BACKGROUND:Cancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC. METHODS:In vitro T cell stimulation was performed in the presence of sPD-L1 to evaluate its immunomodulatory activity. Data from The Cancer Genome Atlas (TCGA) were investigated for PD-L1 splice variants and enzymes involved in proteolytic cleavage (i.e. ADAM10). Plasma from 74 NSCLC (stage IA-IIIB), as well as an additional 73 (control cohort) patients was collected prior to curative surgery. Thereafter sPD-L1 levels from an immunosorbent assay were correlated with patient outcome. RESULTS:In vitro sPD-L1 inhibited IFN-γ production and proliferation of T cells and induced a terminal effector CD4 T cell subtype expressing CD27. Data from the TCGA demonstrated that elevated mRNA levels of ADAM10 is a negative predictor of outcome in NSCLC patients. To investigate the clinical relevance of these in vitro and TCGA findings, we quantified sPD-L1 in the plasma of early-stage NSCLC patients. In the first cohort we found significantly higher sPD-L1 levels in relapsing NSCLC patients, with a multivariate analysis revealing high sPD-L1 (>1000 pg/mL) as an independent predictor of survival. However, these findings could not be validated in two independent control cohorts. DISCUSSION:Although in vitro and TCGA data support the suppressive effect of sPD-L1 we were unable to translate this in our clinical setting. These results may be due to the small patient number and their heterogeneity as well as the lack of a standardized sPD-L1 ELISA. Our inconclusive results regarding the value of sPD-L1 in early stage NSCLC warrant assay validation and further investigation in larger (neo-)adjuvant trials.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) and Burkitt lymphoma (BL) are uncommon, highly aggressive diseases originating either from immature precursor T cells or from mature B cells in BL. We retrospectively analyzed the outcome of an early autologous and/or allogeneic stem cell transplantation (SCT) concept in 28 patients with advanced stage T-ALL/LBL and BL after three to four remission induction/consolidation chemotherapy cycles. Considering only patients in first complete remission (CR), the 5-year overall survival (OS) and event-free survival (EFS) was 91% in patients with BL and 73% in patients with T-ALL/LBL with a 5-year relapse incidence (RI) of 9% in patients with BL and 27% in patients with T-ALL/LBL. All relapsing patients finally succumbed to the disease (n = 10) or complications/toxicity after having received a salvage allogeneic transplant (n = 5). Despite the low patient number our retrospective single-centre analysis by incorporating an early intensive high-dose chemo-/radiotherapy strategy with either autologous or allogeneic stem cell transplantation, although preliminary, show promising long-term outcome. Further studies are highly warranted to better define those patients who might benefit most from such a treatment approach.

Book Citations: Authors, Title, HemaSphere, 2023;7(S3):pages. The individual abstract DOIs can be found at https://journals.lww.com/hemasphere/pages/default.aspx. Disclaimer: Articles published in the journal HemaSphere exclusively reflect the opinions of the authors. The authors are responsible for all content in their abstracts including accuracy of the facts, statements, citing resources, etc. 1128 19 patients (63%) were treatment naïve. In the previously treated cohort, prior lines of treatment included chemoimmunotherapy in 73% and ibrutinib + obinutuzumab + venetoclax, bendamustine + ibrutinib + ofatumumab and obinutuzumab + venetoclax in 9% of patients each. At the data cut on the 24th of November 2022 the median observation time was eight months, 21 patients remained on therapy. Reasons for discontinuation were adverse events in five (56%) and death and withdrawn consent in two (22%) patients each, respectively. All patients experienced at least one AE, totaling in 200 AEs of which 35 (18%) were CTC grade >3 (patient level analysis is shown in Table 1). 15 severe adverse events were reported, of which eight (53%) were assessed as treatment-related by the investigator. There were no cases of severe (Grade ≥3) bleeding, two patients (6%) experienced atrial fibrillation with CTC grade two and three, respectively. Two cardiac SAEs termed cardiac failure were reported in patients who both had prior existing hypertension and atrial fibrillation. Four patients (13%) died, of which one death was deemed treatment related. Causes of death were infection in three cases (one bacterial and two COVID-19 pneumonia) and concomitant disease in one case. Summary/Conclusion: The first interim analysis of this international phase II study evaluating treatment with acalabrutinib in very old and/or frail patients with CLL did not show unexpected safety signals in comparison to prior published data. HemaSphere | 2023;7(S3) EHA2023 Hybrid Congress Copyright Information: (Online) ISSN: 2572-9241 © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. This is an open access Abstract Book distributed under the Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) which allows third parties to download the articles and share them with others as long as they credit the author and the Abstract Book, but they cannot change the content in any way or use them commercially. Abstract Book Citations: Authors, Title, HemaSphere, 2023;7(S3):pages. The individual abstract DOIs can be found at https://journals.lww.com/hemasphere/pages/default.aspx.Book Citations: Authors, Title, HemaSphere, 2023;7(S3):pages. The individual abstract DOIs can be found at https://journals.lww.com/hemasphere/pages/default.aspx. Disclaimer: Articles published in the journal HemaSphere exclusively reflect the opinions of the authors. The authors are responsible for all content in their abstracts including accuracy of the facts, statements, citing resources, etc. 1129 HemaSphere | 2023;7(S3) EHA2023 Hybrid Congress Copyright Information: (Online) ISSN: 2572-9241 © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. This is an open access Abstract Book distributed under the Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) which allows third parties to download the articles and share them with others as long as they credit the author and the Abstract Book, but they cannot change the content in any way or use them commercially. Abstract Book Citations: Authors, Title, HemaSphere, 2023;7(S3):pages. The individual abstract DOIs can be found at https://journals.lww.com/hemasphere/pages/default.aspx.Book Citations: Authors, Title, HemaSphere, 2023;7(S3):pages. The individual abstract DOIs can be found at https://journals.lww.com/hemasphere/pages/default.aspx. Disclaimer: Articles published in the journal HemaSphere exclusively reflect the opinions of the authors. The authors are responsible for all content in their abstracts including accuracy of the facts, statements, citing resources, etc. 1130

Downregulated C-type lectin domain family 3 member B (CLEC3B) is observed in NSCLC and is linked with immune cell infiltration. We aimed to analyse the impact of CLEC3B mRNA expression on survival and its molecular link to NSCLC subtypes and to immune cell infiltration. 19,892 samples were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (592 genes/WES), RNA (WTS) and IHC. Top quartile transcripts per million (TPM) were defined as high (Q4, ≥4.03 TPM) and bottom quartile as low (Q1, ≤0.89 TPM). Cell infiltration was estimated by QuantiSEQ. X2/Fisher-Exact were used and significance was determined as p-value adjusted for multiple comparison (q<0.05). Real-world overall survival (OS) information was obtained from insurance claims data. Median age was 69 years. High CLEC3B mRNA expression was associated with female sex (55.2% women vs 44.8% men, p<0.001). Adenocarcinomas vs squamous-cell carcinomas had higher CLEC3B expression (2.28 vs 1.51, q<0.001). CLEC3B correlated negatively with mutations in TP53 (74.7% in Q1 vs 52.4% in Q4), KEAP1 (15.9% vs 11.2%), RB1 (13.5 vs 9.2%), CDKN2A (13.0% vs 8.3%), NF1 (10.3% vs 6.9%) (all q<0.001). KRAS (31.8% in Q4 vs 25.6% in Q1), EGFR (17.2% vs 8.1%), STK11 (15.9% vs 11.3%) mutations were more frequently observed in CLEC3B high expressors (all q<0.001). High CLEC3B mRNA expression was negatively associated with high TMB (43.0% vs 29.0%) and high PD-L1 expression (62.5% vs 47.7%) (all q<0.05). Transcriptomics revealed an upregulation of various immunological markers (i.e. LAG3, INF-G, PDCD1) and a higher abundance of several immune cells (i.e. B cells, macrophages, T cells) in the CLEC3B high subgroup (all q<0.001). Patients with high CLEC3B mRNA expression showed an improved OS when compared to CLEC3B low expression (p<0.001, HR: 1.35); a similar observation was made in patients treated with checkpoint inhibitors (p<0.001, HR: 1.29). Our study represents the largest analysis of CLEC3B mRNA expression in NSCLC. High CLEC3B expression levels are linked to a distinct molecular/immunological profile and to improved survival. Further experiments are now ongoing to unravel functional aspects of CLEC3B biology in NSCLC.

Adult acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a rare and heterogeneous malignancy characterized by uncontrolled proliferation of B or T cell precursor cells. Here, we retrospectively analyzed the outcome of early autologous stem cell transplantation in standard-risk patients in first complete remission (n=24) and of allogeneic transplantation in high and highest risk, and relapsed/refractory patients (n=35). The 10-year overall survival after autologous transplantation was 45%. The 10-year overall survival after allogeneic transplantation was 58%. The cumulative incidence of relapse was 29% after allogeneic and 67% after autologous transplantation. The cumulative incidence of non-relapse mortality was 0% after autologous and 12% after allogeneic transplantation. This retrospective single center analysis in a limited number of standard-risk patients clearly demonstrates that early autologous transplantation in first complete remission leads to an acceptable long-term outcome with a short overall treatment duration of less than 6 months compared with more than 2 years with conventional chemotherapy. More sensitive and standardized methods to detect minimal residual disease (MRD) will further help to identify those patients more accurately who are most likely to benefit from such a short and intensive treatment strategy (i.e., MRD negative standard-risk patients) or those who require early targeted therapy (e.g., blinatumomab) in case of MRD positivity. Early allogeneic transplantation results in long-term survival/cure in nearly two-thirds of all high and highest risk, and relapsed/refractory patients.

Background and importance We present the case of a young patient with T lymphoblastic lymphoma (T-LBL) who developed severe toxicity after receiving an anthracycline based protocol that is generally well tolerated by healthy patients. We assume that the substitution of daunorubicin by doxorubicin due to a nationwide shortage of daunorubicin played a crucial role in developing severe toxicity. Aim and objectives The 19-year-old man with no previous illnesses was diagnosed in December 2019 with T-LBL, a rare, aggressive neoplasm of precursor T cells that progresses rapidly and requires prompt diagnosis and medical intervention. T-LBL shows morphological and immunophenotypical similarities to acute lymphoblastic leukaemia (ALL). T-LBL treatment is the same as for ALL. Material and methods The induction protocol consisted of dexamethasone, vincristine, daunorubicin and pegasparaginase. Due to a nationwide shortage, daunorubicin (30 mg/m²) was substituted by doxorubicin (25 mg/m²). Results Chemotherapy was initially well tolerated, but beginning on day 15, the patient developed pronounced mucositis and increased skin toxicity (hand–foot syndrome, grade IV). Moreover, coagulation parameters deteriorated, and repeated transfusions with erythrocytes and platelet concentrates were needed. After administration of pegasparaginase on day 31, liver values increased, and finally, the patient had to be transferred to the intensive care unit due to fulminant pancreatitis. After 3 days, the patient could be transferred back to our ward. However, within 2 weeks, the patient developed sensory disturbances in all extremities, which was classified as chemotherapy associated polyneuropathy. In the further clinical course, the patient‘s general condition improved, and PET-CT showed complete metabolic remission. Due to the severe chemotherapy associated side effects, intensive consolidation treatment, according to the protocol, was cancelled. Instead, a consolidating therapy with nelarabine was carried out without complications. To date (October 2020), the patient is in a good clinical condition and has not developed disease recurrence. Probability assessment using the Naranjo algorithm resulted in ‘probable adverse drug reaction’ (score=6). Conclusion and relevance Our case report underlines the fact that shortages of essential anticancer drugs can have a particular impact on the efficacy and safety of established chemotherapy regimens, as these medicines often have few or no proven effective alternatives. References and/or acknowledgements Patel S, et al. A single-centre experience of the nationwide daunorubicin shortage: substitution with doxorubicin in adult acute lymphoblastic leukaemia. Leuk Lymphoma 2013;54:2231–5. Conflict of interest No conflict of interest

In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. The median number of HCO hemodialysis sessions was 11 (range 1–42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.

We investigate the energy conversion process and subsequent thermal and bit-writing performance of a plasmonic near-field transducer (NFT) under steady-state operation within heat-assisted magnetic recording (HAMR) devices. The NFT is composed of metal-insulator-metal (MIM) layers that are designed to localize heating and produce optimal thermal gradients in order to relieve parasitic heating effects in the NFT. The thin-film MIM structure confines the electromagnetic energy in the down-track direction while cross-track confinement is achieved by tapering the insulator feature of the MIM. A comparative analysis using Gold and a number of novel Au alloys is undertaken. Modeled performance shows excellent thermal spot confinement (50 × 50 nm2) of temperatures above 650 K at an input laser power of 830 nm of less than 5 milliwatts. In addition, micromagnetic simulations using a stochastic Landau-Lifshitz-Bloch equation yield excellent signal to noise ratio with minimum jitter of under 2 nm when recording.

INTRODUCTION:The involvement of vital organs in multiple myeloma (MM) with systemic amyloid light-chain (AL) amyloidosis can lead to acute organ failure. In this case, the fear of recurrence or progression of multiple myeloma often excludes those patients from undergoing organ transplantation. Nevertheless, clinically fit patients might benefit from a different therapeutic approach. This case presentation might highlight this particular unmet need and strengthen a different treatment approach.CASE PRESENTATION:To our knowledge, we present the first case of successful simultaneous liver and kidney transplantation, followed by autologous stem cell transplantation in a 60-year-old Caucasian male patient suffering from MM (Durie-Salmon stage IIB; ISS-stage: III, RISS stage: III) with primary AL amyloidosis. Chemotherapy treatment led to end-stage kidney disease requiring dialysis. Liver failure also occurred after at least three cycles of CyBorD (bortezomib, cyclophosphamide, and dexamethasone) of induction therapy with a good hematologic response. Over three years after the initial diagnosis, the patient is reportedly showing an excellent quality of life and a complete remission.DISCUSSION AND CONCLUSION:We conclude that kidney and liver transplantation followed by autologous stem cell transplantation can be a treatment option for a selected group of patients with MM if AL amyloidosis is leading. In the end, the remission assessment by IMWG response criteria displayed a complete remission of MM together with complete reconstitution of organ functions (liver & renal function) as long as upfront clinical evaluation excludes significant cardiac involvement and other severe co-morbidities.

Increasing isolation rates of resistant bacteria in the last years require identification of potential infection reservoirs in healthcare facilities. Especially the clinical wastewater network represents a potential source of antibiotic resistant bacteria. In this work, the siphons of the sanitary installations from 18 hospital rooms of two German hospitals were examined for antibiotic resistant bacteria and antibiotic residues including siphons of showers and washbasins and toilets in sanitary units of psychosomatic, haemato-oncological, and rehabilitation wards. In addition, in seven rooms of the haemato-oncological ward, the effect of 24 h of stagnation on the antibiotic concentrations and MDR (multi-drug-resistant) bacteria in biofilms was evaluated. Whereas no antibiotic residues were found in the psychosomatic ward, potential selective concentrations of piperacillin, meropenem and ciprofloxacin were detected at a rehabilitation ward and ciprofloxacin and trimethoprim were present at a haemato-oncology ward. Antibiotic resistant bacteria were isolated from the siphons of all wards, however in the psychosomatic ward, only one MDR strain with resistance to piperacillin, third generation cephalosporins and quinolones (3MRGN) was detected. In contrast, the other two wards yielded 11 carbapenemase producing MDR isolates and 15 3MRGN strains. The isolates from the haemato-oncological ward belonged mostly to two specific rare sequence types (ST) (P. aeruginosa ST823 and Enterobacter cloacae complex ST167). In conclusion, clinical wastewater systems represent a reservoir for multi-drug-resistant bacteria. Consequently, preventive and intervention measures should not start at the wastewater treatment in the treatment plant, but already in the immediate surroundings of the patient, in order to minimize the infection potential.

Abstract This abstract was withdrawn by the authors. Citation Format: Schwab R, Clark A, Yau C, Wolf D, Chien AJ, Majure M, Ewing C, Wallace A, Roesch E, Helsten T, Forero A, Stringer-Reasor E, Vaklavas C, Nanda R, Jaskowiak N, Boughey J, Haddad T, Han H, Lee C, Albain K, Isaacs C, Elias A, Ellis E, Shah P, Lang J, Lu J, Tripathy D, Kemmer K, Yee D, Haley B, Korde L, Edmiston K, Northfelt D, Viscusi R, Khan Q, I-SPY 2 Consortium, Symmans WF, Perlmutter J, Hylton N, Rugo H, Melisko M, Wilson A, Singhrao R, Asare S, van't Veer L, DeMichele A, Berry D, Esserman L. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-02.