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INTRODUCTION Lymphomas represent the fourth most frequent type of cancer, 90% of them arising from B cell lymphocytes. Despite their high prevalence, around 40% remain incurable because of refractoriness to current chemoimmunotherapy or disease relapse after obtaining response (Li et al., 2018; Meng et al., 2020). The cell of origin is a B lymphocyte with a unique B cell receptor (BCR). The BCR is an immunoglobulin composed of two heavy chains (IgH) and two light chains (IgL) whose genes have multiple coding segments that through rearrangement first and further somatic hypermutation in the germinal center, generate a unique sequence that could be used to monitor the treatment response (Seifert et al., 2019; Wang et al., 2020). This project studies the use of next-generation sequencing (NGS) to characterize and monitor such IgH clonality. The use of liquid biopsy samples would provide a minimally invasive method to identify refractory or relapse-risk patients since all of them will have residual tumor cells after treatment. METHODS The sample size of the study was 53 patients with several types of B-cell lymphomas. The IgH gene of the tumor clone was characterized from DNA of tumor samples at diagnosis by NGS and Sanger. The monitoring of this clone was studied by NGS from DNA and circulating tumor nucleic acids (ctNAs) during and after receiving treatment and at different times after clinical response was stablished (CR or PR). Relapse samples were analyzed by NGS and Sanger. RESULTS Characterization of the tumor clone IgH rearrangement is achieved in 45 of the 53 patients with B-cell lymphoma included in the study. As shown in Figure 1, after the two different amplification PCRs results are similar. In contrast, after sequencing the results obtained by Sanger and NGS are very different. In NGS, thanks to the massive amplification prior to sequencing, it is identify the tumor clone in approximately 80% of the samples. It is shown that the effectiveness in characterization is dependent on the origin of the DNA sample, with fresh material samples being the optimal (Figure 1). In monitoring, samples of different origin are used as shown in Figure 2. About 50% of these samples are plasma ctNAs whose average efficiency in the detection of IgH gene rearrangement is 73.3%, with a clear positive correlation between the sensitivity and the toal volume of plasma processed more starting plasma used (2 mL efficiency of 84.09%). Monitoring makes it possible to classify patients into three different groups (Figure 3): patients with complete remission, patients refractory to the different lines of treatment and patients with apparent complete response and subsequent relapse. In patients with complete response, the tumor clone decreases during treatment and at the end of the line it is no longer detectable, nor in subsequent follow-up samples. With respect to refractory patients, it is observed that the tumor clone remains present despite subsequent lines of treatment. Finally, in patients achieving CR with subsequent relapse, the clone can be detected in a small percentage at the end of the treatment schedule and remains present until relapse. A section of patients under treatment is also shown (Figure 3) to demonstrate the application of the study to clinical practice. Two patients with apparent complete response, one of them in complete remission and the other with a high risk of relapse, requiring a more exhaustive follow-up. The monitoring results obtained by flow cytometry are shown being these, in general, concordant. In some cases NGS shows greater sensitivity. CONCLUSION The use of NGS and liquid biopsy samples provides a minimally invasive method to monitor the IgH gene rearrangement of the tumor clone of patients with B-cell lymphomas. In our experience,, patients in remission can be clearly differentiated from those who are refractory or at risk of relapse. facilitating their treatment strategy and clinical decision making. Figure 1 Figure 1. Disclosures Ferrer Lores: Janssen: Membership on an entity's Board of Directors or advisory committees. Terol: BMS: Consultancy; Hospital Clinico Valencia: Current Employment; Roche: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel.

Introduction Pediatric inspired regimens can achieve good outcomes in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) by delivering intense non-myelosuppressive chemotherapy and are considered standard. Experience with the implementation of these regimens outside of academic centers in high-income countries is limited. Furthermore, Mexican patients (with "hispanic ethnicity") have increased risk for relapse and treatment related complications. Objectives Primary objective: to determine 2-year overall survival (OS) and event-free survival (EFS). Secondary objectives: to determine the impacts of treatment abandonment and measurable residual disease (MRD) on outcomes, and to compare treatment costs with a widely used standard regimen in the United States. Patients and Methods Consecutive patients 16-45 years diagnosed with Ph-negative B-cell acute lymphoblastic leukemia after 2016 were included. The salient features of our modified-BFM regimen include the use mitoxantrone, E. coli L-asparaginase, without systemic cytarabine or high dose methotrexate designed to be delivered entirely in an outpatient basis for maximum affordability (Table 1), given that we treat an uninsured population that must cover their own treatment costs out of pocket. Genetic risk assessment was limited to BCR/ABL. Thereafter, relapse risk assessment was based exclusively on "next generation" flow cytometry measurable residual disease (MRD) after consolidation, with a planned allogeneic transplant for MRD-positive patients (≥0.001%). Treatment abandonment was defined as a missed ≥14-day period during intensive treatment or ≥1 month during maintenance. Statistical analysis was performed as intent-to-treat. Lastly, drugs included in our protocol were compared to those of CALGB 10403 with current local pricing in USD. Results Ninety-one AYAs have been treated, 47 women and 44 men, with a median age of 21 years (range, 15-45), mostly with a good functional capacity and no comorbidities (ECOG≤2: 92.1%; HCT-Ci 0-1: 97.8%); 43.8% of patients had ≥30x10 9/L white blood cells at diagnosis and 31.7% had grade ≥1 obesity. Notable grade ≥3 adverse events during induction were infections/neutropenic fever (35.6%),hepatotoxicity (11%) and thrombosis/bleeding (8.1%) with 44.3% eventually requiring hospitalization. Induction related mortality was 11%. Only n=3 were refractory to induction and the remainder assessed achieved complete remission (n=63; 95.5%) with a median follow-up of 15 months (range, 0.9-50.1). N=29 received induction and consolidation entirely on an outpatient basis, ulterior hospitalizations during therapy were rare. Treatment abandonment was common (n=24; 26.4%) usually during induction (n=8; 32%) or consolidation (n=12; 48%) and mostly related to unaffordability. For the same reason, transfers to social security healthcare systems were also frequent (n=19; 20.9%). Most patients assessed were MRD negative (n=38; 74.5%) Early relapse incidence was 32.9%; 44.4% in MRD-positive and 27.5% in MRD-negative patients (p=0.43). OS at 24 months was 61.5% (95% CI 47-73%) and EFS 49.8% (95% CI 37-62%) with excellent outcomes for MRD-negative patients (Figure 1, Panels A and B). Treatment abandonment and MRD positivity were the only independent predictors of mortality in a multivariate analysis (HR 7.8 [95% CI 2.8-21.9] and HR 4.5 [95% CI 1.4-14], respectively). Lastly, the total cumulative price for medications included in our regimen was calculated at $16,750 vs. $36,061 USD in CALGB 10403, representing a cost reduction of 53.5%. Conclusions The treatment of Hispanic ALL patients with our regimen has shown promising outcomes at a reduced cost for patients. Genetic risk assessment, induction mortality, treatment abandonment and lack of access to novel therapies for MRD positive patients remain the main barriers for improving outcomes further. Figure 1 Figure 1. Disclosures Gomez-De Leon: Novartis: Honoraria; ASH: Research Funding; Sanofi: Honoraria; Abbvie: Honoraria. González López: JANSSEN: Honoraria; AMGEN: Honoraria. Gomez-Almaguer: Roche: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau.

Introduction: Among the genetic lesions described in chronic lymphocytic leukemia (CLL), TP53 and IGHV mutational status are well-established prognostic biomarkers. While mutations resulting in dysregulation of TP53 are associated with chemo-resistance, mutated IGHV (IGHV-M) identifies a good prognosis and unmutated (IGHV-UM) is associated with an aggressive clinical outcome. Thus, molecular assessment of TP53 and IGHV mutational status is recommended to make treatment decisions. Moreover, 30% of CLL patients have a highly homologous complementarity-determining region 3 (CDR3), allowing their classification in subsets based on the stereotypical B-cell receptor immunoglobulins (BcR IG), which have been associated with different clinical features and outcomes. This study aimed to assess the mutational status of TP53 and IGHV and the frequency of stereotypical BcR IG subsets, including CLL#2 and CLL#4 associated with poor and good prognosis, respectively, in a large series of CLL patients in Spain. Methods: Observational, retrospective, cross-sectional, multicentric study of data from the RED53 project, a collaborative network between the Spanish Group of CLL (GELLC) and Janssen for the characterization of TP53 and IGVH mutational status in naïve CLL candidate patients to receive treatment. Blood samples from 225 institutions were collected between May 2016 and March 2021. Included patients had confirmed diagnosis of CLL and required first-line treatment. Basic demographic variables, leukocyte and lymphocyte counts, and the number of clonal CD5 +/CD19 + lymphocytes were recorded at sample extraction. Clonotypic IGHV-IGHD-IGHJ gene rearrangements and exons 4 to 10 of TP53 were amplified by PCR and sequenced (Sanger). Four analytical reference centers qualified by the European Initiative for CLL (ERIC) determined the mutational status following the ERIC guidelines. Results: A total of 1097 samples from patients with a median (range) age of 70.0 (27-97) years were analyzed. At sample extraction, patients had a median (range) of 54.5 (2-516) x10 9 leukocytes/mL and 46.1 (0-8810) x10 9 lymphocytes/mL, of which a median (range) of 80.0 (1-100) % (n=754) were clonal CD5 +/CD19 + lymphocytes. The most frequent indications for treatment initiation were progressive/tumoral adenopathy (n=525, 50.4%), progressive lymphocytosis (n=429, 41.2%), cytopenia (n=369, 35.4%), and systemic constitutional symptoms (n=252, 24.2%). Median (IQR) age was 63.0 (55.0, 71.0) years at diagnosis and 70.0 (62.0, 77.0) years at treatment onset. Median (range) time from diagnosis to treatment was 2.7 (0.6-6.1) years. Among 1097 patients, 100 (9.2%) had TP53 mutations with 103 variants, of which only 3 (3.0%) had 2 mutations. Of the 103 mutations, 91 (88.3%), 9 (8.7%), and 3 (2.9%) were pathogenic, likely pathogenic, and of uncertain significance, respectively. Fig. 1 shows mutation localization and type. IGHV was UM in 58% (471/812) and M in 33.1% (269/812) of patients, and unknown/undetermined in 1.8% (15/812), non-productive in 3.2% (26/812), and borderline in 3.8% (31/812) of patients. IGHV rearrangements were undetected in 25.6% (279/1091) of patients and 65.7% (717/1091), 8.5% (93/1091), and 0.2% (2/1091) had 1, 2, and 3 rearrangements, respectively . Of the 30 patients with IGHV3-21 rearrangements, 18 had available data, of which all had CLL#2 subset and, of the 15 patients with IGHV-M, 5 (33.3%) had CLL#2. Minor subsets were found in 7 (46.7%) and 17 (33.3%) of IGHV-M and UM, respectively. The most frequent stereotyped BcR IG subsets were CLL#2, CLL#1, and CLL#6, in 24.3% (18/74), 23% (17/74), and 10.8% (8/74) of patients, respectively. Among the 60 patients with mutated TP53 and IGHV mutational study available, 66.7% (40/60) had IGHV-UM. Conclusions: In our real-world experience, results regarding TP53 M and IGHV UM (9.2% and 58.0% of patients, respectively) are similar to those reported in previous series of patients requiring first-line treatment, with a slightly higher predominance of IGHV-UM over IGHV-M cases. Subset CLL#2 was the most frequently identified, whereas the frequency of CLL#6 was higher than that reported before. Considering the difficulties associated with the analysis of TP53 and IGHV mutational status of most laboratories diagnosing CLL, the RED53 network allows access to these determinations to naïve CLL patients with active disease by a simple, fast, and standardized method. Figure 1 Figure 1. Disclosures Terol: Roche: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; BMS: Consultancy; Hospital Clinico Valencia: Current Employment. Ferrer Lores: Janssen: Membership on an entity's Board of Directors or advisory committees. Bosch: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; TAKEDA: Membership on an entity's Board of Directors or advisory committees, Other: Travel. Gonzalez Diaz: Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures. Crespo: Janssen: Consultancy; Astra Zeneca: Research Funding; Roche/Genentech: Research Funding. Alcoceba: Janssen: Consultancy. Esteve: Janssen: Current Employment. Loriente: Janssen: Current Employment. Villanueva: Janssen: Current Employment.

Introduction: Trauma-induced coagulopathy (TIC) is a multifactorial condition secondary to severe trauma. In TIC, early fibrinogen (FI) replacement and low dose of recombinant activated factor VII (rFVIIa) may positively impact outcome. Factor XIII (FXIII), on the other hand, may stimulate in vitro clot formation and clot stability. We hypothesized that combination of FI, rFVIIa and FXIII might normalize clot formation more effectively than the isolated use of each concentrate in a model of TIC. Aim: Evaluation of the procoagulant effect of isolated or combined use of FI, rFVIIa and FXIII in a model of TIC. Methods: TIC in vitro model was obtained by dilution of whole blood from seven healthy controls with isotonic saline (NaCl 0.9%) (2:3 whole blood:saline ratio). FI, rFVIIa and FXIII were spiked in combination or alone until obtaining final levels of 2 g/L, 1 μg/mL and 100 IU/dL respectively. Procoagulant effects of the different concentrates or their mixtures were evaluated by Rotational Thromboelastometry (ROTEM®, Werfen) triggered using starTEM® (calcium chloride 0,2 M) and exTEM® reagent (source of tissue factor) diluted with saline up to 1:100.000 (final dilution) for a better evaluation of both the extrinsic and intrinsic pathways of coagulation. The values of clotting time (CT: time until 2 mm of amplitude, in seconds), amplitude (parameter proportional to the clot strength) at 5 minutes (A5, in mm) and clot formation time (CFT: time from CT to 20 mm of amplitude, in seconds) were evaluated. Statistical analysis of differences was performed by One-Way ANOVA test assuming no paring of data and using the Holm-Sidak's correction for multiple comparisons with a family-wise significance and confidence level of 0.01. Statistical significance was set at p< 0.05. Results/Discussion: Data are summarized in Table I and Figure 1. CT needed the combination of two of more concentrates to reach the normal range suggesting that the administration of FI alone in TIC may not be enough to restore the patients' hemostatic potential. In regard to the clot strength evaluated by A5, the addition of FXIII or rFVIIa alone or in combination did not improve the value of A5 that was only normalized by the addition of FI. This effect of FI was increased in the presence of FXIII or rFVIIa which indicated that normal levels of FI might be required for rFVIIa or FXIII to be effective emphasising the possible benefit of the combinatory therapy. Like observed in A5, the velocity of clot formation evaluated by the CFT was normalised only by the addition of FI. However, the combination of FI plus FXIII + rFVIIa had a stronger effect on CFT compared with the combination of FI + FXIII or FI + rFVIIa, indicating that the improvement of thrombin generation due to rFVIIa plus an increment of fibrin formation and net stabilization through the contribution of higher levels of FI and FXIII respectively, might provide a beneficial synergistic procoagulant effect in TIC. Conclusion: The use of FI in TIC may contribute to increase the patient's hemostatic potential but might not be enough. Combinatory therapies based on the administration of FI, rFVIIa and FXIII might be of better benefit in this setting. Ex-vivo studies using blood of patients with stablished TIC might bring new insights on the possible advantages of this combinatory therapy to design more effective protocols to treat this frequent and life-threatening acquired condition. Disclosures Canales: Sandoz: Honoraria; iQone: Honoraria; Janssen: Speakers Bureau; Janssen: Honoraria; Roche: Speakers Bureau; Karyopharm: Honoraria; Sandoz: Speakers Bureau; Novartis: Honoraria; Takeda: Speakers Bureau; Roche: Honoraria; Sandoz: Honoraria; Janssen: Speakers Bureau; Roche: Speakers Bureau; Sandoz: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Honoraria; Karyopharm: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Roche: Honoraria; Gilead: Honoraria. Butta:NovoNordisk: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; SOBI: Speakers Bureau; Pfizer: Speakers Bureau; ROCHE: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Grifols: Research Funding. Alvarez Román:NovoNordisk,: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; SOBI,: Consultancy, Research Funding, Speakers Bureau; Pfizer,: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy; Grifols: Research Funding. Jiménez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria.

Introduction: Anemia affects a third of the world's population with the heaviest burden borne by women and children. Anemia leads to preventable impaired development in children, as well as high morbidity and early mortality among sufferers. Inherited hemoglobin (Hb) disorders, such as sickle cell disease (SCD), are associated with chronic hemolytic anemia causing high morbidity and mortality. Anemia and SCD are inherently associated and are both prevalent in the same regions of the world including sub-Saharan Africa, India, and south-east Asia. Anemia and SCD-related complications can be mitigated by screening, early diagnosis followed by timely intervention. Anemia treatment depends on the accurate characterization of the cause, such as inherited Hb disorders. Meanwhile, Hb disorders or SCD treatments, such as hydroxyurea therapy, requires close monitoring of blood Hb level and the patient's anemia status over time. As a result, it is crucially important to perform integrated detection and monitoring of blood Hb level, anemia status, and Hb variants, especially in areas where anemia and inherited Hb disorders are the most prevalent. Blood Hb level (in g/dL) is used as the main indicator of anemia, while the presence of Hb variants (e.g., sickle Hb or HbS) in blood is the primary indicator of an inherited disorder. The current clinical standards for anemia testing and Hb variant identification are complete blood count (CBC) and High-Performance Liquid Chromatography (HPLC), respectively. State-of-the-art laboratory infrastructure and trained personnel are required for these laboratory tests. However, these resources are typically scarce in low- and middle-income countries, where anemia and Hb disorders are the most prevalent. As a result, there is a dire need for high accuracy portable point-of-care (POC) devices to perform integrated anemia and Hb variant tests with affordable cost and high throughput. Methods: In 2019, the World Health Organization (WHO) listed Hb electrophoresis as an essential in vitro diagnostic (IVD) technology for diagnosing SCD and sickle cell trait. We have leveraged the common Hb electrophoresis method and developed a POC microchip electrophoresis test, Hemoglobin Variant/Anemia (HbVA). This technology is being commercialized under the product name "Gazelle" by Hemex Health Inc. for Hb variant identification with integrated anemia detection (Fig. 1A&B). We hypothesized that computer vision and deep learning will enhance the accuracy and reproducibility of blood Hb level prediction and anemia detection in cellulose acetate based Hb electrophoresis, which is a clinical standard test for Hb variant screening and diagnosis worldwide (Fig. 1C). To test this hypothesis, we integrated, for the first time, a new, computer vision and artificial neural network (ANN) based deep learning imaging and data analysis algorithm, to Hb electrophoresis. Here, we show the feasibility of this new, computer vision and deep learning enabled diagnostic approach via testing of 46 subjects, including individuals with anemia and homozygous (HbSS) or heterozygous (HbSC or Sβ-thalassemia) SCD. Results and Discussion: HbVA computer vision tracked the electrophoresis process real-time and the deep learning neural network algorithm determined Hb levels which demonstrated significant correlation with a Pearson Correlation Coefficient of 0.95 compared to the results of reference standard CBC (Fig.1D). Furthermore, HbVA demonstrated high reproducibly with a mean absolute error of 0.55 g/dL and a bias of -0.10 g/dL (95% limits of agreement: 1.5 g/dL) according to Bland-Altman analysis (Fig. 1E). Anemia determination was achieved with 100% sensitivity and 92.3% specificity with a receiver operating characteristic area under the curve (AUC) of 0.99 (Fig. 1F). Within the same test, subjects with SCD were identified with 100% sensitivity and specificity (Fig. 1G). Overall, the results suggested that computer vision and deep learning methods can be used to extract new information from Hb electrophoresis, enabling, for the first time, reproducible, accurate, and integrated blood Hb level prediction, anemia detection, and Hb variant identification in a single affordable test at the POC. Disclosures An: Hemex Health, Inc.: Patents & Royalties. Hasan:Hemex Health, Inc.: Patents & Royalties. Ahuja:Genentech: Consultancy; Sanofi-Genzyme: Consultancy; XaTec Inc.: Consultancy; XaTec Inc.: Research Funding; XaTec Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Genentech: Honoraria; Sanofi-Genzyme: Honoraria. Little:GBT: Research Funding; Bluebird Bio: Research Funding; BioChip Labs: Patents & Royalties: SCD Biochip (patent, no royalties); Hemex Health, Inc.: Patents & Royalties: Microfluidic electropheresis (patent, no royalties); NHLBI: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees. Gurkan:Hemex Health, Inc.: Consultancy, Current Employment, Patents & Royalties, Research Funding; BioChip Labs: Patents & Royalties; Xatek Inc.: Patents & Royalties; Dx Now Inc.: Patents & Royalties.

Introduction Immune-mediated hematologic disorders are relatively rare but potentially life-threatening immune-related adverse events (irAE) with immune checkpoint inhibitor (ICI) therapy (Shiuan, Beckermann et al 2017). The management strategy often relies on systemic corticosteroids and other immunosuppressant agents in steroid-refractory cases (Brahmer, Lacchetti et al 2018). We hereby describe our institution's experience in diagnosing and managing immune-related hematologic adverse events (ir-h-AE). Methods We retrospectively searched the electronic health record for all ir-h-AE diagnosed by treating providers and confirmed by study authors between 2015 and 2020. The search included patients on ICI and the following conditions: immune-related neutropenia (IRN), autoimmune hemolytic anemia (AIHA), cold agglutinin disease (CAD), immune thrombocytopenia (ITP), immune-related pancytopenia, aplastic anemia (AA), and pure red cell aplasia (PRCA). For AIHA, PRCA, and CAD, partial response (PR) was defined as hemoglobin greater than 10 g/dL but < 12 g/dL and 2 g/dL above the nadir without blood product transfusion. Complete response (CR) was defined as hemoglobin of ≥ 12 g/dL and 2 g/dL above the nadir without blood product transfusion (Peñalver, Alvarez-Larrán et al. 2010). For ITP, CR was defined as platelet count ≥ 100 × 109/L and absence of bleeding. PR was defined as platelet count ≥ 30 × 109/L and ≥ two-fold increase from the baseline count and absence of bleeding (Gómez-Almaguer, Tarín-Arzaga et al. 2013). For IRN, CR was defined as absolute neutrophil count (ANC) ≥ 1500/ mm3 on 2 consecutive measurements separated by 7 days; PR was defined as ANC ≥ 500/ mm3 sustained over 7 days. JMP® 14.1 was used for data analysis. Results Seventeen patients were identified, 9 (52.9%) of whom were female (table 1). Median age was 68 years (range 26-78). The most common pre-existing malignancies were melanoma (6 patients, 35.3%), non-small cell lung cancer (4 patients, 23.5%), and gastrointestinal cancer (3 patients, 17.6%). The ir-h-AE included 7 patients (41.2%) with warm AIHA, 4 (23.5%) with ITP (1 had immune-related pancytopenia that resolved with ITP persisting), 3 (17.6%) with IRN, 1 with AA, 1 with CAD, and 1 with PRCA and mild ITP. All patients had received an ICI dose within 60 days of diagnosis (range 3-52 days, median 18 days). Only 1 patient had a concomitant chronic autoimmune disorder (antinuclear antibody-positive arthritis). Four patients (23.5%) were receiving chemotherapy. Sixteen patients (94.1%) required treatment and received corticosteroids. Eight out of 15 evaluable patients (53.3%) responded to corticosteroids only. Another 4 responders (26.7%) required additional therapies including intravenous immunoglobulins (IVIG) (4, 23.5%) and/or rituximab (4, 23.5%). Overall response rate was 71.4% for AIHA and 100% for IRN. ITP was likely underrepresented in our cohort, and the response rate of 66.7% is likely lower than the response rate in clinical practice. This could be related to the fact that many mild thrombocytopenia cases are not further evaluated in clinical practice. None of our patients died from the sequelae of an ir-h-AE. Two patients (11.8%) died within 30 days of ir-h-AE diagnosis (disseminated intravascular coagulation likely due to the underlying malignancy and sepsis from bacterial pneumonia). At the time of ir-h-AE diagnosis, the malignancy was showing evidence of response in 9 patients (52.9%), progression in 6 patients (35.3%), and stability in 2 patients (11.8%). ICI therapy was permanently discontinued in 9 patients (52.9%) and temporarily held in 6 patients (35.3%). Three of the 5 patients (60%), who were rechallenged with ICI therapy, had recurrence of the same ir-h-AE (AIHA) with adequate response to therapy. Non-hematologic irAE (7 patients, 41.2%) included 3 patients with hepatitis, 2 with thyroiditis, 2 with pneumonitis, 1 with colitis, and 1 with dermatitis. Conclusion Our clinical experience with ir-h-AE highlights the importance of exercising vigilance in assessing the hematologic parameters of patients receiving ICI therapy. While relatively rare, ir-h-AE may impact the clinical course of patients with cancer and their eligibility for therapies that have the potential of offering durable control of the underlying malignancy. ir-h-AE respond to classical therapies including corticosteroids, IVIG, and rituximab. Disclosures Block: Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Marker Therapeutics: Research Funding; Transgene: Research Funding; Immune Design: Research Funding. Kottschade:Bristol-Myers Squibb: Consultancy, Research Funding.

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in malignant hematology by clinicians and payers in the US. The level of scientific evidence in NCCN guidelines for malignant hematological conditions has not been recently investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common hematologic malignancies with regard to recommendations for staging, initial and salvage therapy, and surveillance. Methods: NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are: category I, high level of evidence such as randomized controlled trials with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. We compared our results with previously published results from 2011 guidelines. Results: Total recommendations increased by 16.6% from 1160 (2011) to 1353 (2020). Of the 1353 recommendations, Category 1, 2A, 2B and 3 EC were 5%, 91%, 4%, 1% while in 2011 they were 3%, 93%, 4% and 0% respectively. Recommendations with category 1 EC were found in all guidelines, except for Burkitt's Lymphoma. 6.3% of therapeutic recommendations were category 1 EC with the majority (56.4%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were Multiple Myeloma (12.4%), CLL/SLL (6.9%) and AML (5.6%). Between 2011 and 2020, the proportion of category I recommendations increased significantly only in Follicular lymphoma and CLL/SLL. No category 1 EC recommendations existed in staging or surveillance. Conclusion: Recommendations issued in the 2020 NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. Despite the major advances in hematology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in malignant hematological disorders which forms the platform for clinical practice guidelines. Figure Disclosures No relevant conflicts of interest to declare.