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Background: Chemoimmunotherapy using rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone (R-CHOP) has been the standard of care treatment of DLBCL for over 20 years. Despite its widespread usage, there is no accepted standard for the dose of prednisone in this setting which varies from fixed-dose (100 mg daily for 5 days) to different levels of BSA-adjusted dosage (ranging from 40-100 mg/m2 daily for 5 days). BSA-adjusted dosage results in high doses of prednisone administered to patients with increased body surface area which may lead to significant adverse events. We performed a systematic review and meta-analysis to determine if fixed-dose prednisone during R-CHOP therapy results in equivalent outcomes compared to BSA-adjusted dosing. Methods: A comprehensive search of several databases from each database's inception to April 29th, 2024, English language, was conducted. The databases included Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The search strategy was designed and conducted by an experienced librarian with input from the study's principal investigator. Controlled vocabulary supplemented with keywords was used to search for prospective clinical studies of R-CHOP for adult patients with untreated DLBCL. Search results were reviewed independently by 2 members of the study team for final inclusion. Discrepancies were adjudicated by a third member and reviewed by the senior author. Prednisone dosage and clinical outcomes were abstracted from the available public data. Meta-analysis was performed using the metafor package in R version 4.2.2 by applying a mixed-effects model to combine results from the multiple studies. The analysis was first conducted overall to determine the general effect, and then stratified by prednisone dose (fixed- vs. BSA-adjusted) to explore dose-dependent variations in outcomes. Results: Our search resulted in 2287 entries which were individually reviewed by the study team. A total of 30 studies with a combined sample size of 3573 treated patients fulfilled the inclusion criteria and were included in the final analysis set. Nineteen (63%) studies with a combined sample size of 1930 patients (median 155, range 12-399) used fixed-dose prednisone. Eleven (37%) studies with a combined sample size of 1643 patients (median 70, range 9-439) used BSA-adjusted dosing. Overall survival (OS) at 2 years data were available for 11 (37%) of the studies. Progression free survival (PFS) at 2 years data were available for 8 studies (27%). Overall response rate (ORR) and complete response rate (CRR) data were available for 16 (54%) and 14 (47%) of the included studies, respectively. OS at 2 years for all studies was 84% (SD 78%-91%) and did not differ between fixed-dose (88%, SD 79%-97%) and BSA-adjusted dose (82%, 73%-91%). PFS at 2 years for all studies was 77% (SD 68%-85%) and did not differ between fixed-dose (80%, SD 68%-93%) and BSA-adjusted dose (74%, SD 62%-86%). ORR for all studies was 86% (SD 79%-92%) and did not differ between fixed-dose (86%, SD 76%-96%) and BSA-adjusted dosage (84%, SD 80%-88%). CRR for all studies was 70% (SD 61%-80%) and did not differ between fixed-dose (67%, SD 54%-81%) and BSA-adjusted dose (77%, SD 64%-89%). Heterogeneity tests performed according to available clinical outcomes yielded results between 0% and 76%. Conclusion: The result of our systematic review and meta-analysis combining 30 prospective studies and a total of 3573 patients with newly diagnosed DLBCL treated with frontline R-CHOP found no difference in clinical outcomes between patients treated with fixed-dose and BSA-adjusted dose prednisone. Our findings provide scientific evidence for the widespread practice of capping prednisone at the maximum dose of 100 mg daily for 5 days, potentially avoiding unnecessary adverse effects from BSA-adjusted dosing.

Background/Case Studies: A 79-year-old male was admitted to our institution with anemia, with a hemoglobin nadir of 5.5g/dL, and no recent transfusion history. Given a remote history of occult colonic bleeding, the working diagnosis was GI bleeding. The referring blood bank had reported “possible antibody to high prevalence antigens of the Kell system, suspected McLeod.” The American Rare Donor Program had been contacted and confirmed no Ku or KX negative blood was available in the United States. Study Design/Methods: Initial testing by our immunohematology reference lab showed that the patient's plasma reacted with all cells tested, including the patient's own red blood cells (RBCs). The patient had a positive DAT (W+ poly, W+ IgG and negative C3d). Further testing showed the plasma and eluate prepared from the patient's RBCs did not react with cells treated with dithiothreitol (DTT) and did not react with an RBC designated as K0. Red cell morphology and creatinine kinase measurements were not consistent with the McLeod phenotype. The antibody was interpreted as having anti-Ku specificity. A serologic phenotype was performed on the patient's RBCs following treatment with chloroquine diphosphate and showed the following results: K-k-, Kp(b-), Js(b-) and Ku-. A molecular phenotype using Immucor Precise type gave the following results: K-k+, Kp(a-b+), Js(a-b+). Results/Findings: A sample was sent to the American Red Cross National Molecular Laboratory for KEL-cDNA analysis and genotype for KX blood group system. The probable genotype was KEL*02/KEL*02 with a predicted phenotype of K-k+, Kp(a-b+), Js(a-b+). The probable genotype was XK*01 (homozygous or hemizygous) with a predicted phenotype of Kx+. Given the positive DAT and the absence of an identifiable source of GI bleeding, a diagnosis of autoimmune hemolytic anemia with suppression of Kell system antigens was made. The patient was initially treated with 100mg oral prednisone daily for two weeks with subsequent weekly taper, four doses of 1g/kg IVIg daily, four doses of rituximab weekly, and three doses of daratumumab on weeks 1, 2 and 4. During the initial work-up and treatment, the patient did not receive a transfusion. Testing was repeated 3 months later: the DAT remained W+ and the antibody reactivity now demonstrated apparent anti-Jsb specificity. However, serologic antigen typing using chloroquine diphosphate now showed the following results: k+, Kp(b+), Js(b+) and Ku+. At this time, the patient's hemoglobin increased to a maximum of 11.6g/dL. Unfortunately, the patient relapsed about 4.5 months after his initial presentation. He was restarted on 100mg oral prednisone daily for two weeks followed by weekly taper. This led to only a modest improvement in his hemoglobin concentration. The DAT and phenotyping results remained unchanged but the antibody identification now demonstrated apparent anti-k (Cellano) specificity during this period. As the patient continued to have symptomatic anemia, in the setting of massive splenomegaly, the was decision made to proceed to splenectomy. During the operation, the patient received two K- units that were otherwise not typed for additional Kell system antigens. In the four weeks post-transfusion, there was no evidence of an acute worsening of his hemolytic anemia. Conclusions: This is a case of an autoantibody with apparent specificity to a high prevalence KEL antigen(s). The antibody was originally thought to be an alloantibody, requiring Ku- or Kx- RBCs. The KEL system antigens were depressed due to the patient's disease state and were re-expressed following treatment with multimodal immunomodulatory treatment. Specificity of the antibody appeared to change during therapy reacting more strongly with different high incidence Kell system antigens. When the patient was transfused with K- RBCs later in his disease course, there was no acute worsening of hemolysis. This finding is consistent with an autoantibody rather than an alloantibody to KEL antigen(s). This case shows the importance of incorporating molecular testing along with serology.

We report the second known case in the world of a rare beta chain variant hemoglobinopathy Hemoglobin Little Venice [β42 Phe→Cys, HBB:c.128T>G] originally found in 2009 in a 7 month-old Asian Indian female with severe chronic hemolytic anemia during infancy who is now 15 years of age. Her newborn hemoglobinopathy screen showed FA. She presented with jaundice at 1 month of age with a bilirubin of 15 mg/dL initially attributed to breast milk and was managed with supportive care. Hemoglobin electrophoresis with confirmatory DNA sequencing was performed by Mayo Clinic laboratories at 7 months of age to establish the diagnosis. At that time hemoglobin was 5.6 g/dL and bilirubin was 6.9 mg/dL. Hemoglobin electrophoresis showed Hb A 71.6%, Hb A2 2.5%, Hb F 24.5% and Hb variant 1.4%. Stability studies were abnormal. The testing revealed a previously undescribed beta 42 mutation of TTT>TGT (Phe>Cys). Our patient has been receiving blood transfusions every four weeks leading to iron overload at 5 years of age treated with an iron chelator. Her growth and development have been normal, similar to peers. At age 9, she had cholecystectomy for gallstones. At the age of 11, she had SARS COVID-19 infection that was treated with supportive care and she recovered well. She was noted to have mild thrombocytopenia ranging from 70-110's and had splenectomy at 13 due to increased frequency of blood transfusion and chronic splenomegaly. At 14, she was treated for asymptomatic babesiosis with atovaquone and azithromycin. At present, she continues to require regular transfusions every 4 weeks due to severe hemolytic anemia and has significant thrombocytosis along with leukocytosis and nucleated red blood cells. She has significant transfusion-associated hemosiderosis and receives double chelation with deferasirox and deferiprone with marked history of noncompliance. Last MRI of Liver T2* in 2023 showed an approximate hepatic iron concentration of greater than 20 mg/g that is significantly elevated and MRI of heart T2*decay time of greater than 20 ms, which indicates low risk of clinically significant myocardial iron deposition. Both parents and two sisters have no evidence of hemolytic anemia and there are no other family members with chronic anemia or history of splenectomies. The importance of phenylalanine in position 42 was described by Bartram et al in 2012 for the position's role in maintaining the solubility and stability of the β-hemoglobin chain. When replaced with cysteine, it disrupts oxygen delivery to the cells. This rare hemoglobinopathy requires multiple transfusions to treat vaso-occlusive episodes. At present, little is known regarding treatment choices for this rare hemoglobinopathy therefore, we will continue chronic blood transfusions and encourage compliance with iron chelation. A similar variant affecting the same codon, Hb Hammersmith [β42 Phe→Ser, HBB:c.128T>C] has comparatively more data in the literature which may offer some general guidance.

Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy, driven by IgG antibodies (Abs) that target platelet factor 4 (PF4) bound to heparin, resulting in platelet activation and a pro-thrombotic state. The PF4/Heparin (PF4/H) ELISA is the most commonly used screening assay for HIT due to its wide accessibility and high sensitivity. Despite its limited specificity, resulting in only a small fraction of positive cases progressing to actual HIT, PF4/H ELISA remains a critical tool in initial diagnostics. It is generally believed that HIT patients produce two types of Abs - those that bind to PF4/H and may or may not activate platelets. However, there are documented but rare HIT cases with an atypical profile: Abs testing negative in the PF4/H ELISA (ELISA-) but capable of platelet activation, suggesting the presence of a third type of Abs - those that activate platelets but can't recognize PF4/H complex. Since a PF4/H ELISA- result typically excludes an HIT diagnosis, overseeing these cases could lead to the resumption of heparin, potentially resulting in life-threatening thrombosis. Additionally, in HIT cases with a positive ELISA test profile, or classic HIT cases, levels of platelet-activating Abs and PF4/H-reactive Abs are not always correlated, suggesting the presence of ELISA- platelet-activating Abs. We thus investigated whether ELISA- platelet-activating Abs are present in classic HIT. To identify and characterize ELISA- Abs at the serological level, we firstly purified IgG Abs from the plasma of 5 healthy donors (HD) and 8 HIT patients using protein A beads, followed by the depletion of PF4/H-binding Abs using PF4/H-coated Sepharose beads. The efficiency of IgG purification and PF4/H-specific IgG depletion was confirmed by IgG and PF4/H ELISA. P-selectin expression assay (PEA) was conducted to evaluate the platelet activating ability of purified IgG pre and post depletion of PF4/H-specific Abs. We found that variable, but significant levels of platelet-activating Abs exist in the PF4/H non-reactive IgG portion in all 8 HIT samples, but none of the HD samples. Closely resembling those found in the PF4/H-reactive Abs in HIT patients' plasma, platelet activation induced by post-depletion Abs relied on exogenous PF4 and FcγRIIa and was inhibited by high-dose heparin. These data demonstrate that PF4/H non-reactive IgG Abs coexist with PF4/H-reactive Abs and may contribute to platelet activation in HIT patients. To verify these findings at the clonal level, we conducted single B-cell culture to induce antibody secretion by the cultured B cells from patients experiencing clinical manifestations of HIT. We screened clonal Abs made by 1506 single IgG1+ B cells isolated from peripheral blood mononuclear cells (PBMCs) of seven HIT patients and identified 18 clones capable of platelet activation. Of these, 13 were unable to bind to PF4/H. The functionality of these Abs was confirmed by recombinant Abs derived from single B-cell clones. This finding suggests that PF4/H non-reactive platelet-activating Abs exist at a higher frequency than those that bind to PF4/H. Interestingly, even though these Abs tested negative in the PF4/H ELISA, they were able to bind to the surface of PF4-treated platelets, and their platelet activation ability correlated with platelet binding affinity, suggesting a potential method for their detection. In summary, our study identified a novel group of potentially pathogenic Abs in HIT that, while unable to recognize the PF4/H complex, can bind to the PF4-coated platelet surface. These Abs frequently coexist with PF4/H-binding pathogenic Abs and may contribute to HIT pathogenesis. These insights will enrich our understanding of HIT pathogenesis and may pave the way for more advanced diagnostic and therapeutic strategies.

Introduction: Red blood cell (RBC) transfusion is a lifesaving intervention with a low but persistent risk of transfusion-transmitted infection. Amustaline/glutathione RBC pathogen-reduction (PR) technology is designed to proactively inactivate a broad spectrum of viruses, bacteria, protozoa and leukocytes by chemically crosslinking nucleic acids and preventing replication and transcription. The Red Cell Pathogen Inactivation (ReCePI) trial was a Phase III, double-blinded, randomized non-inferiority study comparing PR and conventional RBCs for the support of acute anemia. Methods/Study Design: Complex cardiac or thoracic-aorta surgery patients received conventional (Control) or PR RBCs (Test) during and for 7 days after surgery. The protocol was conducted with ethics committee approval at all participating centers and written informed consent from all participants. Hemoglobin levels, blood utilization and serum creatinine were assessed as indicators of efficacy and oxygenation of tissues (Karkouti et al. Br J Anaesth. 2012; 109 Suppl 1: i29-i38). The primary endpoint was the incidence of acute kidney injury (AKI) measured as change in serum creatinine from baseline within 48 hours of surgery, a predictor of adverse postoperative outcomes including mortality by Day 30 post-surgery (Lassnig et al. Am Soc Nephrol 2004; 1597-1605). Secondary endpoints included AKI occurring up to 7 days post-surgery (KDIGO Clinical Practice Guideline for AKI, Kidney Inter, Suppl. 2012;2:1-138); death or the need for renal replacement therapy by 30 days post-surgery; PR RBC-specific antibodies; and death by day 75 post-surgery. With >292 subjects enrolled, the study had 80% power to demonstrate non-inferiority, assuming an AKI incidence of 30% with conventional RBCs and a non-inferiority margin of half the conventional RBC rate. Under these circumstances, an absolute treatment increase of 5% in the AKI rate in the PR RBC arm would fail the non-inferiority test. This work was supported by a contract with the US Biomedical Advanced Research and Development Authority (HHS010020160009c) with Cerus Corporation. Results: Five-hundred and eighty-one subjects were randomized and 321 (55%) transfused in 18 US hospitals. In the modified intent-to-treat analysis subjects receiving Test and Control RBCs had similar median [IQR] total blood loss (1500 [940-2475] mL Test, 1733 [1060-2880] mL Control, p=0.310) and comparable median hemoglobin levels at baseline and immediately post-surgery (9.8 [8.9-10.9] g/dL Test, 9.6 [8.6-10.6] g/dL Control, p=0.157) and for 7 days after surgery, The PR RBC arm was transfused with fewer RBCs, measured as total RBC Hb transfused over 7-days (169.0 [102.0-240.0] g Hb PR arm, 188.0 [126.0-295.0] g Hb, conventional RBC arm, p=0.008). The incidence of AKI was 29.3% (46/157) for Test and 28.0% (45/161) for Control. The treatment difference was 0.74% (95% CI -8.9, 10.4%, non-inferiority margin 14.0%, p=0.001 for non-inferiority). Non-inferiority was also achieved by the per protocol analysis. Average mean change in serum creatinine within 48 hours of surgery was comparable (Test 0.020, Control 0.23 mg/dL, P=0.515). Adverse events, serious adverse events and deaths on study were not different. Five of 159 (3.1%) PR RBC recipients developed low titer PR RBC-specific antibodies without clinical signs of hemolysis. Flow cytometry analysis revealed persistent circulating PR RBCs with uniform antigen loss (modulation). Low level human IgG antibody binding was demonstrated in 3 of 5 subjects. Conclusions: PR RBCs showed equivalent hemoglobin support for acute bleeding patients undergoing cardiac or thoracic-aorta surgery while using less transfused total RBC Hb over 7 days. The incidence of AKI in patients transfused with PR RBCs was non-inferior to that observed with conventional RBCs, indicative of effective tissue oxygenation. Treatment-related antibodies to PR-RBC were observed only in Test subjects, the antibodies were low titer, transient, without clinical hemolysis, and persistent circulating PR RBCs were detected with modulated low level acridine antigen expression (www.clinicaltrials.gov #NCT03459287).

Introduction: Post-Cardiopulmonary Bypass (CPB) coagulopathy results in bleeding, transfusion and re-exploration, and increases morbidity, mortality and cost. Some studies have reported a relationship between individual factor levels and chest tube drainage as a marker of bleeding, but few have reported that relationship for multiple factors. Methods: With IRB approval and informed consent, 98 patients, ages 18 - 85, undergoing cardiac surgery with cardiopulmonary bypass (CPB) were studied. Factor levels measured five minutes post-protamine included fibrinogen (FIB), and factors II, V, VII, VIII, Von Willebrand Factor Antigen (VWF Ag), Ristocetin Cofactor (VWF Activity), IX, X, XI and XIII. Linear regression models examined the relationship between factor levels and post-op chest tube drainage over 24 hours as a surrogate marker for bleeding. An effect size (ES) was calculated so that each factor deficiency multiplied by the ES and the patient's weight in kg would estimate the contribution of that factor to bleeding. Factors were ranked from most to least impact on bleeding. Conversely, said ES would estimate the decrease in bleeding achieved by a percentage increase in a deficient factor level if such factor was known to be deficient. Results: F:II was 1st (most associated with bleeding), ES = -0.137, 95% CI -0.214 - -0.059, p < 0.001; F:X was 2nd, ES = -0.130, 95% CI -0.202 - -0.058, p < 0.001; F:VII ES = -0.121, 95% CI -0.198 - -0.045, p = 0.002; F:XI ES = -0.109, 95% CI -0.16 - -0.058, p < 0.001; F:IX ES = -0.100; 95% CI -0.135 - -0.065, p < 0.001; F:V ES = - 0.065; 95% CI -0.114 - -0.016, p = 0.011; F:XIII ES = - 0.055; 95% CI -0.099 - -0.011, p = 0.016; FIB ES = - 0.042; 95% CI -0.063 - -0.022, p < 0.001; F:VIII ES = - 0.007; 95% CI -0.020 - 0.006, p = 0.318; VWF Ag ES = 0.002; 95% CI -0.016 - 0.019, p = 0.855; VWF Activity ES = 0.004; 95% CI -0.015 - 0.023, p = 0.671. Conclusions: Factors VIII, VWF Ag and Ristocetin Cofactor demonstrated no relationship with bleeding, perhaps because they are elevated as acute-phase reactants. In theory, raising F:II level post-CPB by 30% in an 80 kg patient might decrease bleeding by 328 ml, and raising F:X level post-CPB by 30% in an 80 kg patient might decrease bleeding by 312 ml, etc. A weakness of this study is that the sample size was too small to perform a multi-variate analysis considering all factor levels. Still, the data suggest four-factor prothrombin complex concentrate (PCC) might be a more effective treatment for post-CPB coagulopathy than FFP. The data do not confirm cause and effect; that would require a large study with control and treatment arms. If multiple factor levels could be measured in a rapid and cost-effective manner it might aid in targeted treatment of post-CPB coagulopathy. The data suggest that work should be performed to better elucidate the contribution of coagulation factor deficiencies to post-CPB bleeding, as improved treatment of such factor deficiencies might decrease bleeding and transfusion requirements.

Introduction: The development of increasingly sensitive tests for the detection of measurable residual disease (MRD), such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) assays, has changed clinical practice in acute lymphoblastic leukemia (ALL). IGH V(D)J-based NGS MRD is the most sensitive assay to predict relapse in patients (pts) with B-ALL (Short, Blood Adv 2022). However, data regarding the use of T-cell receptor (TR) NGS MRD in T-ALL are limited and recent reports from pediatric cohorts suggest that persistent TR MRD may not predict relapse in T-ALL (Roy, ASH 2023, abstract 2976). With limited options for the treatment of relapsed/refractory T-ALL, accurate prediction of high relapse risk may provide an opportunity for early intervention. In this study, we evaluated the prognostic utility of TRB/TRG NGS MRD and its correlation with MFC MRD in adult patients with T-ALL. Methods: We retrospectively evaluated the MRD data and clinical outcomes of precursor T (pre-T) and early T precursor (ETP) ALL patients treated at four academic centers in the US. MRD was evaluated using MFC in CLIA-certified labs at individual sites with a sensitivity of 10-4, and the clonoSEQ (Adaptive Technologies, lnc) NGS assay, with a sensitivity of 10-6. Pts were included if they had a trackable TR clone and NGS MRD remission assessment in at least one time point. The correlation between the percentage of MRD by MFC vs NGS was calculated with the Pearson correlation coefficient, using every available MRD assessment for T-ALL pts in complete remission. Relapse-free survival was stratified based on NGS MRD level at the time of post-induction and post-consolidation assays, and comparisons were made with the log-rank test. The positive predictive value (PPV) for relapse of NGS MRD was calculated for pts with MRD > 10-6 at the post-induction and post-consolidation period. Results: A total of 19 pts who met our inclusion criteria, with a median age of 30 years (range, 18-65). 9 pts (47%) had ETP-ALL, 10 pts had pre-T ALL. Pts had a trackable TRB/TRG clone in 76% of cases, with 66% having a trackable TRG clone and 38% having a trackable TRB clone. 10 pts (53%) were treated with a modified AALL0434 regimen as first line therapy, 6 pts (32%) were treated with CALGB10403, 1 pt (5%) was treated with hyperCVAD, 1 pt (5%) was treated with a BFM regimen, and 1 pt (5%) was treated with CALGB9511. Out of 11 T-ALL pts with MRD data available post-induction, 6 pts (55%) had detectable MRD by NGS and no detectable MRD by MFC. Out of 13 pts with available post-consolidation MRD data, 2 pts (15%) had undetectable MRD by both NGS and MFC and 9 pts (69%) had detectable MRD by NGS only. There were no pts with detectable MRD by MFC and undetectable MRD by NGS at either timepoint. A total of 64 MRD data points from 19 pts were available to evaluate MRD correlation by MFC vs NGS, for which the Pearson correlation coefficient showed a statistically significant linear correlation (p < 0.01). At post-induction, 9 pts had NGS MRD > 10-4 and 2 pts had NGS MRD < 10-4. With a median follow-up time of 19.8 months, pts with NGS MRD > 10-4 had a median RFS of 19.8 months and pts with NGS MRD < 10-4 had a median RFS of 14.8 months. The log-rank test comparing RFS between these two groups was not statistically significant (p= 0.18). Persistent NGS MRD at post-induction had a PPV for relapse of only 18%. At post-consolidation, 7 pts had NGS MRD > 10-4, 4 pts had NGS MRD < 10-4, and 2 pts had undetectable MRD by NGS. With a median follow-up time of 17.3 months, pts with NGS MRD > 10-4 had a median RFS of 15.3 months and pts with NGS MRD < 10-4 or undetectable had a median RFS of 20.6 months. The log-rank test comparing RFS between these two groups was not statistically significant (p= 0.6). Persistent NGS MRD at post-consolidation had a PPV for relapse of only 27%. Conclusion: Despite statistically significant linear correlation between MFC and NGS MRD testing, there were no RFS differences between pts with NGS MRD > 10-4 vs NGS MRD < 10-4. All patients had persistent NGS MRD post-induction, which is markedly lower than the reported 20-25% NGS undetectable MRD rate in B-ALL post-induction. Persistent NGS MRD has low PPV for relapse in T-ALL, which limits its utility in clinical decision making for this population.

Background: Enterococci are the third most common cause of healthcare-associated infections in the United States, affecting 10-12% of all transplant recipients worldwide. Approximately 46% of patients with acute myeloid leukemia (AML) were found to be colonized with Enterococcus [1]. The risk of infection and its complications increases in patients treated with hematopoietic stem cell transplantation (HSCT). Given the high rates of Enterococcus colonization, we aimed to study the impact of Enterococcus infection in AML patients treated with HSCT. Methods: We conducted a retrospective analysis using the National Inpatient Sample Database (2018-2021). Adults over the age of 18 who were treated with HSCT for AML and had Enterococcus infections were identified using ICD-10 codes [2]. We performed the analysis using descriptive statistics and multivariate regression, with a p-value of less than 0.05 considered significant. Results: Of 40,462 HSCT patients, 1.3% (n=531) were admitted with Enterococcus infection. Among the HSCT recipients, Enterococcus infection was seen in 344 (1.4%) of 23,930 patients with all forms of Leukemia and in 134 (2.4%) of 5,693 patients with AML. There were no significant differences in sociodemographic factors such as age over 60 years, gender, or race between those with and without Enterococcus infection in the AML population (p>0.5). The AML-Enterococcus cohort had longer hospital stays (20.8 vs. 9.5 days, p<0.001) and higher total costs as compared to the AML-non-Enterococcus cohort ($373,619 vs. $147,075, p<0.001). Additionally, the AML-Enterococcus cohort had a higher prevalence of urinary tract infections (28.4% vs. 5.2%, p<0.001), fungal infections (13.4% vs. 8.6%, p<0.05), and acute respiratory failure (26.1% vs. 15.5%, p<0.001). Enterococcus infection was more common among patients with bone marrow dysfunction such as neutropenia (33.6% vs. 20.9%, p<0.001), anemia (79.9% vs. 57.6%, p<0.001), and pancytopenia (61.9% vs. 42.7%, p<0.001). Enterococcus infection also was associated with higher rates of severe sepsis (22.4% vs. 9.4%, p<0.001) and vasopressor usage (6.7% vs. 3%, p<0.05). Crude analysis indicated a higher mortality rate in the AML-Enterococcus cohort compared to the AML-non-Enterococcus cohort (16.1% vs. 8.8%, p<0.05). However, after adjusting for confounders, the mortality risk between the two cohorts was not significantly different (adjusted odds ratio 0.9, 95% CI 0.4-1.7, p>0.05). Similarly, the utilization of palliative care services did not differ between the two cohorts (12.7% vs. 9.8%, p>0.05). Conclusion: Enterococcus infection in the AML population who undergo HSCT poses a significant healthcare burden, resulting in longer hospital stays and higher healthcare costs. Patients with bone marrow dysfunction are at increased risk of Enterococcus infection and other opportunistic infections. For AML patients who have previously undergone transplantation and are hospitalized for sepsis, urinary tract infection, or respiratory failure, aggressive treatment with broad-spectrum antibiotics for Enterococcus is necessary. Due to the high crude mortality rate, it is essential to provide multidisciplinary care to reduce hemodynamic compromise and the potential need for vasopressor usage in these patients. It is important to consider Enterococcus as a differential diagnosis for any AML patient with HSCT presenting with a urinary tract infection or respiratory failure. Early recognition and treatment of Enterococcus infection could prevent lengthy hospital stays and reduce costs. References: Scheich S, Lindner S, Koenig R, et al.: Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia. Cancer. 2018, 124:286-96. 10.1002/cncr.31045 2021 ICD-10-CM. Accessed: July 14, 2024. https://www.cms.gov/medicare/coding-billing/icd-10-codes/2021-icd-10-cm.

Introduction: Tissue biopsies are needed to establish a diagnosis of systemic AL amyloidosis. Biopsy can be obtained from an involved organ with suspected amyloid deposition (target biopsy) or from sites in which amyloid commonly deposits (surrogate biopsy). The choice of biopsy site depends on institutional and physician preference. Two commonly used sites for surrogate biopsies are abdominal fat pad and bone marrow. The present systematic review and meta-analysis aims to evaluate the diagnostic test accuracy of fat pad and bone marrow biopsies as surrogate biopsy sites in the diagnosis of AL amyloidosis. Methods: As part of the ASH AL Amyloidosis Diagnostic Guideline, we performed systematic reviews for seven prioritized PICO questions related to the screening, diagnosis and organ involvement evaluation of AL amyloidosis. We conducted electronic searches on PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception until January 2024. Two reviewers independently and in duplicate performed title and abstract screening and full text article screening on LASER AI, with conflicts resolved by a third reviewer. Studies were eligible if they included patients that had a fat pad sample or bone marrow biopsy and a target organ biopsy for suspicion of AL amyloidosis allowing for the calculation of diagnostic test accuracy measures. Diagnostic test accuracy measures of interest were sensitivity, specificity, positive and negative predictive value. Statistical analysis was performed on OpenMeta[Analyst]. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Results: After deduplication, we retrieved 29,237 studies.. 20 studies with 2955 patients reporting on bone marrow biopsy, 25 with 4702 patients on fat pad sampling were included. The pooled sensitivity for bone marrow biopsy was 55.1% (95% CI 45.8-64.0, I2 = 94%) (Certainty of evidence: Low ⨁⨁◯◯), For fat pad sampling sensitivity was 76.6% (95% CI 72.1-80.8, I2 = 84.2%) (Certainty of evidence: Moderate ⨁⨁⨁◯). Among the included studies, 1 evaluated the sensitivity of fat pad sampling and bone marrow biopsy combined and found it to be 89%. No included studies evaluated specificity for bone marrow biopsy or fat pad sample. Conclusion: Combination of fat pad and bone marrow biopsy together significantly improve sensitivity for amyloid detection compared to either fat pad sampling or bone marrow biopsy alone.

Abstract Patient-reported outcomes (PROs) are associated with treatment outcomes in multiple myeloma (MM) in the clinical trial setting. However, most PRO tools are time consuming, which hinders use in routine practice. Our institution incorporated a “Hematology Patient-Reported Symptom Screen” (HPRSS), a 3-item questionnaire for fatigue, pain, and quality of life (QOL). The main objective of this study was to evaluate the impact of these symptoms on progression-free survival (PFS) and overall survival (OS) in a real-world cohort of patients with newly diagnosed MM. This retrospective study included patients with MM diagnosed between April 2011 and December 2017, seen at Mayo Clinic (Rochester, MN), who completed the HPRSS. Patients rated their symptoms on a scale from 0 to 10. Clinically relevant symptoms were defined as scores ≥5 for pain and fatigue, and ≤5 for QOL. At diagnosis, 735 patients had scores for all domains. The median follow-up was 8.1 years. Age was associated with increased odds of fatigue and decreased QOL. Female sex and comorbidities were associated with fatigue and pain. Higher disease stage, anemia, lytic lesions, and increased plasma cell burden were associated with fatigue, pain, and decreased QOL. Clinically relevant fatigue, pain, and decreased QOL were associated with decreased PFS and OS. On multivariate analysis including age, International Staging System III, high-risk cytogenetics, and postinduction transplantation, fatigue and decreased QOL were independently associated with decreased OS. A composite HPRSS score stratified patients into 3 groups with distinct OS. Patient-reported symptoms are prognostic in patients with newly diagnosed MM. The prognostic values of fatigue and decreased QOL are independent of age, disease stage, and transplant status.