ALBERT

Description: Background Treatment related toxicity complicates outcome in elderly patients with AML (Estey et al. Blood. 2006). Conventionally, 7+3 induction (anthracycline plus cytarabine) results in Complete Remission rate of about 30%. Regimens with less toxicity, such as 10-days (d) schedule of DAC, seem promising with CR rate of 47% (Blum et al. PNAS. 2010). In secondary MDS derived AML, response prediction could be derived from mutation status in epigenetic modifiers (IDH1, IDH2, DNMT3 A, TET2), transcriptional regulators (RUNX1, CBL), and genes in spliceosome machinery, such as SF3B1 and SRSF2 (Husseinzadeh et al. American Society of Hem Meeting. Abstract # 1698. 2012). IDH-1 mutation is known to induce hypermethylator phenotype (fig 1) (Figueroa et al. Cancer Cell. 2010) and might be present in conjunction with SRSF2 mutations, an unique unreported molecular subset, feasible for exploring azanucleoside response prediction. Herein, we report a case of trisomy 8 MDS derived IDH1 and SRSF2 mutated AML who underwent rapid morphological blast differentiation in the context of acute differentiation syndrome while treated with 10 days (d) of hypomethylating dose of DAC. Methods A 61-year-old male with performance status (PS) = 3 presented with leukocytosis of 18.9 K/uL (peripheral blast 90%). He had a history of low-grade MDS diagnosed 2 years before  AML transformation. After morphological confirmation of M5 AML, fluorescent in situ hybridation (FISH) revealed 81% nuclei with trisomy 8. Extracted DNA was tested with a custom-designed Leukemia Cancer Gene Mutation Panel using AmpliSeq™ technology and showed IDH1 c.394C〉T(p.R132C) mutation (Fig. 2B) and c.284C〉T(p.P95L) mutation of SRSF2 gene (Fig. 2C). DAC was initiated at 15 mg/m2 for a total of 10 days every 28 d cycle. Results By day 5 of cycle (C)1 of DAC treatment, brisk and significant rebound leukocytosis of 60 K/uL  (Fig. 3) was observed, along with shortness of breath, hypoxemia and radiological evidence of floppy bilateral pulmonary infiltrates suggestive of acute-like differentiation syndrome. In addition to broad-spectrum antimicrobial and antifungal, dexamethasone at 4 mg intravenously (IV) every 8-hour (h) and hydroxyurea at 1 g orally every 8 h resulted in progressive normalization of peripheral blood count and hypoxemia after 48 h. Patient (pt) recovered from C1 and proceeded with C2 of treatment. A similar episode of brisk/robust leukocytosis was observed by day 5 of C2 requiring dexamethasone and hydroxyurea. Progressive morphological differentiation was observed to full mature and morphologically normal monocytes and neutrophil (Fig. 4). Pt expired as result of severe clostridium difficile colitis during C3 of DAC. Conclusions In our case, we observed robust acute differentiation syndrome characterized by rapid increase of WBC, shortness of breath and hypoxemia associated with azanucleoside treatment. Beside a novel association of IDH-1 and SRSF2 mutations, acute differentiation might suggest potential feature for azanucleoside response phenotype. Our case adds body of evidence of connection between epigenetic regulator and spliceosome mutations. Further studies on the impact of dual mutations in epigenetic reprogramming, leukemia transformation, and azanucleoside response will allow improved decision algorithm and therapeutic design. Disclosures: No relevant conflicts of interest to declare.

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: Background Myelodysplastic syndrome (MDS) is an inflammatory heterogeneous group of myeloid disorders with variable risk for acute myeloid leukemia (AML) conversion. Recent reports highlight that mutations [i.e. TET2, DNMT3A, AXSL1] configurate not only risk for malignant conversion in "healthy elderly individuals" but also 'directly' participate in coronary artery disease [CAD] development. TET2 clonal hematopoiesis [TET2 CHIP] accelerates atherosclerosis in mice via monocytic inflammatory amplification. Indeed, germ-line DNMT3A human disease phenocopy obesity and neurocognitive abnormalities suggesting that a more complex, but still poorly characterized cardiometabolic risk, probably originates from patient predisposition and somatic mutation acquisition. We seek to originate a cross-sectional "proof of concept" for quantifying the association between myelodysplasia [a clonal disorder initiated by CHIP mutations] and several systemic inflammatory conditions [i.e. CAD, peripheral vascular disease (PVD), obesity, depression and COPD]. Methods: A cross-sectional analysis of a nationally-representative sample of inpatient hospitalizations in the United States between 2007 and 2015 [750,249 MDS-related hospitalizations, or 83,361 hospitalizations per year] was performed to identify co-occurring inflammatory diseases during hospitalizations in patients older than 35 years, in which MDS was documented. Given the inflammatory nature of the disease, subgroups were defined to investigate the prevalence of individual inflammatory domains (per 1,000 MDS-related hospitalizations) according to Revised-International Prognostic Score System [R-IPSS]. Subgroup analysis was performed for patients based on age (above and below 65 years), and race/ethnicity. Prevalence and confidence intervals [CI] were obtained for each inflammatory condition. "Relevant" inflammatory domains were considered statistically significant based on non-overlapping 95% CIs. Results: In examined admissions, prevalence for CAD in (Low-risk) LR- MDS age 65 was 12.2 vs 24.7, PVD 21.8 vs 60.2, [Fig 1 A and B] obesity 88.1 vs 51.7, major depression 14.6 vs 5.3, COPD 42.1 vs 70.7, p=0.0001 for all comparisons [Fig 1 B and C]. Conversely, prevalence for CAD in (High-risk) HR MDS age 65 was 9.1 vs 17.3, p=0.04; PVD 14.5 vs 43.2, p=0001; obesity 73.7 vs 42.2, p=0.003 major depression 5.1 vs 6.9, p=0.04 and COPD 23.0 vs 34.6, p=0.05. Differential prevalence expression for CAD was observed between non-Hispanic Whites (W) and Hispanics (H) [22 vs 28, p=0.02]. PVD was more prevalent, in both W vs H [64.6 and 52.2, p= 0.0002] and NH-Blacks/African Americans (AA) vs H [63.1 vs 52.2, p= 0.009]. Obesity was more prevalent among AA and H [64.1 and 62.9, respectively] than in W [51.9, p=0.009 for W vs AA and p=0.0002 for W vs H]. Similar expression for diabetes was observed between H vs W [404 vs 282, p

Description: Background In plasma cell neoplasms, the percentage of plasma cells in bone marrow (PPCBM) is important for diagnosis and assessment of the treatment. This quantification is performed using bone marrow multiparameter flow cytometry (FC), aspirate smears (BMA) and biopsy. Differences among the percentage of infiltration detected by these techniques have been reported, which can be related to a heterogeneous pattern of infiltration of multiple myeloma (MM) or sample quality. However, a simultaneous evaluation of these three techniques has not been reported nor their ability to detect bone marrow involvement with high or low infiltration, associated with different stages of this disease. Purpose The aim of this study was to compare the results of PPCBM obtained by FC, BMA, and biopsy with CD138 immunohistochemistry (BMB) in different stages of the disease with high and low infiltration, and the ability of these techniques to correctly classify the disease. Methods Pathological studies of patients referred to Hospital Fundación Santa Fe, Colombia were reviewed between January 2015 and June 2018. The selection of patients was based on both, a diagnosis of plasma cell neoplasms, classified according to the International Myeloma Working Group criteria and the simultaneous use of FC by FACSCanto II flow cytometer (Infinicyt 2.0 software program), wright-stained aspirate smears and biopsy with CD138 immunohistochemistry in the detection. Descriptive analysis was performed and PPCBM was expressed as the mean± standard error of the mean (SEM). The Kruskal-Wallis test was used to compare the mean of PPCBM among the three methods. Lineal regression and Spearman´s coefficient were used to correlate the variables. Statistical association was considered significant for p values

Description: Background: Acute myelogenous leukemia [AML] in elderly patients has a poor prognosis. Age is a unique adverse predictor. However, the higher incidence of complex karyotype, secondary AML, and other unfavorable European-Leukemia-Network -2017 [ELN-2017] features are common. Induction failure is frequent and associated with chemotherapy resistance. These factors highlight an urgent need for "novel" therapy development. In recent years, in vitro, anti-tumor activity of Selective Serotonin Reuptake Inhibitors [SSRIs], such as Sertraline, have been demonstrated. Increased apoptosis, autophagy activation, and favorable modulation of P-glycoprotein and multidrug-resistance-associated-proteins are proposed mechanisms of anti-tumor effect. In this study, our primary aim was to detect "early [day 14] blast reduction" among patients [pt] receiving adjuvant SSRIs in combination with induction therapy as compared to patients who do not receive SSRIs. Additionally, we evaluated overall survival [OS] and relapse free survival [RFS] patients with and without exposure to SSRIs. Methods: With prior IRB approval, 176 pt diagnosed with AML from 1995 to 2017 at Baylor College of Medicine institutions [Michael E. DeBakey VA Medical Center and Baylor St. Luke's Medical Center] were analyzed. We identified older (age〉65) pts who received or did not receive SSRI for at least 6 months prior to induction therapy. "Early blast reduction" was evaluated by bone marrow (BM) exam on day 14. OS and RFS were evaluated by the Kaplan Meier method using PRISM 5. Independent variables with potential effect on OS and RFS [Mann-Whitney P=

Description: Transcriptional silencing of tumor suppressor genes, associated with DNA methylation, is a common epigenetic event in leukemias and myelodisplastic syndromes. Much less is known about the specific methylation changes that occur in DCLC, FL and their normal counterpart BFH. Methylation of cyclin dependent kinase inhibitors is more common in high grade lymphomas and may be an important step in the progression and transformation of follicular lymphoma. We determined the methylation status of 7 tumor suppressor genes in 31 patients with B-cell malignancies. Seven patients with benign follicular hyperplasia were used as normal controls. The target genes chosen are potentially involved in B-cells malignancies and encoding proteins implicated in apoptosis regulation (death associated protein kinase, DAP-K), Jak/STAT3 signalling pathway (SHP1), hormonal response (RARb), DNA repair (O6-methilguanine-DNA methyltranferase, MGMT), cell cycle control (p14ARF and p15INK4b) and detoxification of environmental xenobiotics such as doxorubicin (glutathione S-transferase P1, GSTP1). Genomic DNA extracted from paraffin-embedded samples of thirty one B-cell malignancies (twenty six DLCL and five FL) were analyzed by methylation-specific polymerase chain reaction to determine promoter hypermethylation of DAP-k, SHP1, Rarβ, MGMT, p14, p15 and GSTP1. Samples were obtained mostly from lymph nodes; spleen, stomach, skin, and parathyroid gland biopsies were also included. Specimens were collected at diagnosis before specific therapy. Diagnosis was based on morphology and immunohistochemistry analysis. All cases were matched for age, sex and ethnic origin. DAP-k promoter methylation occurred with similar frequency in DLCL (100%), FL (100%) and BFH (86%). SHP1 was methylated in 75% of DLCL, all FL and the 7 patients with BFH. RARb was methylated in all DLCL and FL patients and 85% of the BFH. Sixteen (50%) DLCL, three (60%) FL and none BFH patients showed MGMT methylation. Promoter hypermethylation of p14 and p15 was detected in 11 (42%) and 13 (50%) DLCL, 2 (40%) and 3(60%) FL, 3(42%) and 5(71%) BFH patients respectively. Methylation of GSTP1 was absent in all samples. Inactivacion of DAP-K, SHP1 and Rarβ is present in B-cell malignancies, DLCL and FL, and BFH. Therefore, it may represent a physiologic event conferring a temporal survival advantage necessary for a BFH response. With our data methylation of Cyclin dependent kinase inhibitors such as p14 and p15 is not a differential pathogenic event in DLCL with respect to FL or BFH. Finally, the absence of GSTP1 methylation in DLCL and FL questions its relevance in B-cell neoplasia development.

Description: Background LR-MDS is a heterogeneous group of clonal marrow disorder associated with ineffective hematopoeisis and complex genomic etiology. For patients (pt) with refractory cytopenia phenotype (RC-P), transfusion and growth factor support, such as Erythropoietin Stimulating Agents (ESAs) and Granulocyte Colony Stimulating Factor (G-CSF), are treatment options. Response rates for ESA is about 30%, (and response potentiation can be achieved in about 35% of pt receiving concurrent G-CSF.However, ESA unresponsiveness is a common phenomenon and is associated with transfusion dependence, normal/high EPO levels, and  high IPSS score. Therefore, novel therapies are greatly needed. Biologically, LR-MDS is linked to deregulation of apoptosis and cytokine signaling pathways. Selective Serotonin Reuptake Inhibitors (SSRIs) can induce normalization of deranged cytokines such as IL6 and TNF-α in clinical depression. In animal model of arthritis, sertraline abrogates manifestation of autoimmune arthritis by reducing TNF α. Our group recently showed that significant improvement in overall survival (OS) can be achieved in low-risk MDS patients treated with SSRIs, such as sertraline, which is independent of concurrent MDS directed therapy. (Li, et al. ASH 2012 abstract # 3818) Here, we report a case of sequential reversal of transfusion and growth factor dependence phenotype in a pt with refractory anemia multi-lineage dysplasia LR- MDS. Methods A 72-year male with transfusion dependent refractory anemia (8 units RBC in 8 weeks) was evaluated in clinic. His bone marrow showed erythroid and megakaryocytic dysplasia consistent with RCMD by WHO 2008 classification. Cytogenetic study revealed 45;X-Y[4];46 XY[16]. R-IPSS=1.5 (Cytogenetic=0; blast [0%] =0; Hb=7g/dL=1.5; Platelets [135000] =0; ANC [1500] =0). EPO and ferritin levels were 449 IU/L and 1600 NG/ML, respectively. R-H-EPO was administered at 40000 IU subcutaneously (SQ) per week. In view of severe depression, pt initiated sertraline at 100 mg orally on day (D) 61 of treatment. Response after 12 weeks of ESA, sequential addition of G-CSF and sertraline, were assessed according to internal working group (IWG) 2006 criteria. Results After 3 months of standard weekly SQ ESA (D1-D92) (Fig.1), and given ESA refractoriness, G-CSF at 480 mcg SQ 5-times weekly was added (ESA + G-CSF schedule) (D92-D189).Transfusion independence was observed by D 161 of combined ESA+G-CSF(Fig.1). Progressive hemoglobin stabilization resulted in G-CSF dose reduction to twice a week from D189 –D 257 (Fig. 1). Sequential resolution of ESA dependence was observed from D257- D515.  Over the treatment period, the absolute increase in Hb level was 4.2 g/dL from baseline. Restoration of ESA erythroid response was observed by D93-210 after G-CSF and sertraline addition. (Table. 1) Sustained and improved Hb levels were achieved after 200 days of G-CSF discontinuation and ESA dose de-escalation while on sertraline treatment. Conclusions Reversal of transfusion dependence represents a critical step in treatment algorithm of LR-MDS pt presenting with refractory anemia. In this context, ferritin normalization has previously been recognized as independent prognostic factor for outcome in MDS. Our case suggests feasibility of restoration of ESA sensitivity with concurrent G-CSF+ sertraline, and evidence for sustained beneficial effect of sertraline while ESA de-escalation, which seems independent from G-CSF. The MDS disease modifying effect of sertraline in LR- MDS patient presenting with refractory anemia and experiencing ESA refractoriness should be evaluated in prospective trials. Disclosures: No relevant conflicts of interest to declare.

Description: An abnormal fibrinogen was demonstrated in the plasma of an eleven year old boy with thrombotic thrombocytopenic purpura during the acute disease and during one clinical relapse nine months later. The altered fibrinogen was antigenically similar to normal fibrinogen but migrated more rapidly toward the cathode. The abnormal fibrinogen was incompletely precipitated by ammonium sulfate or heat, but was clottable by thrombin. Thrombotic thrombocytopenic purpura may be associated with incomplete in vivo defibrination and a circulating partially degraded fibrinogen. A patient with this syndrome is alive and well forty months after treatment with 200 mg. of prednisone daily.

Description: Background MDS encompasses a heterogeneous group of clonal marrow disorders resulting in various degree of ineffective hematopoiesis and risk of Acute Myelogenous (AML) transformation. Intuitively, the original IPSS (4-categories) lacked predictive power to dissect subgroups with more aggressive biological behavior suitable for MDS disease modifying strategies. The new coalesced R-IPPS discriminates biological subgroups and enhances predictive power based on redefined cytogenetic [5-categories-very good: -Y, del(11q); Good: e.g., normal karyotype, del(5q), del (20q); intermediate: e.g., +8,+19, del(7q); poor: e.g., -7 inv 3/del(3q), complex 3 abnormalities (abn); very poor: complex 〉 3 abn], depth of cytopenias and revised blast count subcategories at disease initiation, therefore allows more precise risk adapted intervention. Here, we aimed at validating the impact of cytogenetic subcategories on survival and initiated exploration of applicability of R-IPSS in our cohort of veterans diagnosed with MDS. This strategy allowed gaining insight into intrinsic disease characteristics and survival of our population. Methods From 2000-2012, 124 patients (pts) with confirmed diagnosis MDS were identified from the Michael E. Medical Center Cancer Registry. Long rank test was used to compare median Overall Survival (OS) in all generated cytogenetic and R-IPSS subgroups. Given the known effect of patient age on survival, all scored pts had survival age- adjusted using previously described formula (Greenberg. Blood. 2012). Results  Among pts studied, median age was 72 years (range, 53-91). With a median survival for the all cohort of MDS pts of 17.6 months (mo), the 3-years overall survival (OS) was 55%. In our cohort, cytogenetic classification revealed discriminative parameter from variables contained in R-IPSS with OS for very good of 32 mo (N= 10 [9.4%]), good of 26.2 mo (N=64 [59.8 %]), intermediate of 16.8 mo  (N=10 [12.8%]), poor of 12.1 mo (N=14 [16.7%]) and very poor of 4.2 mo (N=9 [7%])  (P=0.5; P=0.11; P= 0.13,P =0.08; P=0.02, respectively) (Fig.1). R-IPSS was calculated as reported. Median OS for patients in low, very low, intermediate, high and very high-risk categories were 34, 35.5, 14.5, 15, 7.8 mo, respectively (Fig.2). Age adjusted median survival estimation allowed more robust discrimination of survival with median survival of 35.5 months (mo) (P=0.8; HR=1), 18.2 mo (P=0.49; HR=1.9), 15 mo (P=0.008; HR=2.1) and 8.5mo (P=0.00; HR=4.1) for low, intermediate, high and very high-risk subgroups (Fig.3). No statistical significance difference in survival was observed between very low and low risk categories. Conclusions Our results validate the predictive value of the newly developed cytogenetic risk stratification groups contained in R-IPSS. For cytogenetic risks, clinical trends were observed across very low, low, intermediate and poor risk with significant different survival seen between poor and very poor cytogenetic groups. When taking in consideration all variables included in R-IPSS, a more precise discrimination of biological subgroups was observed after cohort age-adjustment. Larger pts samples are needed to refine difference in survival between very low and low categories. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2121 Background: The use of asparaginase (ASP) in treatment regimens for adult acute lymphoblastic leukemia (ALL) patients (pts) is a challenge due to its toxicity profile. Adverse events associated with ASP use include hypersensitivity reactions, coagulation disorders, hepatotoxicity, pancreatitis and hyperglycemia. Life-threatening complications compromise completion of treatment, and even pt suitability for bone marrow transplantation if required. We report our single institution experience with ASP acute toxicities in adult pts diagnosed with ALL. Methods: From 1993–2007, 135 pts (median age 38 years; range 18–76) were treated with ASP as part of their ALL directed regimen, of which 84 (62%) and 51 (38%) received L and Peg-ASP, respectively. Approximately 794 and 51 doses of L- and Peg-ASP were given, respectively. Acute toxicities were graded according to CTCAE version 3.0 at pre, peak (7d) and post (14d) ASP treatment. Grade 1 (G1) through grade 4 (G4) toxicities were evaluated during both induction and intensification. For each patient, the number and proportion of all toxicities (G1-G4) were calculated. Results: There was a higher frequency of toxicities with L- compared to Peg-ASP after controlling for age and gender. The average proportion of G2-G4 toxicities was 25% for L-ASP pts compared to 13% for Peg-ASP (p 〈 0.001). G3 toxicities were seen in 78% (65/82) of pts receiving L-ASP and 50% (26/52) with Peg-ASP (p=0.02), and G4 toxicities were seen in 23% (19/83) and 8% (4/52) of L-ASP and Peg-ASP pts, respectively (p=0.07). Additionally, a greater proportion of L-ASP vs Peg-ASP pts (42% v 3%) had elevation of liver function test (ALT) at the post-induction time point (p 〈 0.001). Similar results were seen for AST, Alk phos and glucose levels (all p values 〈 0.05). Decreased fibrinogen levels were also seen more frequently in patients receiving L-ASP (57%) vs Peg-ASP (30%) patients (NS). The proportion of laboratory measurements that were G2 toxicity or higher increased with age for L-ASP (0.2% per year, p=0.05) but not Peg-ASP pts (0.06% per year, p=0.55). However, when adjusting for dose agent, the proportion of G2-G4 toxicities was 0.14% higher with each increasing year of age (p=0.05). Furthermore, males also had a greater proportion of G2-G4 toxicities since there was a 4.4% lower rate of toxicities reported for females as compared to males (p=0.05). Notably, higher grade toxicities were seen in pts with increasing age with either L- or Peg-ASP. The median ages for L-ASP pts with a G2, G3 and G4 were 40.5, 41 and 55 years. The median age for those pts who received L-ASP and experienced a G4 toxicity vs those pts who received L and had no G4 toxicities was 55 years old vs 39 (p=0.018). The median ages for Peg-ASP pts with G2, G3, and G4 toxicities were 32, 34 and 57 years respectively. With both L- and Peg-ASP groups combined, the median age for those pts having a G3 toxicity vs those pts without any G3 toxicities was 40 vs 32 years (p=0.012) and for G4 toxicity was 55 vs 36 years (p=0.001). Conclusions: In adult ALL pts who receive ASP, therapy with L-ASP was associated with (1) increased liver function tests including ALT, AST and alk phos as well as a trend for lower fibrinogen levels post induction therapy and (2) a higher likelihood of G4 toxicities as compared to therapy with Peg-ASP. Regardless of the dosing agent, higher grade toxicities were seen in pts with increasing age, although this was most notable in patients who received L-ASP. Male pts receiving ASP were also more likely to suffer from G2 or higher toxicities as compared to female pts. The use of either L- or Peg ASP should be closely monitored in adult patients with ALL and if toxicities arise, it is likely that the older patients will suffer from higher grade toxicities. Disclosures: No relevant conflicts of interest to declare.