Abstracts of the Cell Therapy Transplant Canada 2023 Annual Conference

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2023 Annual Conference. The conference was held in-person, 31 May–2 June 2023, in Halifax, Nova Scotia at the Westin Nova Scotian hotel. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 1 June, and oral abstract authors were featured during the oral abstract session in the afternoon of Friday, 2 June 2023. Twenty-three (23) abstracts were selected for presentation as posters and four (4) as oral presentations. Abstracts were submitted within four categories: (1) Basic/Translational Sciences, (2) Clinical Trials/Observations, (3) Laboratory/Quality, and (4) Pharmacy/Nursing/Other Transplant Support. The top four (4) oral abstracts and top four (4) poster abstracts were selected to receive an award. All of these were marked as “Award Recipient” within the relevant category. We congratulate all the presenters on their research and contributions to the field.

CD56 dim NK cells to be associated with cGvHD development.We hypothesize that unique subpopulations of NK reg cells may be important in the induction of immune tolerance.
Purpose: To transcriptionally characterize the unique NK reg cell subpopulations among HSCT patients that associate with cGvHD development or suppression.
Methodology: Day 100 pediatric peripheral blood mononuclear cell samples were utilized from the ABLE (PBMTC 1202) trial, including samples from patients that developed cGvHD (n = 3) or no cGvHD (n = 4).Single-cell RNA sequencing (scRNAseq) was performed on isolated NK cells using the 10× Chromium machine (8000 cells/sample).Single-cell cDNA libraries were sequenced via Illumina Novaseq 6000 to a depth of ~30,000 reads/cell.Raw data from each sample were demultiplexed, aligned to a custom reference genome, and the unique molecular identifier (UMI) counts were quantified using 10× Genomics Cell Ranger software v3.0.0 (default parameters).Single-cell clustering was performed using the Seurat package (v3.0).Statistical analysis was performed using a Wilcoxon Rank-Sum or t-test.
Results: We investigated for unique NK cell subsets in patients with and without cGvHD.Single-cell transcriptome analysis revealed seven unique NK cell subsets, three of which strongly associate with cGvHD development or suppression.As previously described, we identified a significant cell increase in Cluster 0 (cytotoxic CD56 dim NK cells) in patients with cGvHD.Interestingly, we observed two distinct NK reg cell subpopulations associated with cGvHD suppression.We identified an increase in the cell proportions of Cluster 1 (classic CD56 bright NK reg cells) and Cluster 2 (Type I interferon-responsive NK reg cells) among immune tolerant patients (Figure 1).Clusters 1 and 2 are characterized by high expressions of the genes GZMK and XCL1 and IFIT2 and PMAIP1, respectively.In both NK reg cell subpopulations, the development of cGvHD was associated with the upregulation of AREG and GZMB (Table 1).SOC.Although the TB per SPD did not seem to impact axi-cel outcomes in ZUMA-7 (Locke, FL et al., ASCO 2022, abstract 7565), high MTV was associated with poorer outcomes with axi-cel vs. low MTV, and rates of grades ≥3 NEs and CRS were associated with higher MTV.This suggests that MTV is a more accurate and sensitive measure of TB vs. SPD.Nevertheless, axi-cel was superior to SOC irrespective of the MTV subgroup, including among pts in the high-MTV subgroup.

Conclusion:
This study was able to validate the primary metabolome changes seen previously in a large pediatric cohort, including increases in α-ketoglutarate, glutamic acid, and kynurenine.The significant decrease in glutamine found in this study is consistent with the observed elevation in glutamic acid found in ABLE1.0 and ASCT0031, as these metabolites are usually inversely related.However, secondary metabolome changes, such as an elevation in 18:0SM and decreases in p-hydroxyhippuric acid and acetyl-ornithine, were not found in these data.Contact: tashi.rastogi@bcchr.ca;kschultz@mail.ubc.ca.Gaganvir Parmar 1,2 , David S. Allan 1,2 , Gail Morris 1 , Nicholas Dibdin 1 , Kathy Ganz 1 , Karen Mostert 1 , Kristjan Paulson 3,4 , Tanya Petraszko 1,5 , Nora Stevens 1 , and Matthew D. Seftel 1,5  tics and outcomes were obtained by retrospective medical chart review.This analysis is primarily descriptive.
Results: As of January 2023, 11 pts with r/r LBCL have received axicabtagene ciloleucel CAR T-cell therapy.All the pts had successful manufacturing, with turnaround times of 20-22 days, and the manufactured T-cells were infused following lymphodepleting conditioning with standard doses of fludarabine and cyclophosphamide.The clinical course and outcomes for nine patients were evaluable at the time of the abstract submission.Baseline pt characteristics are described in Table 1.The median age was 60 years (range: from 23 to 75 years) and 66% (n = 6) of the patients were female.Diffuse large B-cell lymphoma was the most common diagnosis (44%, n = 4), and pts had received a median of two prior lines of systemic therapy prior to receiving CAR T-cell therapy.The median hematopoietic cell transplant comorbidity index score at the time of the lymphodepletion was 1 (range: 0-3).The most common comorbidity was pulmonarycomplications.The median cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS) grades were 2 (range: 1-3) and 3 (range: 0-4), respectively.All the pts experienced CRS (11% > grade 3), and 88% experienced ICANS (55% > grade 3).There was no treatmentrelated mortality.At 30 days post CAR T-cell infusion, the overall response rate was 100%, with 55% (n = 5) achieving a complete metabolic response, and 44% (n = 4) achieving a partial response (Figure 1).

Conclusion:
In this cohort of real-world pts with r/r LBCL treated with CAR Tcell therapy, we observed high rates of overall responses.It is important to continue to collect and analyze these data for future pts to better understand our centre's patient population and areas where outcomes can be improved as our local program expands.Further multivariable analysis of the determinants of responses and toxicities are underway as more pts are treated.Methodology: This study included all the patients ≥18 years old referred for commercial CAR T-cell therapy before November 2022.Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method.

Conclusion:
Standard-of-care CAR T-cell therapy in Alberta has a manageable safety profile and favourable efficacy, which mirrors the results of clinical trials and other realworld studies.Further work is needed to optimize the geographic distance to treatment centres and to reduce the risk of drop-out prior to infusion, which represent significant barriers to the successful delivery of CAR T-cell therapy.Methodology: This is a retrospective single-centre study, where we have described the demographic and clinical characteristics of MM patients with high-risk cytogenetics at our centre who underwent a tandem autologous transplant (Auto-Auto) from 1 January 2017 to 1 January 2021.Secondary objectives looked at progression-free survival (PFS) and the overall survival (OS) using the Kaplan-Meier method.
Results: From 1 January 2017 to 31 December 2020, there were 25 high-risk patients who underwent tandem ASCT.Key patient characteristics are shown in Table 1.Translocation (4:14) was seen in 8/25 (32%) patients, t (14:16) in 5/25 (20%) patients, del17p in 7/25 (28%) patients, +1qamp in 8/25 (32%) patients, del1p + 1qamp in 5/25 (20%) patients, and more than one abnormality in 12/25 (48%) patients.In this high-risk group, the most common induction regimen consisted of cyclophosphamide, bortezomib, and steroids (CyBorD) in all the patients, with two patients transitioned to daratumumab, lenalidomide, and dexamethasone and PAD/CVD because of poor responses.Maintenance therapy was given to 19/25 (76%) post-tandem ASCT patients.In terms of responses, we recorded CR (complete response) vs. VGPR (very good partial response) vs. PR (partial response) after induction, 2-3 months after tandem #1, 2-3 months after tandem #2, 12 months after tandem #2, and 12 months after maintenance.Following induction, 16 patients had achieved VGPR, and nine patients had achieved PR.After the first tandem ASCT, five of the previous PR patients had achieved VGPR.In addition, 1-3 months post tandem #2 ASCT, three of the previous PR patients achieved VGPR, and two of the VGPR patients achieved CR.In addition, 12 months after tandem #2, two of the previous VGPR patients achieved CR, and one PR patient achieved VGPR.At the time of the median follow-up, 44% of the patients had relapsed, with a median of 60 months.One patient relapsed within 1-3 months post tandem #1 ASCT.Nine other patients relapsed post tandem #2 ASCT and during maintenance, except for one patient, who relapsed at the time of the tandem #2 ASCT.The 3-year PFS for patients who received tandem ASCT followed by maintenance was not reached (p = 0.0001).and double/triple-hit status, predicted failure to proceed to infusion.Lower absolute lymphocyte counts and elevated inflammatory markers at apheresis were increased in cancelled patients.1 summarizes the demographics and disease characteristics for pts who did or did not receive ASCT for 2L therapy.The median ages at the beginning of 2L were 55.5 y and 67.0 y for those who did and did not receive ASCT, respectively; the majority of pts were male in both groups (33 (75.0%) and 35 (66.0%)).Overall, 48 pts (44.0%) received ASCT (2L, 91.7%; 3L, 6.3%; 4L, 2.1%) and 15 pts (13.8%) received CAR T-cell therapy (2L, 0%; 3L, 66.7%; 4L, 33.3%).Of the 72 pts eligible for ASCT, 29 (~40%) did not proceed to transplantation.Chemorefractoriness (9 (37.5%)) and advanced age (10 (41.7%)) were the main reasons for ASCT ineligibility (Table 2).The most common prescribed 2L therapy for pts not receiving a transplant was gemcitabine, dexamethasone, and cisplatin ± rituximab (32%), followed by gemcitabine/oxaliplatin ± rituximab (5.2%) or bendamustine (5.2%).Pts who received conventional salvage chemotherapy in 3L and 4L had short median times to the next treatment (3.8 and 3.4 months, respectively).Background: Inadequate oral intake and treatment-induced malnutrition often result from side effects, like mucositis and GI disturbances, associated with autologous hematopoietic stem cell transplants (AHSCTs).The American Society of Enteral and Parenteral Nutrition (ASPEN) recommends nutritional support via enteral (EN) or parenteral (PN) nutrition in this patient population.PN is commonly used to address these side effects as the standard of care at our centre, secondary to central line catheter accessibility.
Purpose: To examine differences in transplant-related, biochemical, and nutritionrelated outcomes in AHSCT patients randomized to enteral vs. parenteral nutritional support groups.
Methodology: This (pilot) prospective randomized study was conducted at London Health Sciences Centre in London, ON, Canada.AHSCT patients (n = 37, 54% female) were recruited between 2019 and 2022 and randomized to receive either EN (46%) or PN (54%) support.Nutritional supports were initiated when oral intake fell below 80% of the estimated needs for energy and protein.Patients were assessed at three time points: baseline (at admission), day 15, and day 30 post transplant.Assessments included anthropometric (BMI), biochemical (albumin, pre-albumin, CRP, and blood glucose), nutritional (standardized phase angle (SPhA), bioelectrical impedance analysis (BIA), quadricep muscle layer thickness (QMLT), and handgrip strength (HGS)), and dietary measures (3-day food record).
Results: No significant differences were found between EN and PN groups for the length of the hospital stay or biochemical measures.The mean length of the nutritional support was 6.60 ± 3.40 and 10.63 ± 6.02 days for EN vs. PN, respectively.Over the study period, there were fewer incidences of gastrointestinal mucositis of any grade and fewer incidences of grade 3 in the EN group compared to the PN group, 35.5% vs. 55%, respectively.There were no significant differences between the groups at the baseline, day 15, or day 30 for SPhA.
Conclusion: Fewer cases overall and less-severe cases of GI mucositis were found in the enteral nutritional support group.Patients randomized to enteral vs. parenteral nutritional support did not have a longer length of stay in the hospital, nor were there any significant differences in laboratory measures and SPhA between the two groups.Our results support the use of enteral nutrition vs. parenteral to mitigate treatment-induced malnutrition in AHSCT patients.A multicentre study is needed to support these findings further.More data will be available and presented at the CTTC conference in June 2023.
Abstract 18 (Poster): The abstract was withdrawn.Purpose: We evaluated the outcomes of all the patients referred for CART and explored risk factors for early failure, as defined by the failure to receive cells, death within 100 days of infusion, or progressive disease (PD) by the first-response assessment.
Methodology: This is a single-centre retrospective review of all the patients with RR-DLBCL referred for CART at PM from June 2020 to August 2022.Eligible patients had RR-DLBCL after 2+ prior systemic therapies and had eGFR > 45 mL/min/1.73m 2 , LVEF > 40%, pulse oxygenation > 91% in room air, a performance status (KPS) of > 70%, and no active CNS disease.Tisa-cel was approved before axi-cel in Canada.
Results: A total of 148 patients (pts) were referred for CART during the study period.Of these, 107 (72%) received CART (tisa-cel 41 and axi-cel 66) (Table 1).The median time from acceptance for CART to infusion was 46 (19,100) days, 50 days (19,100), and 44 days (28-89) for all the pts, tisa-cel, and axi-cel, respectively.The median time from apheresis to infusion was 37 days (27,107), 43 days (35,107), and 34 days (27,69) for all the pts, tisa-cel, and axi-cel, respectively.The CRS of any grade occurred in 93/107 pts, with one grade 3+.Twenty-seven of the 107 pts developed ICANS, three (3%) developed grade 3+ ICANS.Eight required ICU support (8%) (2 ICANS, 2 CRS, and 4 Other) The response at 100 days was assessed in 107 pts: 34 achieved CR/CMR (32%), 12 achieved PR (11%), 34 (32%) experienced progression, and two (2%) died before 100 days; the 100-day status was unknown/pending in 25 (23%) patients.The median OS from consultation was 12.91 months for the cohort and 25.79 months among patients receiving CART.The median survival for patients not infused with CART was 2.46 months (Figure 1).The median follow-up times from infusion were 6.93 months, 20.76 months, and 5.75 months for all infused pts, tisa-cel, and axi-cel, respectively.The median PFS was 8.26 months, 1.91 months, and not-yet reached (NYR) for all the infused pts, tisa-cel, and axi-cel (p = 0.02).The median OS was 24.21 months, 12.32 months, and NYR for all the infused pts, tisa-cel, and axi-cel (p = 0.20), respectively.A univariate analysis of the predictors for early failure was conducted.Those with an unknown status at day 100 were excluded.A total of 123 pts were included, and 75 (61%) pts met the definition of early failure.The examined variables included the stage, ECOG score, presence of bulky disease (>7 cm), relapsed/refractory disease, lymphoma subtype, cell of origin, presence of double-hit or triple-hit lymphoma, and failure to undergo ASCT.Only the failure to undergo ASCT was significant (p = 0.002).
Curr.Oncol. 2024, 31, FOR PEER REVIEW 24 Conclusion: We present the early experience with SOC CART for RR-DLBCL from a large tertiary Canadian centre.Our results are similar to other RWEs.Limited RW cohorts have provided ITT results.A large proportion of referred patients experienced early failure, with 27.7% not receiving CART.Improved pt selection criteria are worthy of further investigation.59.9 (12.4) 59.1 (12.8) 62.1 (12.2) 57.2 (12.9)Sex Escarpment Cancer Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada Background: Allogeneic stem cell transplant (SCT) is one of the few currently available therapies to cure acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Positive outcomes are dependent on the engraftment of donor cells to provide hematopoiesis as well as a graft-versus-tumor effect.The measurement of the whole-blood (WB) and T-cell (TC) chimerism at routine intervals post SCT allows for the monitoring of the engraftment, particularly in settings where more sophisticated measures are not available or feasible.The development of mixed-donor chimerism (MC) may indicate impending graft failure or disease relapse.The identification of MC early post transplant can assist with prognostication as well as guide potential interventions, which could positively impact the trajectory of the disease course.
Purpose: The primary purpose was to evaluate whether MC is associated with poorer overall survival (OS).
Methodology: Adults with AML or MDS who received an SCT between 1 January 2016 and 1 February 2022 and had at least one donor chimerism measured on day 30 (D30), day 60 (D60), or day 90 (D90) at Juravinski Hospital (Hamilton, ON, Canada) were retrospectively analyzed.Complete chimerism (CC) was defined as ≥95%, whereas MC was defined as ≤95%.All the chimerism measurements were measured using a PowerPlex ® 16 system (Promega) (Hamilton Regional Laboratory Medicine Program, Hamilton, ON).OS was estimated using the Kaplan-Meier method.Log-rank tests were used to compare survival curves.
Results: A total of 143 patients with a median age of 63 years (19-76) were transplanted for AML (n = 105), MDS/AML (n = 20), and MDS (n = 18).The relative proportion of participants with WB CC was similar between D30 (78%) and D90 (77%), with a slight reduction at D60 (74%) in MC.The relative proportion of participants with TC CC increased between D30 and D90, while TC MC decreased.The numbers of patients who improved from MC at D30 to CC at D90 in WB and TC were five and 14, respectively.The median OS was not reached for WB and TC CC at all the measurement time points and was significantly longer for patients at all the time points compared to patients with MC.The D30 WB and TC median OS were 9.1 months and 19 months, respectively.Overall, 55 of 143 (38.5%) patients in the cohort died.OS was significantly different between CC and MC for WB and TC at all three time points (p < 0.025).D30 WB MC was found to be a strong early prognostic indicator (hazard ratio: 2.67) as well as D30 TC MC (hazard ratio: 2.27).Cellular therapy interventions associated with MC included donor lymphocyte infusion (DLI) (n = 7) and a second transplant (6).A total of 6 of 6 (100%) second-transplant patients died, while 6 of 7 (86%) DLI patients were alive.See Tables 1 and 2 and Figure     Background: Flow cytometers are key analyzers in stem cell biomanufacturing, performing both CD34+ enumeration and phenotypic characterization of cell therapy products essential for identity, dosage, viability, and potency evaluation of cell therapy products.This system analyzes individual cells as they are hydrodynamically focused and flow past a laser.Photodetectors collect electronic and optical data from individual cells as they hydrodynamically cross the laser beam to allow for the phenotypic classification of cells based on multiple parameters detected during acquisition.The Canadian Blood Services' (CBS') Stem Cell team currently uses a Beckman Coulter FC500 flow cytometer with a locked StemCXP algorithm for the automated gating of stem cell samples.
Purpose: The aim of this study is to present a structured approach to flow cytometry verification studies through the implementation of the new Beckman Coulter Navios EX flow cytometry system in the CBS' stem cell biomanufacturing environment.
Methodology: Verification studies included examining the accuracy and precision of the Beckman Coulter Navios EX flow cytometers in our environment, including the Stem-kit, the Cyto-Stat triChrome CD45-FITC/CD-19-RD1/CD3-PC5, and the Cyto-Stat tetraChrome CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5, as lab-developed tests.In addition, inter-and intra-instrument parallel studies coupled with a linear regression evaluation have been performed to correlate FC500 to the Navios EX instruments on a variety of stem cell sample types, including mobilized peripheral whole blood, hematopoietic progenitor apheresis cell products, cord blood, bone marrow, and non-mobilized mononuclear cell products.
Results: The installation and operational qualification verification determined that the instruments have been installed according to the manufacturer's recommendations and configured to operate as required by the specifications.Parallel CD34 enumeration scattergrams of different sample types demonstrated strong linear correlations with the following acceptable R 2 values: TNC% viability, 0.9961; CD45% viability, 0.9989; CD34% viability, 0.8327; leukocyte count (×10 3 /µL), 0.9685; viable CD34/µL, 0.995; total CD34/µL, 0.9835.Similarly, phenotyping scatterplots show a close fit of the linear regression trendline with the parallel testing data (R 2 values range from 0.9818 to 0.9987).A comparison to the reference value obtained with StemCXP was used to optimize the lab-developed tests, in particular, the shape of the regions, as in the absence of the StemCXP algorithm, the regions are not auto adjusted to the shape of the target population.

Background:
In severe aplastic anemia (SAA), allogeneic blood and marrow transplantation (BMT) is a curative treatment option for eligible patients.The BMT team is often faced with a clinical conundrum when evaluating patients with concurrent severe infections and poor performance statuses who are referred for transplants.The following case study aims to highlight a successful BMT in a patient with multiple severe infections through a creative multidisciplinary approach.
Purpose: To highlight a successful peripheral blood stem cell transplant in a patient with SAA who was toxic, with multiple refractory concurrent infections, and bed-ridden, with a large nonhealing perianal ulcer restricting him to a prone position.
Case: A 33-year-old male with a diagnosis of SAA versus hypoplastic MDS was referred for a transplant.He had been hospitalized for the previous 4 months because of multiple infections refractory to the treatment.He had a large necrotizing peri-anal and sacral wound, measuring 11 cm × 9.5 cm, secondary to a hemorrhoidectomy performed while he was neutropenic.He was febrile, toxic, bed-ridden, and on daptomycin and meropenem for persistent multiorganism bacteremia with Enterococcus gallinarum and Stenotrophomonas maltophilia.He was also on amphotericin and isavuconazole therapy for a possible invasive fungal pneumonia based on radiological findings.His KPS was 20% (hospitalized and bed-ridden), and he was only able to lie in the prone position.As a lifesaving measure, he was considered for transplant.Because of the diagnostic overlap between SAA and hypoplastic MDS, the chosen conditioning regimen was fludarabine and busulfan (FB2), and GvHD prophylaxis was with anti-thymoglobulin, methotrexate, and cyclosporine.Total body irradiation (TBI) was omitted because of the inability of the patient to lie in the supine position.He underwent a matched-sibling donor transplant using peripheral blood stem cells (PBSCs), with a CD34 cell dose of 8.17 × 10 6 cells/kg of bodyweight.The graft source was PBSCs rather than bone marrow to facilitate rapid engraftment.The infected wound was 11 × 9.5 cm, with 75% slough (images will be shown).The measures to manage the wound were (a) a barrier wipe to protect the periwound and Hydrofera Blue classic applied to the wound bed, (b) a diluted solution of 50% antibacterial MEDIHONEY, (c) hyperbaric oxygen before and after the transplant, (d) broad-spectrum antimicrobials, (e) total parental nutrition, (f) pain management, and (g) aggressive physiotherapy.The outcome was successful, with neutrophil engraftment on day +14 and platelet engraftment on day +31.On day +86, he was transferred to an inpatient rehabilitation centre and subsequently discharged home on day +93.All the antimicrobials were stopped by day +120.The wound healed, and he remains well and independently ambulant, with no graft-versus-host disease.

Conclusion:
A multidisciplinary team approach can be lifesaving in patients with SAA who may be considered as being ineligible for BMT because of their active co-morbidities.
Abstract 23 (Poster): Medication Utilization for the Management of Toxicities Associated with CAR T-Cell Therapy: The Nova Scotia Experience Background and Purpose: Cyclosporine A (CsA) is a calcineurin inhibitor used to prevent graft-versus-host disease post allogeneic stem cell transplant (Allo-SCT).These patients are also at risk of invasive fungal infections and require antifungal prophylaxis.Cyclosporine and posaconazole have a known drug interaction through CYP3A4 yet are often given concurrently.To the best of our knowledge, no studies have described the optimal CsA dose conversion when concurrently changing CsA intravenous (IV) to oral (PO) and IV echinocandins to PO posaconazole.Primary outcome: The proportion of the initial CsA trough levels within the therapeutic range was assessed after CsA IV:PO conversion and the initiation of PO posaconazole, and guiding principles were developed for CsA IV:PO conversion with the concurrent initiation of PO posaconazole.Secondary outcome: The effectiveness of our current CsA therapeutic drug monitoring was evaluated.
Methodology: A retrospective chart review was conducted for 200 patients who underwent Allo-SCT and had concurrent conversion of CsA IV:PO and IV echinocandins to PO posaconazole between 1 July 2019 and 1 November 2021.Cyclosporine trough levels were collected from the initiation of the CsA until discharge from the hospital.Patients were stratified based on the most recent CsA trough level prior to the CsA IV:PO conversion (subtherapeutic, within target range, or supratherapeutic).
Results: Fifty-nine percent of the patients had their first post-conversion CsA trough level within the target range (150-250 µg/L).The average CsA IV:PO conversion was 1:0.73.Patients who were supratherapeutic before the conversion were less successful than patients who were within the target range or subtherapeutic (55.9%, 63.6%, and 60%, respectively).The factors that correlated with less-successful CsA IV:PO conversion were obesity, patient receipt of matched donor stem cells or bone marrow stem cells, and if only one of PTCy and ATG was used in GvHD prophylaxis.
Background: Chimeric-antigen-receptor (CAR) T-cell therapy treatment requires the initial autologous collection of T-cells, which will be genetically reprogrammed via a viral vector to bind to specific cell surface antigens on target cells (CCO, 2023).An initial step in the production of a CAR T-cell therapy product is collecting the target cells from the autologous donor by apheresis.Apheresis collection requires specially trained nursing staff.There is variation in the target cell types for various CAR T-cell products.Tools designed at one centre to support apheresis nurses with collections targeting CD3+ cells needed to be adapted to target mononuclear cell (MNC) counts.These tools were used to train apheresis nurses to estimate the final product volume to attain the target cell count using the interim complete blood count (CBC) on the product.
Purpose: There are minimal tools and literature to guide the apheresis nurse to obtain target products.At our centre, a formula has been used to predict target yields based on interim product CBC results.This method had been used previously to successfully predict collected volumes with products targeting a CD3+ cell count.For products targeting specific MNC counts, this process was revised.
Methodology: The apheresis nurse collects an interim CBC on the product halfway through the collection procedure.The MNC count at the interim is determined from the results.Using the product volume collected at the time of the sampling, the volume of the product required to meet the target count is calculated.Nursing staff use a formula specific to a product target based on MNC or CD3+ cell counts to guide them on how long to continue the procedure.All the apheresis nurses collecting CAR T-cells were experienced stem cell collection nurses who have completed training on the collection policy and completed shifts with a competent preceptor utilizing competency records to track their progress.The nurses experienced in CAR T-cell collection using the previous formula to estimate the product volume for a specific CD3+ target were trained on the new formula to target MNC cells.
Results: With the support of the interim sample results and formula to guide them, apheresis nurses were able to successfully reach target MNC cells in the final product in a similar fashion to products with a CD3+ target.
Conclusion: Many factors affect the final number of target cells in the product.Tools, such as this centre's formulae to estimate the final product volume based on interim product CBC results, help to support the training of apheresis nurses in this area.This unit-based quality improvement project could form the basis of additional studies on product collection variables to attain target cell counts.

Figure 1 .
Figure 1.Event-free survival per central review.Figure shows the Kaplan-Meier estimate of EFS by blinded central review in patients with MTV evaluated.EFS was defined as the time from randomization to the earliest date of disease progression, according to the Lugano classification (Cheson et al.Journal of Clinical Oncology 2014) of new lymphoma therapy, death from any cause, or the best response of the stable disease up to and including the response of the day-150 assessment after randomization, per blinded central review.Tick marks indicate patients who did not meet the criteria for an event and were censored.Axi-cel, axicabtagene ciloleucel; EFS, event-free survival; HR, hazard ratio; MTV, metabolic tumor volume; SOC, standard of care.References: Cheson BD, Fisher RI, Barrington SF et al.Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification.Journal of Clinical Oncology, 32(27):3059-68, 2014.Dean EA, Mhaskar RS, Lu H et al.High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma.Blood Advances, 4(14):3268-3276, 2020.

Figure 1 .
Figure 1.Event-free survival per central review.Figure shows the Kaplan-Meier estimate of EFS by blinded central review in patients with MTV evaluated.EFS was defined as the time from randomization to the earliest date of disease progression, according to the Lugano classification (Cheson et al.Journal of Clinical Oncology 2014) of new lymphoma therapy, death from any cause, or the best response of the stable disease up to and including the response of the day-150 assessment after randomization, per blinded central review.Tick marks indicate patients who did not meet the criteria for an event and were censored.Axi-cel, axicabtagene ciloleucel; EFS, event-free survival; HR, hazard ratio; MTV, metabolic tumor volume; SOC, standard of care.

Figure 1 .
Figure 1.Response rate and duration for consecutive infused patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel in Nova Scotia.PR (partial response) and CR (complete response) per standard PET-CT criteria.Abstract 10 (Poster): Early Experience with Standard-of-Care CAR T-Cell Therapy in Alberta Robert Puckrin, Ahsan Chaudhry, Krista MacAlister, Judith Olesen, Nizar Bahlis, Jan Storek, Kareem Jamani, Adam Bryant, Jason Tay, Douglas Mahoney, Carolyn Owen, Peter Duggan, Douglas Stewart, and Mona Shafey Alberta Blood and Marrow Transplant Program, Foothills Medical Centre, Calgary, AB, Canada Background: CAR T-cell therapy has revolutionized the treatment of hematological malignancies but did not become routinely available in Alberta until a provincial CAR Tcell program opened in Calgary in March 2021.Purpose: To evaluate the early experience and clinical outcomes of standard-of-care CAR T-cell therapy in Alberta.Methodology: This study included all the patients ≥18 years old referred for commercial CAR T-cell therapy before November 2022.Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method.Results:Among 41 referred patients, 29 (71%) were approved for treatment, whereas 12 (29%) were ineligible.Two (7%) patients did not proceed to leukapheresis because of rapid disease progression.Among 27 patients who underwent leukapheresis, 22 (81%) received CAR T-cell infusion, whereas five (19%) did not because of disease progression (n = 3), fatal infection during bridging therapy (n = 1), or manufacturing failure (n = 1).Manufacturing failure occurred in three (11%) patients, necessitating a second attempt,

Figure 1 .
Figure 1.Response rate and duration for consecutive infused patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel in Nova Scotia.PR (partial response) and CR (complete response) per standard PET-CT criteria.
Conclusion: Standard-of-care CAR T-cell therapy in Alberta has a manageable safety profile and favourable efficacy, which mirrors the results of clinical trials and other realworld studies.Further work is needed to optimize the geographic distance to treatment centres and to reduce the risk of drop-out prior to infusion, which represent significant barriers to the successful delivery of CAR T-cell therapy.Curr.Oncol.2024, 31, FOR PEER REVIEW 13 with a median age of 64 years (range: 22-75) who received axicabtagene ciloleucel (n = 14), tisagenlecleucel (n = 7), or brexucabtagene autoleucel (n = 1) for large B-cell lymphoma (n = 20), B-cell acute lymphoblastic leukemia (n = 1), or mantle cell lymphoma (n = 1).Cytokine release syndrome (CRS) occurred in 18 (82%) patients, including one (5%) patient with grade 3 CRS.Neurotoxicity (ICANS) occurred in seven (32%) patients, including two (9%) patients with grade 3 ICANS.One (5%) patient died of non-relapse mortality 12 months after CAR T-cell infusion because of COVID-19 infection.

Figure 1 .
Figure 1.PFS and OS of patients who were (A) intended for CAR T-cell therapy (n = 29) and (B) who received CAR T-cell infusion (n = 22) in Alberta.

Background:
Princess Margaret (PM) is the referral centre for CD19 CAR T-cell therapy (CART) for a large local population and a national referral centre.A better understanding of early CART failure may inform selection criteria.

Figure 1 .
Figure 1.Overall survival from intake date, CAR T-cell therapy vs. no CAR T-cell therapy.

Table 1 .
Summary of all the data collected in the study.Numbers are followed by percentages in parentheses unless otherwise mentioned.

Figure 1 .
Figure 1.Overall survival from intake date, CAR T-cell therapy vs. no CAR T-cell therapy.
1. Conclusion: Mixed-donor chimerism remains a strong prognostic indicator at all stages in first 90 days post SCT.This provides evidence to support further investigation into the beneficial impact of earlier interventions, such as DLI, or novel interventions post SCT.

Figure 1 .
Figure 1.Survival curves for mixed versus complete whole-blood or T-cell chimerisms at day 30, day 60, and day 90.

Figure 1 .
Figure 1.Survival curves for mixed versus complete whole-blood or T-cell chimerisms at day 30, day 60, and day 90.

Table 1 .
Gene expression of pediatric HSCT patients according to NK cell cluster.Cluster 0 (light blue colour) refers to cytotoxic CD56 dim NK cells; Cluster 1 (orange colour) includes classic CD56 bright NK reg cells; Cluster 2 (yellow colour) are Type I interferon-responsive NK reg cells.

Table 1 .
Summary of key metabolites elevated or depressed at cGvHD onset and critical statistical values showing significant differences between control and pathological groups.

Table 1 .
Baseline patient and disease characteristics for patients with relapsed/refractory large B-cell lymphoma treated with axicabtagene ciloleucel in Nova Scotia.

Table 1 .
Patient characteristics in high-risk MM population.

Table 1 .
Comparison between collected patients who proceeded and did not proceed to CAR T-cell infusion.p-Values of 0.04 or less are presented in bold text.

Table 1 .
Cont.Data from 109 Canadian pts with R/R DLBCL who met RE-MIND2 study criteria were included.Seventy-two out of 97 pts (74.2%) enrolled in 2L were considered as being eligible to receive ASCT.Table

Table 1 .
Patient demographics and baseline disease characteristics for patients who received or did not receive ASCT for second-line therapy.

Table 2 .
Summary of ASCT eligibility at the start of second-line therapy and reasons for ASCT ineligibility.