%) of pt had available D14 [early assessment] and sequential day 30 marrow for CR/CRi evaluation. Among 68 unselected ELN-2017 AML pt with D14 marrow for CR/CRi assessment, 42/68 (61.7%) and 26/68 (38.2%) had D14 marrow blasts 〈 and 〉 10%. Median age was 57 y (range 27-73) and 59 y (range 24-89), respectively, p= 0.74. OS was 459 d vs 169 d in pt with D14 marrow 10%, at day 14 (p=0.001 95% CI 0.2-0.9) [Fig 1A]. CR/CRi was observed in 36/42 (90%) and 10/26 (38.7%) of pt with D14 marrow 10%, respectively, p=0.0005. After controlling for traditional high-risk factors including WBC, age, platelet count, RDW, de novo v secondary AML, only ELN-2017 classification [fav vs unfav and intermediate vs unfav, p= 0.0026 and p=0.01] retained impact on survival. In pt with SOR, we performed second analysis to investigate survival among pt with and without subsequent CR/CRi achievement who did not receive re-induction [Fig 1B]. 16/26 (62.5%) of pt with SOR failed to achieved CR/CRi. OS was 333 d vs 109 d for pt with CR/CRi vs those without CR/CRi [p=0.002, 95% CI 2.6-3.4]. Logistic regression identified in pt with CR/CRi vs those without CR/CRi that: [a] age [63.1 vs 43.6 y-p=0.001]; [b] lower platelet count [47.1 vs 83.1 K/uL-p=0.03]; [c] higher absolute monocyte count (AMC) [3.7 vs 0.41 K/uL-p=0.04]; [d] increased RDW [18.3 vs 14.7-p=0.004] and [e] high BMI [31 vs 24.1-p=0.0003] were significantly associated with failure to achieve CR/CRi. Typical complex karyotype and initial marrow blast % were not associated with subsequent CR/CRi achievement. However, in pt with SOR, lack of high-risk mutations [P53, RUNX, FLT3-ITD, U2AF1] was significant associated with CR/CRi, [40% v 62.5%, p= 0.0004]. Cox proportional regression model showed significant impact on survival for high-risk mutations and higher BMI in survival. Conclusion: In our retrospective study, despite 38.7% of patients with detectable D14 residual leukemia achieved CR/CRi without re-induction, failure to attain CR/CRi was frequently observed after SOR. Advanced age, lower platelet count, higher AMC, RDW and BMI predict failure to achieve CR/CRi status in patients exhibiting initial SOR. Lack of high-risk mutation was a strong predictor for CR/CRi achievement. Our study is novel by suggesting that a combination of pre-induction and "early post-induction" variables facilitate recognition of high-risk AML subgroups requiring re-induction or alternative novel therapy via clinical trials. Disclosures Yellapragada: Takeda: Research Funding; Novartis: Employment; Celgene: Research Funding.

Description: Introduction Iron plays a critical role in patients with multiple myeloma (MM). The limited availability of iron to the developing erythroid precursors results in the characteristic anemia so frequently seen in these patients. Moreover, iron is also a determinant in growth of the malignant plasma cells that makes it one of the critical factors in progression of the disease. Iron is a key component in success of erythropoietin (EPO) therapy that is often used to maintain hemoglobin (Hb) level of 〉10g/dL in patients with MM. International Myeloma working group (2011) advised transfusing IV iron to aid in success of EPO therapy. However, apart from determining the iron stores on bone marraow aspirate, there is hardly any reliable clinical or lab indicator of the iron stores in the body. The utility of various iron indices in determining the bone marrow iron stores remains anecdotal. In this study we aim to determine the relation between iron indices and iron level in the bone marrow of patients diagnosed with multiple myeloma. Methods A total of 268 multiple myeloma patients, diagnosed from 2004 to 2015, were identified from tumor registry of John H. Stroger Jr. Hospital of Cook County, Chicago. Accuracy of ferritin, iron level, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and transferrin saturation (TSAT) was evaluated using receiver operating characteristic curves (ROC). Out of sampled patients, 167 patients had a concurrent bone marrow biopsy and aspirate, serum ferritin and iron panel, and were included in ROC analyses. Results The study population consisted of 57% African-Americans, 18% Caucasians and 16% Hispanics. Median age was 61 years and 51% were females. Past history was significant for hypertension (48%), diabetes (31%), co-existing inflammatory conditions (18%), smoking (25%), alcohol abuse (17%) and illicit drug abuse (8%). Median hemoglobin, mean corpuscular volume (MCV), leukocytes and platelets were 10g/dL, 90.3fL, 6,200/mcL and 219,500/mcL respectively. Bone marrow aspirates for iron were rated as absent (37%), mild/moderate (18%) and adequate/normal (45%). Anemia was found in 79% of males (Hb

Description: Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by bone marrow failure and a propensity to progress to acute myeloid leukemia (AML). A core component of the underlying pathogenesis in MDS is deregulation of inflammatory cytokines, such as tumor growth factor-β (TGFβ), which impact the function of immune cells and hence their capacity to mount anti-infective or anti-tumor responses. However, little is known about antigen-specific T cell function in patients with MDS. We hypothesized that virus-specific T cell (VST) function might be preserved in patients with MDS, and that the functional capacity of T cells reactive against tumor-associated antigens aberrantly overexpressed by clonal MDS cells such as Cyclin A1 (CCNA1) and Proteinase (PR3) might also be preserved and exploited for immunotherapeutic purposes. Following informed consent, we collected peripheral blood samples from 10 patients (pts) with MDS and 17 healthy donors. Most pts (9 out of 10) were transfusion dependent and 3 subsequently underwent an allogeneic HSCT. Table 1 summarizes the other clinical characteristics, karyotypic and mutational profile at the time of blood collection. Compared with T cells isolated from healthy donors, MDS patient-derived T cells had a similar CD4 to CD8 ratio (1.5-2.5:1 for healthy donors and 3:1 for MDS pts), but displayed a more exhausted profile at baseline (CD3+TIM3+: 1% in healthy donors and 5% in MDS pts) and produced higher levels of inflammatory cytokines [IFNγ (18±3pg/ml vs 36±16pg/ml, healthy donor vs MDS; p=0.12), and IL-8 (56±32 vs 704±446 pg/ml, p=0.01)]. Next, to assess the capacity of MDS pts to mount ex vivo functional virus-directed responses, we stimulated patient-derived PBMCs (n=5) with overlapping peptide libraries (pepmixes) spanning immunogenic AdV, CMV, EBV, BK and HHV-6 antigens. Similar to healthy donor-derived T cell lines (n=5, 3 specific for 4 viruses and 2 for 5 viruses), all 5 MDS patient-derived lines demonstrated specificity for one or more of the target viruses (1 for 5 viruses, 1 for 4, 2 for 3 and 1 for 1 virus) as observed by IFNγ ELISpot assay with comparable magnitude (range Adv: 43-730 vs 384-941 in healthy donors, CMV: 0-1599 vs 0-3002, EBV: 0-1486 vs 0-541, BK: 0-839 vs 38-275 and HHV6: 0-794 vs 5-407 SFU/2x105 cells, respectively). We next examined the feasibility of expanding autologous MDS-antigen directed T cell products (n=10) to determine whether an adoptive immunotherapeutic approach might be applicable for MDS treatment. Thus, we exposed patient-derived PBMCs to autologous dendritic cells (DC) loaded with pepmixes spanning 6 MDS-associated antigens (CCNA1, survivin, WT1, PRAME, PR3 and NYESO1). After 3 rounds of stimulation, the products obtained were predominantly CD3+ T cells (mean 88±1.3%) that were polyclonal (CD4: 46±5% and CD8: 41±4%) containing predominantly memory T cells (TEM: 36±6% TCM: 37±5% and Tnaïve =13±3%). Six lines (60%) showed specific recognition to at least one of the target antigens: 4 lines specific for PRAME, 1 for CCNA1, 1 for WT1 and 1 for NYESO1 (range 0-40, 0-184, 0-1386 and 0-179 SFU/2x105 cells, respectively by IFNγ ELIspot). T cell lines were capable of specifically secreting multiple effector cytokines in response to targets (TNFα: 12% and IFNγ: 16% in response to PRAME in a representative patient-derived T cell line). Furthermore, this line was capable of killing PRAME+ targets in a 4hr 51Cr release assay [60% specific lysis, E:T 20:1]. In conclusion, functional virus-directed T cell immunity in patients with MDS is preserved, potentially explaining the lower rates of viral reactivation seen in these patients compared with other infections. Moreover, T cells specific for MDS-expressed tumor antigens can also be successfully expanded ex vivo from patients. Taken together this raises the possibility of applying an adoptive immunotherapeutic approach for the treatment of MDS. Disclosures Ramos: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding. Leen:Allovir: Consultancy, Other: Cofounder, Ownership Interest; Marker Therapeutics: Consultancy, Other: Cofounder, Ownership Interest.

Description: Introduction: The incidence of bone marrow involvement (BMI) in patients diagnosed with Hodgkin Lymphoma (HL) is relatively low varying from 4-14% in different series occurring mainly in patients with advanced disease (stage III-IV). Ann Arbor staging system with Cotswolds modification in 1989 recommend staging bone marrow in patients with clinical stage III-IV and stage II patients with adverse risk features. It’s utility is now questionable and no longer recommended by many authors as it does not alter the way patients are managed. The advent of 18F-fluoro-2 –deoxy-D-glucose positive emission tomography (FDG-PET) scan use in the staging of patients has improved the prediction of possible bone marrow involvement obviating further the need for bone marrow biopsy. While BMI is said to be an independent prognostic factor in the survival of patient with HL, more studies have shown that BMI alone in patients with Stage IV disease does not influence survival or freedom from disease progression. Because staging bone marrow biopsy (BMB) use in HL varies from one institution to another, we performed a retrospective review in our institution in order to determine its incidence, risk factors and effect in the management of patients. Methods: We performed a retrospective search in John H Stroger, Jr. Hospital database of patients with HL seen from 2004 to 2013. 237 adult (18yr and above) patients were screened. 185 patients had BMB done as part of work up. Results: BMI was detected in 21%(38 of 185) of patients who had BMB as part of work up. M:F ratio was 2.5:1. Mean age was 39.8 +/- 11.5yrs. 51%(95 of 185) of patients who had BMB had advanced disease. 94%(33 out of 35) of patients with BMI had advanced disease prior to BMB. 3 patients with BMI were incompletely staged. Advanced disease was significantly more likely to be associated with BMI than early stage disease (OR 20.2 95% CI 4.6-87.6 p=0.0001). Less than 1%(2 out of 78) of patients with early stage disease were upstaged .The 2 patients that were upstaged had Stage IIB disease prior to BMB.38%(14 of 37) of patients with BMI were HIV positive which was higher compared to 12%(16 of 129) of patients without BMI that were HIV positive (OR 5.8 95% CI 2.4-14.0 p=0.0001). 5 of 38 patients with BMI had staging FDG-PET and all showed positivity in the skeletal system. Patients with BMI in our review were managed with 6-8cycles of chemotherapy (CT)-Adriamycin, Bleomycin, Vinblastine and Dacarbazine regimen (ABVD). 5 cases were relapsed disease. 4 of these patients with relapsed disease received Platinum/Gemcitabine regimen and one patient received Mechlorethamine, Vincristine, Procarbazine and Prednisone regimen (MOPP). Radiation Therapy (RT) was part of the management in 4 patients done for cord compression (2), bulky mediastinal disease (1) and for residual disease after chemotherapy (1). Conclusions: The incidence of BMI was high in our retrospective review compared to other series, however majority of involvement were in patients with advanced disease as in most series. Patients were rarely upstaged from early stage to advanced stage with bone marrow biopsy. This occurred in less than 1% in our retrospective review. Staging FDG-PET although done in few of our patients with BMI was predictive. Management of these patients was not significantly altered based on BMI. They were managed mainly with CT. RT needed in some of these patients was justified (cord compression, and bulky mediastinal disease). RT for residual disease is not a standard of care. Risks factors identified for BMI includes advanced disease and associated HIV infection. BMB does not alter patient management and its sole prognostic significance in patients with stage IV disease is controversial. It is therefore not necessary in the staging of newly diagnosed patients with HL. Disclosures No relevant conflicts of interest to declare.

Description: Background: Conventional risk factors for inferior outcomes in polycythemia vera (PV) include elevated hematocrit, white blood cell (WBC) count, age, and abnormal karyotype. Weight loss adversely impacts survival in cancer patients. JAK2 myeloproliferative neoplasms (MPN) upregulate tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8 and induce decreased leptin levels leading to weight loss. The impact of weight loss in PV patients receiving best supportive care (i.e. frontline hydroxyurea [HU] therapy, phlebotomy) on overall survival (OS) is largely unknown. In this study, we seek to investigate: (1) differential effect on survival for weight loss, and (2) variables with predictive value for weight loss among JAK2 inhibitor-naïve PV patients. Methods: After IRB approval, 46 patients at the Michael E. DeBakey VA Medical Center diagnosed with PV between 2000 and 2016 were selected for analysis. Our outcome of interest was OS among PV patients exhibiting weight loss versus patients who maintained, gained weight or had minor weight loss. To objectively estimate weight changes overtime, the difference between baseline BMI [BMI-B] at the time of diagnosis and BMI at last follow-up (BMI-L) was obtained for each patient. Survival analysis was performed for PV patients exhibiting more than 10% weight loss (〉10%) versus all other patients (less than 10% loss, stable and increased weight) (10% BMI loss and 27.7 for PV patients exhibiting 10% BMI (10.9 vs 7.6 K/uL, p=0.08). Median Hemoglobin (Hb), hematocrit (Hct) and ferritin were intriguingly lower in the 〉10% loss group at 16 vs 18.3 g/dL (p=0.01), 49.3 vs 54.2% (p=0.04) and 29.8 vs 50.6 ng/mL (p=0.09) respectively, while median RDW was higher at 18 vs 15.1% (p=0.01). OS was 9125 days vs 5364 days, in patients with 10% BMI loss, respectively (p=0.02, HR=0.20; CI 95% 0.04-0.84) (Figure 1). On multivariate analysis, age (hazard ratio [HR], 1.34; p