Leukemoid reaction in chronic myelomonocytic leukemia patients undergoing surgery: perioperative management recommendations

Key Points CMML patients comprise an elderly and frail patient population with comorbidities that often require surgical intervention. Postsurgical leukemoid reaction, a life-threatening complication in CMML patients, may be driven by molecular mechanisms.</jats:p

Phase I Study of Pracinostat in Combination with Gemtuzumab Ozogamicin (PraGO) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)

Background: Relapsed/Refractory AML (RR-AML) represents an area in urgent need for new treatments, particularly among patients ineligible for intensive chemotherapy. Newer options exist for AML with mutations involving IDH1, IDH2, or FLT3, but in AML without these mutations, only gemtuzumab ozogamicin (GO) is currently approved. GO is a calicheamicin-conjugated antibody directed against the CD33 antigen, commonly found on AML. Mechanistically, GO binds to the CD33 antigen on AML forming a complex which is internalized, resulting in intracellular delivery of calicheamicin, DNA double-strand breaks and cell death.GO recently received re-approval for patients with RR-AML on the basis of the Mylofrance-1 trial, which demonstrated a CR rate estimated at 26%. This clinical trial was designed to assess the safety of adding pracinostat, a histone deacetylase inhibitor (HDACi) to GO. Inhibition of histone deacetylases has been shown to induce an open chromatin structure and potentially restore transcription of critically silenced genes. In AML, single agent pracinostat has demonstrated potential anti-leukemic activity (Abaza et al. Cancer 2017). We hypothesize that, HDACi may mediate histone unwinding, a more open chromatin structure, and potentiate DNA-targeted delivery of calicheamicin within AML blasts. Further, pre-clinical data suggests HDAC inhibition could also increase CD33 expression in myeloid leukemia cells, thereby allowing for increased GO binding to AML blasts (ten Cate et al. Leukemia 2007). Previously, vorinostat, another HDACi, has been used in combination with GO and azacitidine in AML. While that trial reported limited efficacy, this trial will incorporate a fractionated GO dosing schedule, as well as the use of a more potent HDACi, both of which may improve efficacy. Study Design and Methods: This is a prospective, investigator-initiated, phase 1 clinical study that is aimed at determining the safety of pracinostat + GO (PraGO) combination in patients with R/R AML (ClinicalTrial.gov identifier NCT03848754). Secondary end points are to evaluate response rates, 6-month progression free survival (PFS) and overall survival (OS). Eligible patients are either aged ≥ 60 years with RR- AML to at least one line of therapy, or patients 18-59 years with RR-AML to at least two lines of intensive induction chemotherapy, or one line of therapy if deemed unsuitable for further intensive chemotherapy. Diagnosis of acute promyelocytic leukemia (APL), hematopoietic stem cell transplantation (HCT) within 60 days of enrollment, evidence of veno-occlusive disease (VOD) at any time post-transplant, or active graft versus host disease (GVHD) requiring systemic immunosuppressive therapy are major exclusion criteria. Patients will be enrolled into two potential dosing cohorts. Cohort 1 will receive pracinostat at 45mg orally, three times weekly for three weeks. GO will be administered at 3 mg/m2 on Days 1, 4, and 7. The first dose of GO will be administered two hours after the first pracinostat dose. Responding patients will subsequently receive maintenance with GO alone at 2 mg/m2 on Day 1. Up to 5 cycles of GO will be administered to responders. Cohort 2 will receive pracinostat at 60 mg orally, three times weekly for three weeks. GO administration will remain the same for induction. Responding patients in this cohort will be eligible for maintenance with pracinostat at 45 mg orally, three times weekly for three weeks. GO will still only be given D1 in each maintenance cycle. A standard 3+3 design will be utilized to determine escalation to Cohort 2. DLTs will be assessed during the 1st cycle only. The study schema is diagrammatically illustrated in figure 1. With the hypothesis that HDAC inhibition may lead to increased CD33 expression, RNA seq will be performed on blasts isolated on BM aspirate, pre- and post pracinostat treatment. Other potential antibody targets will also be assessed, including CD22 and CD38. To date, one patient has been enrolled. This 72 years old male with MPN/MF transformed to AML, refractory to CLAG (cladribine, cytarabine, G-CSF) induction. On study, he achieved a partial remission after 1st induction cycle (bone marrow blast from 20% --&gt; 6.4%), with normalization of counts albeit with very short follow up, no SAE or DLTs were observed. Figure 1 Disclosures Runaas: Agios: Honoraria; Blueprint Medicine: Honoraria. Michaelis:Novartis: Consultancy; TG Therapeutics: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; Macrogeneics: Research Funding; Pfizer: Equity Ownership, Research Funding; ASTEX: Research Funding; Bioline: Research Funding; BMS: Research Funding; Celgene: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Millenium: Research Funding; Janssen: Research Funding. Atallah:Helsinn: Consultancy; Novartis: Consultancy; Jazz: Consultancy; Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy. Abedin:Agios: Honoraria; Jazz Pharmaceuticals: Honoraria; Actinium Pharmaceuticals: Research Funding; Pfizer Inc: Research Funding; Helsinn Healthcare: Research Funding. </jats:sec

The Prognostic Significance of Blast Aberrancies By Flow Cytometry in Low/Int Risk MDS

Background: The myelodysplastic syndromes (MDS) represent heterogeneous disorders with varied clinical courses. The major prognostic tool in MDS is the IPSS-R, which helps estimate survival outcome and estimate risk for AML transformation. In low or intermediate risk pts, the IPSS-R has shortcomings; in these pts, the development of transfusion dependent anemia is the major disease associated complication, and this is not addressed by IPSS-R stratification. Previous studies have indicated that aberrancies detected by flow cytometry can risk stratify pts with MDS. The purpose of this study was to determine whether detection of neoplastic-specific blast aberrancies in pts diagnosed with low or intermediate risk MDS can identify pts at higher risk for transfusion dependent anemia after MDS diagnosis. Methods: We performed a retrospective chart review on MDS patients initially diagnosed at our institution between 1/2010 and 12/31/2017. Patients with low/intermediate risk by IPSS-R were identified. Flow cytometry findings on initial diagnostic BM biopsies performed at our institution only were reviewed. Flow cytometry (4- and 8-color) was performed on bone marrow aspirates for the following antigens: CD3, CD7, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD36, CD38, CD45, CD56, CD64, CD117, and HLA-DR using FACS Calibur or FACSCanto II flow cytometers. Myeloblasts were identified by cluster analysis, as previously described (Am J Clin Pathol. 2010 Nov; 134(5):749-61), and compared to 20 control cases. Blast aberrancies were defined as an immunophenotypic difference of &gt; ¼ log compared to the blasts in the controls. Neoplasia-specific blast aberrancies were defined as: expression of CD7, CD11b, CD15, and/or CD56 and/or under expression of CD38 and CD45. We estimated probability of transfusion dependent anemia using Kaplan Meier product limit method and compared survival curves using log-rank test. Analyses were performed using Stata v12.0. Results: A total of 63 patients were identified, with median age of 68 years (range 31-89 years). Median hemoglobin (Hg) at diagnosis was 9.8 (range 5.2-15.3). Cytogenetic risk categories were very good, good, intermediate and poor in 3%, 71% 16%, and 10% respectively. IPSS-R category was very low or low in 70% (44 pts), and intermediate in 30% (19 pts). The presence of blast aberrancies was similar in proportion among low risk patients (61%, n=27) compared to intermediate risk patients (68%, n=13). Overall, the presence of only one blast aberrancy, whether neoplasia-specific or not, did not significantly segregate patients at greater risk for transfusion dependence. However, the presence of 2 or more aberrancies statistically defined two populations. Those possessing 0-1 blast aberrancy did not reach a median time to transfusion dependence, whereas those possessing 2+ aberrancies had a median time to transfusion dependence of 1.2 years (p=0.02). Additionally, when looking at neoplasia-specific blast aberrancies, pts with 0-1 aberrancy had a median time to transfusion of 4.7 years, compared to 2+ aberrancies, at 0.8 years (p=0.02). Figure 1 illustrates this finding. Conclusion: The determination of blast aberrancies by flow at time of MDS diagnosis may provide prognostic information in low/intermediate risk MDS patient and could help predict risk for early red blood cell transfusion dependence. Upfront risk stratification would be valuable information to plan follow-up for these patients, as well as treatment decision making including early initiation of ESAs. Disclosures Michaelis: Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; BMS: Research Funding; Bioline: Research Funding; ASTEX: Research Funding; Janssen: Research Funding; Millenium: Research Funding; Macrogeneics: Research Funding; Pfizer: Equity Ownership, Research Funding; Incyte: Consultancy, Research Funding. Runaas:Agios: Honoraria; Blueprint Medicine: Honoraria. Atallah:Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy; Jazz: Consultancy; Novartis: Consultancy; Helsinn: Consultancy. Abedin:Actinium Pharmaceuticals: Research Funding; Pfizer Inc: Research Funding; Helsinn Healthcare: Research Funding; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria. </jats:sec

A Multisite Phase Ib Study of Pevonedistat, Azacitidine and Venetoclax (PAVE) for the Treatment of Subjects with Acute Myelogenous Leukemia (AML)

Background: Outcomes of patients with AML have remained poor despite the availability of cytotoxic chemotherapy, hypomethylating agents (HMAs) and targeted therapies. HMAs, such as azacitidine, in combination with Bcl-2 inhibitors like venetoclax have demonstrated response rates of 67% in newly diagnosed AML and 21% in relapsed/refractory (RR) AML (DiNardo et al. Blood 2019 and Am J Hematol 2018). While the combination of azacitidine and venetoclax is efficacious in AML, preclinical studies indicate potential mechanisms of drug resistance including overexpression of MCL-1, an anti-apoptotic protein (Konopleva et al. Cancer Cell. 2006). Pevonedistat is a first in class inhibitor of Nedd8 activating enzyme that has demonstrated activity against AML (Swords RT et al. Blood. 2010). Pevonedistat induces NOXA, a pro-apoptotic protein leading to neutralization of MCL-1 inducing apoptosis (Wang et al. Biochem Biophys Res Commun. 2017). Preclinical studies evaluating the combination of pevonedistat and venetoclax against AML cell lines have demonstrated synergistic effect (Knoor KL et al. Cell Death Differ. 2015). Hence, we hypothesize that the addition of pevonedistat to the combination of azacitidine and venetoclax would enhance the therapeutic efficacy by overcoming resistance to apoptosis. Study design and methods: This is an investigator-initiated phase Ib study evaluating the safety of pevonedistat, azacitidine and venetoclax. Patients aged 18 years or above with morphologically documented AML (de novo, secondary or therapy-related), ECOG performance status 0-2 and adequate organ function are eligible for the study. Major exclusion criteria are patients with isolated extramedullary relapse, hematopoietic cell transplantation (HCT) within 100 days of enrollment, active acute GVHD, veno-occlusive disease, acute promyelocytic leukemia, liver cirrhosis and severe liver impairment. While the dose escalation phase is available only for patients with RR-AML, the dose expansion phase can also include newly diagnosed AML patients who are ineligible for intensive induction. The study is planned to be conducted at Medical College of Wisconsin, Mayo Clinic and University of Pennsylvania. The primary endpoint is to determine the recommended phase 2 dose (RP2D) and toxicity profile of pevonedistat, azacitidine and venetoclax. The secondary endpoints include determination of response rates, duration of response, survival and pharmacokinetics. Exploratory endpoints include correlation of response rates with AML genomic profile, correlation of pretreatment levels of BCL2, BCLXL, MCL1, BAX or BAK with response, determination of changes in NOXA (PMAIP1) mRNA and protein expression pre-and post-pevonedistat treatment, evaluation of BH3 mimetic profiling on bone marrow samples by flow cytometry and assessing the sensitivity of leukemia and leukemic stem/progenitor cells to pevonedistat ex vivo. The study will follow 3+3 design with dose escalation (Arms A and B), de-escalation in case of dose limiting toxicity (DLT) (arms Z and Y) and dose expansion phase (figure 1). Patients will be entered sequentially to each dose level, starting with dose level 0. The DLT observation period for dose-escalation will be 1 cycle. The maximal tolerated dose (MTD) will be defined as the highest dose level at which none of the first 3 treated subjects, or no more than 1 of the first 6 treated subjects experiences a DLT. A minimum of 9 and a maximum of 24 patients will be needed for the dose escalation phase and 6 patients for the dose expansion phase. Response rate, duration of response and exploratory endpoints will be analyzed using descriptive statistics. Kaplan-Meier method will be used to determine survival. Disclosures Guru Murthy: Cardinal Health Inc.: Honoraria. Michaelis:Incyte: Consultancy, Research Funding; Pfizer: Equity Ownership, Research Funding; Novartis: Consultancy; Macrogeneics: Research Funding; Millenium: Research Funding; BMS: Research Funding; Celgene: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; TG Therapeutics: Consultancy, Research Funding; Janssen: Research Funding; ASTEX: Research Funding; Bioline: Research Funding. Abedin:Jazz Pharmaceuticals: Honoraria; Agios: Honoraria; Helsinn Healthcare: Research Funding; Pfizer Inc: Research Funding; Actinium Pharmaceuticals: Research Funding. Runaas:Agios: Honoraria; Blueprint Medicine: Honoraria. Atallah:Jazz: Consultancy; Novartis: Consultancy; Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy; Helsinn: Consultancy. </jats:sec

Reducing Venous Thrombosis with Antithrombin Supplementation in Patients Undergoing Treatment for ALL with Asparaginase Based Regimens

Abstract Introduction The dramatic improvement in outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) has led to the incorporation of asparaginase into adult treatment protocols. However, increased thrombosis rates have been subsequently observed. In an effort to reduce venous thromboembolism (VTE) rates in this high-risk population and minimize the morbidity and cost associated with each event, Froedtert &amp; the Medical College of Wisconsin implemented a practice of three-times weekly antithrombin (AT) activity monitoring with prophylactic AT supplementation (plasma derived antithrombin) for activity less than 50%. The type of AT used for supplementation was Thrombate III (human form) and dosing was weight-based (approximately 3000 units for patients &lt; 70 kg, 4000 units for patients 70-100 kg, and 5000 units for patients &gt; 100 kg) with a target AT activity level of 120%. Similarly, levels of fibrinogen were monitored three times weekly with cryoprecipitate supplementation provided for fibrinogen levels less than 100 if AT was also low. We retrospectively reviewed patient outcomes to determine impact of AT level monitoring with threshold-guided prophylactic AT infusions on VTE rates in patients undergoing asparaginase-based chemotherapy. Methods We conducted a single-center, retrospective, observational cohort study of ALL patients treated with asparaginase between 2009 and 2018. Patients were identified using our institution's hematological malignancy registry. The electronic medical record was reviewed for demographics, VTE events, AT activities, use of AT supplementation, and cryoprecipitate transfusion. Primary outcome was VTE events during treatment with asparaginase. We excluded catheter-related thrombosis from the outcomes. Secondary outcomes included: the number of patients receiving supplemental AT, the mean AT activity level (%) at the time of supplementation, number of asparaginase doses administered per patient, median number of days from asparaginase to VTE, median number of days from asparaginase administration to AT supplementation and the percentage of patients who received cryoprecipitate. The Fisher's exact test was used to compare categorical variables and Student's t-test compared continuous variables. Results A total of 65 patients were included: 20 patients were treated prior to protocol implementation (pre-intervention group), and 45 patients after implementation (post-intervention group). The median age of patients in the pre-intervention and post-intervention group was 35 and 38, respectively. The VTE rates were 50% (10 patients) in the pre-intervention group, and 25% (9 patients) in the post-intervention group (p = 0.02). The median number of days from asparaginase to VTE event was 15 in the pre-intervention group and 16 in the post intervention group. In the post-intervention group, 30 (46%) patients received AT and the mean AT activity level in supplemented patients was 46.7% (ranging from 32% to 64%). The median number of days from asparaginase administration to supplementation with AT concentrate was 8 days. A total of 28 patients (43%) received cryoprecipitate and the average fibrinogen level when patients were supplemented was 86.42 mg/dL. Fibrinogen levels were not monitored in the pre-intervention group. Conclusion Our results demonstrate that monitoring and replacing AT and fibrinogen in patients with ALL receiving asparaginase based regimens reduces the risk of VTE. Disclosures Atallah: Pfizer: Consultancy; Abbvie: Consultancy; Jazz: Consultancy; BMS: Consultancy; Novartis: Consultancy. </jats:sec

Comparison of Salvage Chemotherapy Regimens in Relapsed/Refractory Acute Myeloid Leukemia

Abstract Background Induction therapy for acute myeloid leukemia (AML) with a cytarabine-anthracycline regimen (7+3) is well-established; however, there is no standard salvage therapy for patients with relapsed/refractory AML (RR-AML). There is a paucity of data regarding outcomes with salvage regimens in RR-AML that include cladribine, cytarabine, and filgrastim with mitoxantrone (CLAG-M) or without mitoxantrone (CLAG), and mitoxantrone, etoposide, and cytarabine (MEC). We compared outcomes of patients receiving CLAG-M, CLAG or MEC as salvage therapy for RR-AML. Methods A multi-center retrospective study was conducted, including 146 adult RR-AML patients who underwent salvage therapy at the University of Wisconsin and Medical College of Wisconsin from 2009 to 2018. Demographic, clinical and pathologic factors were ascertained at the time of RR-AML diagnosis. The Center for International Blood and Marrow Transplant Research (CIBMTR) response criteria were used. Refractory AML was defined as failure to achieve remission after one or more courses of induction chemotherapy. Minimal residual disease (MRD)-negative was defined by the absence of leukemic cells by morphology and flow cytometry (&lt;0.01%). Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using chi-square and t-test, and logistic regression analyses were performed for baseline characteristics and response to salvage chemotherapy. Kaplan-Meier analyses, using the log-rank test, were conducted. Cox regression analyses were used to correlate factors with OS. Hazard ratios (HR) with 95% CI were obtained. Statistical significance was considered at P&lt;0.05. Results The study included 146 patients with relapsed (57.5%, n=84) or refractory (42.5%, n=62) AML who received CLAG-M (51%, n=74), MEC (39%, n=57) or CLAG (10%, n=15) salvage chemotherapy. Baseline characteristics were similar between the three groups (all P&gt;0.1). Median age was 60 years (range 22-77 years) and 59% patients were male. AML was classified according to WHO 2016 guidelines as AML with recurrent genetic abnormalities (23%), myelodysplasia (MDS)-related AML (25%), therapy-related AML (8%) and AML not otherwise specified (44%). Cytogenetics were good (5%), intermediate (60%) and poor (36%) with normal (41%), complex (25%), trisomy (8%) and monosomy 5 or 7 (5.5%) being common karyotypes. Among those who had molecular testing (n=119), NPM1 and FLT3-ITD were reported in 21% and 20% patients respectively. AML risk status was good (16%), intermediate (32%) and poor (52%), based on cytogenetic and molecular abnormalities as per ELN 2017 and NCCN 2018 guidelines. Extramedullary disease was present in 13% patients. Prior hematopoietic stem cell transplant (HSCT) was performed in 13% patients. Median lab values prior to salvage regimen were: hemoglobin 9.1 g/dL, platelets 49 K/uL, leukocytes 2.5 K/uL, LDH 231 U/L and bone marrow myeloblasts 28%. Overall response rate was 49% (CLAG-M 55%, n=41/74; MEC 44%, n=25/57, CLAG 40%, n=6/15) with complete remission (CR) rate of 46% (CLAG-M 54%, MEC 37%, CLAG 40%) [P=0.140]. Three percent patients (n=5; CLAG-M=1, MEC=4) had CR with incomplete hematologic recovery (CRi). MRD analysis was available for 83 patients and a trend was seen in MRD-negative CR rates favoring CLAG-M (44%) over MEC (25%) or CLAG (17%) [P=0.128]. Sixty-six patients (45%) received subsequent HSCT (CLAG-M 50%, n=37/74; MEC 44%, 25/57; CLAG 27%, n=4/15) [P=0.245]. At last follow-up, 34% patients were in CR (CLAG-M 42%, MEC 28%, CLAG 20%) [P=0.120]. Fifty (34%) patients were alive at last follow-up (CLAG-M 46%, MEC 23%, CLAG 20%) [P=0.010]. Median OS was 9.7 months (95% CI 6.8-12.6) that was significantly better with CLAG-M (13.3 months, 95% CI 2.4-24.3) compared to MEC (6.9 months, 95% CI 2.9-10.9) or CLAG (6.2 months, 95% CI 2.4-12.6) [P=0.025] Figure 1. In multivariate model adjusted for age, gender and refractory vs relapsed AML, MEC (HR 1.75, 95% CI 1.13-2.71, P=0.013) and CLAG (HR 1.97, 95% CI 1.02-3.79, P=0.043) regimens had worse OS compared to CLAG-M. After adjusting for age, gender, refractory vs relapsed AML and HSCT, CLAG-M remained independent predictor of better OS (HR 0.64, 95% CI 0.42-0.97, P=0.037). Conclusion CLAG-M compared to MEC or CLAG is associated with significantly better OS in RR-AML regardless of age, refractory vs relapsed AML and HSCT. Our findings support the use of CLAG-M as a preferred salvage regimen for RR-AML. Figure 1. Figure 1. Disclosures Atallah: Novartis: Consultancy; BMS: Consultancy; Jazz: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy. </jats:sec

40 Is the New 50: Reducing the Need for Platelet Transfusions Prior to Lumbar Puncture in Patients with Hematologic Malignancies

Abstract Introduction: Patients with hematologic malignancies frequently require lumbar punctures (LPs) for administration of intrathecal chemotherapy. With myelosuppressive chemotherapy, thrombocytopenia is common and patients often require platelet transfusions in order to reduce the risk of bleeding during invasive procedures. However, there is a dearth of evidence supporting a platelet threshold required for LPs. Guidelines from the American Association of Blood Banks recommend a minimum platelet count of 50 x 103/µL, but this is based largely on expert opinion. Platelet transfusion is associated with risk of transfusion reaction and alloimmunization, cost, and procedural delays. Given these risks, we instituted a reduction in platelet threshold to 40 x 103/µL for lumbar puncture. We retrospectively reviewed patient outcomes to assess the safety and efficacy of this approach. Methods: In November 2017, a platelet count threshold for LPs was introduced for adult oncology patients in both the inpatient and outpatient settings at Froedtert and the Medical College of Wisconsin. Previous guidelines recommended a platelet count of 50 x 103/µL in order to undergo a lumbar puncture. This threshold was decreased to 40 x 103/µL for oncology patients. Guidelines were agreed upon and implemented in all procedure settings: the inpatient procedure team, the outpatient procedure suite, and the radiology department (for fluoroscopy-guided lumbar puncture). Data regarding the pre-procedure platelet count, number of platelet transfusions given per procedure, CSF RBCs, and occurrence of post-procedure spinal hematomas were collected through the electronic medical record. Results: From November 1, 2016 to May 1, 2018 267 oncology patients underwent a lumbar puncture. Oncologic diagnosis was NHL, ALL, AML, solid malignancy, or other hematologic malignancy/disorder in 26%, 23%, 18%, 16%, and 17%, respectively. 42% of were female. A total of 845 LPs were performed under fluoroscopy, with ultrasound guidance, and by an experienced provider in 26%, 58%, and 16% of cases respectively. 534 LPs (63%) were performed with a platelet transfusion threshold of 50 x 103/µL (Plt≥50) and 311 LPs (37%) were performed with a platelet transfusion threshold of 40 x 103/µL (Plt≥40). The average pre-LP platelet count was 152.8 x 103/µL in the Plt≥50 group and 138.4 x 103/µL in the Plt≥40 group. 79 patients in the Plt≥50 group and 42 patients in the Plt≥40 group had a recorded platelet count between 40-49 x 103/µL within 24 hours prior to the procedure. After institution of the new guidelines, 40 LPs were performed with a platelet count &lt; 50 x 103/µL. The average number of units of platelets transfused per procedure significantly decreased from 0.58 to 0.39 after lowering the transfusion threshold (p &lt; 0.05). One lumbar epidural hematoma occurred post-intervention and one lumbar subarachnoid hematoma occurred pre-intervention, both in patients whose pre-procedure platelet counts were &gt; 100 x 103/µL. No traumatic hematomas were observed in patients whose pre-procedure platelet count was &lt; 50 x 103/µL. The incidence of traumatic taps (identified as CSF red blood cells &gt; 10/µL) was significantly higher in patients whose pre-procedure platelet count was &lt; 50 x 103/µL (64% vs. 46%, p &lt;0.05). Conclusion: Decreasing the LP platelet transfusion threshold from 50 x 103/µL to 40 x 103/µL significantly reduced platelet transfusions. This was not associated with an increased risk of complications. However, the incidence of traumatic taps was significantly higher in patients with a platelet count &lt; 50 x 103/µL. Given that the average cost of one unit of platelets is approximately 500 and 40 procedures were performed with a platelet count < 50 x 103/µL, decreasing the platelet transfusion threshold resulted in a cost savings of approximately 20,000 over the course of 6 months, not including administrative costs. Overall, this data suggests that lowering the platelet transfusion threshold for lumbar punctures to 40 x 103/µL is both safe and cost effective for oncology patients. Disclosures Atallah: Abbvie: Consultancy; Jazz: Consultancy; Novartis: Consultancy; BMS: Consultancy; Pfizer: Consultancy. </jats:sec