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Abstract: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell-associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Despite the global unrelated donor (URD) registry size, the degree to which URD availability is a transplant barrier is not established. We evaluated the availability of 3,843 URDs requested for 455 diverse adult patients (predominantly with acute leukemia). URDs for non-Europeans were more likely to be domestic and had markedly lower Donor Readiness scores. Of URDs requested for confirmatory HLA-typing (CT) alone (ie, without simultaneous workup), 1,894 of 3,529 (54%) were available. Availability of domestic URDs was 45%. Donor Readiness score was highly predictive of CT availability. More non-European patients (n = 120) than Europeans (n = 335) had >10 URDs requested and <5 available. Of workup requests (after CT or CT-workup), <70% (604/889 [68%]) were available. More non-Europeans had <2 URDs available. URD availability for CT was markedly worse for non-Europeans, with availabilities for African, non-Black Hispanic, and Asian patients being 150/458 (33%), 120/258 (47%), and 119/270 (44%), respectively, with further decrements in URD workup availability. Our data suggest the functional size of the URD pool is much smaller than appreciated, mandating major operational changes for transplant centers and donor registries. Likelihood of donor availability should have a high priority in donor selection. Considering patient ancestry and URD Donor Readiness scores, centers should pursue, and registries permit, simultaneous pursuit of many URDs and abandon futile searches. Patients should be informed about their likelihood of donor availability and alternative options. Finally, although registries should address high URD attrition and speed procurement, use of all HLA-disparate graft types is needed to facilitate timely transplant for all., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Although alternative donors extend transplant access, whether recipient ancestry affects the time to allogeneic transplant is not established. We analyzed the likelihood of clinically significant delays to allograft by patient ancestry in 313 adult patients with acute myelogenous leukemia (AML) who underwent transplantation. Non-European ancestry patients (n = 99) were more likely than Europeans (n = 214) to receive HLA-mismatched donor allografts (45% vs 24%). Overall, the median time from transplant indication to allograft was 127 days (range, 57-1683). In multivariable analysis, non-Europeans had an increased risk of prolonged indication to transplant time >180 days owing to significant delays in indication to consult >90 days and consult to transplant >120 days. Compared with recipients of HLA-matched unrelated donors (URDs), HLA-mismatched adult donor recipients were at an increased risk of delayed indication to transplant, whereas HLA-identical sibling and cord blood recipients were at a lower risk. Subanalysis showed more indication to transplant delays >180 days in non-European (44%) vs European (19%) 8/8 URD recipients. Finally, the pandemic further exacerbated delays for non-Europeans. In summary, although non-European patients with AML are less likely to receive 8/8 URDs as expected, if they do, their transplants are delayed. HLA-identical siblings and cord blood facilitate the fastest transplants regardless of patient ancestry, whereas other adult donor transplants are delayed. Strategies to mitigate referral barriers, hasten donor evaluation, and use all alternative donor sources are critical to ensure timely transplantation for patients with AML., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

For patients in need of allogeneic transplantation who lack an HLA-identical sibling, an 8/8 HLA allele-matched unrelated donor (URD) is a standard alternative. However, delays in URD procurement can adversely impact patient care. Recipient genotype and search assessment (MSKv1.0)-based tools can predict search prognosis for many, but both tools have lower performance in non-European ancestry patients. Using the MSKv1.0 tool, we analyzed searches from 1530 potential allograft recipients (including 863 who underwent transplantation) with the aim of creating an optimized MSKv2.0 search prognosis tool that can classify a URD search as either Good or Poor with a high level of accuracy while also limiting an ambiguous Fair search prognosis regardless of patient ancestry. By MSKv2.0, the 8/8 URD search prognosis distribution was 57% Good, 21% Fair, and 22% Poor in Europeans and 15% Good, 21% Fair, and 63% Poor in non-Europeans. Importantly, compared to MSKv1.0, the likelihood of Fair categorization was reduced to <25% with comparable Fair rates (P = .847) in both European and non-European groups. Moreover, all patients with an MSKv2.0 Good prognosis had an 8/8 URD identified, and almost all of those who underwent transplantation had an 8/8 URD (Europeans, 99%; non-Europeans, 98%; P = .504). The MSKv2.0 tool also was highly accurate at classifying Poor searches, with <10% identifying an 8/8 URD, and almost all patients who underwent transplantation (Europeans, 95%; non-Europeans, 96%) receiving an alternative donor. Using preliminary search results, MSKv2.0 accurately classifies patients by likelihood of 8/8 URD procurement, greatly facilitating triage to 8/8 URD (Good prognosis) or alternative donor (Poor prognosis) transplantations., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57-69]). Of 52 post-CAR-T biopsies evaluated by flow cytometry, 49 (94%) expressed CD19. Subsequent anti-cancer treatment was administered in 135/182 (74%) patients with CAR-T treatment failure. Median OS from the first post-CAR-T treatment was 8 months (95%CI 5.6-11.0). Polatuzumab-, standard chemotherapy-, and lenalidomide-based treatments were the most common approaches after CAR-T. No complete responses (CRs) were observed with conventional chemotherapy, while CR rates exceeding 30% were seen following polatuzumab- or lenalidomide-based therapies. Factors associated with poor OS among patients treated post-CAR-T were pre-CAR-T bulky disease (HR 2.27 [1.10-4.72]), lack of response to CAR-T (2.33 [1.02-5.29]), age >65 years (HR 2.65 [1.49-4.73]) and elevated LDH at post-CAR-T treatment (HR 2.95 [1.61-5.38]). The presence of ≥2 of these factors was associated with inferior OS compared to ≤1 (56% vs. 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Historically, Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with poor outcomes, and allogeneic hematopoietic cell transplantation (allo-HCT) is recommended in first complete remission (CR1). However, in the tyrosine kinase inhibitor (TKI) era, rapid attainment of a complete molecular remission (CMR) is associated with excellent outcomes without allo-HCT, suggesting transplant may not be required for these patients. To test this hypothesis, we retrospectively identified adult patients with Ph+ ALL treated with induction therapy, including TKIs, and attained CMR within 90 days of diagnosis at 5 transplant centers in the United States. We compared outcomes of those who did and did not receive allo-HCT in first remission. We identified 230 patients (allo-HCT: 98; non-HCT: 132). The allo-HCT cohort was younger with better performance status. On multivariable analysis (MVA), allo-HCT was not associated with improved overall survival (adjusted hazard ratio [aHR]: 1.05; 95% CI, 0.63-1.73) or relapse-free survival (aHR: 0.86; 95% CI, 0.54-1.37) compared with non-HCT treatment. Allo-HCT was associated with a lower cumulative incidence of relapse (aHR: 0.32; 95% CI, 0.17-0.62) but higher non-relapse mortality (aHR: 2.59; 95% CI, 1.37-4.89). Propensity score matching analysis confirmed results of MVA. Comparison of reduced-intensity HCT to non-HCT showed no statistically significant difference in any of the above endpoints. In conclusion, adult patients with Ph+ ALL who achieved CMR within 90 days of starting treatment did not derive a survival benefit from allo-HCT in CR1 in this retrospective study., (© 2022 by The American Society of Hematology.)

Vitamin D insufficiency is a potentially modifiable risk factor for poor outcomes in newly diagnosed large B-cell lymphoma (LBCL). However, the role of circulating vitamin D concentrations in relapsed/refractory LBCL treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is currently unknown. This was a single-center, observational study that evaluated the association of pre-CAR-T 25-hydroxyvitamin D (25-OHD) status with 100-day complete response, progression-free survival, overall survival, and CAR-T-related toxicity in 111 adult relapsed/refractory LBCL patients. Vitamin D insufficiency was defined as ≤30 ng/mL in accordance with the Endocrine Society guidelines. The median pre-CAR-T 25-hydroxyvitamin D concentration was 24 ng/mL (interquarile range = 18-34). Vitamin D-insufficient patients (≤30 ng/mL; n = 73 [66%]) were significantly younger than their vitamin D-replete (>30 ng/mL; n = 38 [34%]) counterparts (P= .039). The vitamin D-insufficient cohort was enriched for de novo LBCL as the histological subtype (P= .026) and had a higher proportion of tisagenlecleucel as the CAR-T product (P= .049). There were no other significant differences in the baseline characteristics between the two groups. In vitamin D-insufficient compared to -replete patients, 100-day complete response was 55% versus 76% (P= .029), and 2-year overall survival was 41% versus 71% (P= .061), respectively. In multivariate analysis, vitamin D insufficiency remained significantly associated with 100-day complete response (odds ratio 2.58 [1.05-6.83]; P= .045) and overall survival (hazard ratio 2.24 [1.08-4.66], P= .030). In recipients of tisagenlecleucel, vitamin D insufficiency was associated with significantly lower cell viability of the infused CAR-T product (P= .015). Finally, pretreatment vitamin D insufficiency did not predict for subsequent CAR-T-related toxicity. This is the first report to demonstrate that vitamin D insufficiency is associated with inferior clinical outcomes in CAR-T recipients. Further study into the mechanistic insights of this finding, and the potential role of vitamin D supplementation to optimize CAR-T are warranted., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Stories are powerful in their ability to disseminate information in a meaningful way. We hypothesized that a stem cell donation story library optimized for social media could support the education and recruitment of committed unrelated hematopoietic stem cell donors from needed demographic groups., Study Design and Methods: We developed Why We Swab, a library of stories on stem cell donation (facebook.com/WhyWeSwab; instagram.com/WhyWeSwab; twitter.com/WhyWeSwab), and evaluated its impact across social and traditional media as well as on eligible potential donors' knowledge and attitudes towards donation., Results: As of December 2021, the library included 28 story arcs featuring 45 storytellers from diverse ancestral backgrounds, including 8 donor-recipient stories. Overall, the stories reached >92,000 people across social media. Notably, stories were republished by 18 print/ broadcast media outlets in Canada and by major medical organizations. A series of stories shown to 33 eligible potential donors improved mean total scores on a donation knowledge test (64% to 85%, p < 0.001), reduced mean ambivalence scale scores (3.85 to 2.70, p < 0.001), and improved participants' willingness to register as donors (45% to 73%, p < 0.005). Data are also shown demonstrating that stakeholders valued the library and that its deployment was associated with improved donor recruitment outcomes in Canada., Conclusion: Why We Swab is accessible and relevant to a wide audience, including stem cell donor registries and recruitment organizations seeking to improve their recruitment efforts as well as to blood and organ & tissue donation organizations who can adapt the Why We Swab model to their audiences., (© 2022 AABB.)

Background and Objectives Communities of practice (CoPs) represent effective models to achieve quality outcomes in health care. We report the development and evaluation of a CoP to improve stem cell donor recruitment in Canada. Materials and Methods In September 2017, we invited national stakeholders in stem cell donor recruitment to participate in a Facebook group and regular e-meetings. E-meetings involved speakers and roundtable discussion on topics related to donor recruitment. The Facebook group facilitated sharing of resources. We evaluated stakeholder perspective of the CoP and the impact on recruitment outcomes. Results As of December 2020, the CoP included 382 members who published 243 posts to the Facebook group about patient/donor stories (40%), resources (27%), updates/questions (21%) and recruitment outcomes (12%). In January 2020, we surveyed 44 CoP participants; the majority felt that the Facebook group (86%) and e-meetings (59%) supported the community, and that the CoP fostered collaboration (82%), improved their donor recruitment knowledge (75%) and practice (77%) and improved their ability to recruit needed donors (64%). The launch of the CoP correlated with improved donor recruitment outcomes. In 2016-2017, CoP participants recruited 2918 registrants (46% male; 55.9% non-Caucasian) compared to 4531 registrants in 2018-2019 (52.9% male; 62.7% non-Caucasian). Members of the CoP developed innovative resources to support recruitment efforts and led national campaigns securing coverage in major media outlets. Conclusion We describe the first CoP in stem cell donor recruitment to be formally evaluated. The CoP model may be adopted by donor recruitment organisations, registries and blood banks worldwide to improve recruitment outcomes. HIGHLIGHTS: • A community of practice (CoP) in stem cell donor recruitment was valued by participants and supported efforts to improve recruitment outcomes. • The CoP model may be adopted by donor recruitment organizations, donor registries, and blood banks worldwide to improve recruitment outcomes., (© 2021 International Society of Blood Transfusion.)

Background: Checklists are memory recall tools used across healthcare to improve outcomes. Here, we describe the development and evaluation of checklists to support recruitment of committed allogeneic hematopoietic stem cell donors., Study Design and Methods: Checklists were developed with the following objectives: (1) improve best-practice adherence; (2) reduce errors; and (3) support standardization at stem cell drives. Topics included: recruiting needed donors; securing informed consent; maintaining good-documentation practices; and supervising registration and tissue sample collection. Checklists were iteratively revised with input from stakeholders. We evaluated the checklists by examining recruitment outcomes and errors (i.e., preventing registrants from being listed as donors) pre- (11/2011-8/2016) and post- (9/2016-11/2019) implementation by the Canadian donor recruitment organization Stem Cell Club. Quantitative and qualitative methods were employed to analyze recruiters' perspectives on the checklists., Results: The checklists supported recruitment of donors from needed demographic groups as Stem Cell Club expanded its recruitment effort from 4118 registrants (60% male, 58% non-European) pre-implementation to 10,621 (52% male, 56% non-European) post-implementation. Checklist implementation was associated with a marked reduction in errors (from 13.2% to 1.9%) and a three-fold increase in the match rate of recruited donors (from 0.024% to 0.075%). Qualitative and quantitative analysis of recruiter feedback supported that the checklists' objectives were realized from the recruiter perspective., Discussion: We developed checklists to support donor recruitment and showed that their implementation was valued by recruiters and associated with both reduced errors and improved donor recruitment outcomes. The checklists are relevant to donor recruitment organizations worldwide., (© 2022 AABB.)

Purpose: Tumor-intrinsic features may render large B-cell lymphoma (LBCL) insensitive to CD19-directed chimeric antigen receptor T cells (CAR-T). We hypothesized that TP53 genomic alterations are detrimental to response outcomes in LBCL treated with CD19-CAR-T., Materials and Methods: Patients with LBCL treated with CD19-CAR-T were included. Targeted next-generation sequencing was performed on pre-CAR-T tumor samples in a subset of patients. Response and survival rates by histologic, cytogenetic, and molecular features were assessed. Within a cohort of newly diagnosed LBCL with genomic and transcriptomic profiling, we studied interactions between cellular pathways and TP53 status., Results: We included 153 adults with relapsed or refractory LBCL treated with CD19-CAR-T (axicabtagene ciloleucel [50%], tisagenlecleucel [32%], and lisocabtagene maraleucel [18%]). Outcomes echoed pivotal trials: complete response (CR) rate 54%, median overall survival (OS) 21.1 months (95% CI, 14.8 to not reached), and progression-free survival 6 months (3.4 to 9.7). Histologic and cytogenetic LBCL features were not predictive of CR. In a subset of 82 patients with next-generation sequencing profiling, CR and OS rates were comparable with the unsequenced cohort. TP53 alterations (mutations and/or copy number alterations) were common (37%) and associated with inferior CR and OS rates in univariable and multivariable regression models; the 1-year OS in TP53 -altered LBCL was 44% (95% CI, 29 to 67) versus 76% (65 to 89) in wild-type ( P = .012). Transcriptomic profiling from a separate cohort of patients with newly diagnosed lymphoma (n = 562) demonstrated that TP53 alterations are associated with dysregulation of pathways related to CAR-T-cell cytotoxicity, including interferon and death receptor signaling pathway and reduced CD8 T-cell tumor infiltration., Conclusion: TP53 is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with LBCL treated with CD19-CAR-T. The role of TP53 should be further validated in independent cohorts., Competing Interests: Roni ShouvalConsulting or Advisory Role: Medexus, MyBiotics Michal J. BesserEmployment: Envizion Medical (I)Leadership: Envizion Medical (I)Stock and Other Ownership Interests: Envizion Medical (I)Consulting or Advisory Role: Biological Industries (a Sartorius Company), Gilboa TherapeuticsPatents, Royalties, Other Intellectual Property: Patents at Envizion Medical (I), Royalties at Biological Industries (Inst)Travel, Accommodations, Expenses: Lonza Connie Lee BatleviStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Pfizer, Bristol Myers Squibb, Regeneron, ViatrisHonoraria: DAVA OncologyConsulting or Advisory Role: LifeSci Capital, GLG, Juno Therapeutics, Celgene, Seattle Genetics, Kite, a Gilead company, TG Therapeutics, Karyopharm TherapeuticsResearch Funding: Janssen Biotech (Inst), Novartis (Inst), Epizyme (Inst), Xynomic Pharma (Inst), Bayer (Inst), Roche (Inst), Autolus (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/2778694 Parastoo B. DahiConsulting or Advisory Role: Kite, a Gilead company Sean M. DevlinThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Sergio A. GiraltHonoraria: Celgene, Takeda, Amgen, Jazz Pharmaceuticals, Sanofi,Consulting or Advisory Role: Celgene, Takeda, Sanofi, Jazz Pharmaceuticals, Amgen, Janssen, Actinuum, Bristol Myers Squibb, Johnson & Johnson, PfizerResearch Funding: Celgene (Inst), Miltenyi Biotec, Johnson & Johnson, Amgen, Actinuum, SanofiTravel, Accommodations, Expenses: Celgene, Sanofi, Amgen, Jazz Pharmaceuticals Richard J. LinEmployment: Pfizer (I)Consulting or Advisory Role: Kite/Gilead Gal MarkelEmployment: 4C Biomed, Ella TherapeuticsLeadership: 4C Biomed, Ella TherapeuticsStock and Other Ownership Interests: Purple Biotech, Biond Biologics, Nucleai, Staburo GmbH, Ella Therapeutics, 4C BiomedHonoraria: BMS, MSD, Novartis, Medison, RocheConsulting or Advisory Role: MSD, NovartisSpeakers' Bureau: MSD, BMSResearch Funding: Novartis (Inst), Immunicom (Inst)Patents, Royalties, Other Intellectual Property: Patent on anti-CEACAM1 blocking antibodiesTravel, Accommodations, Expenses: BMS, Novartis, MSD Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, BMS, BeiGene, Incyte, Miltenyi Biotec, Ipsen Craig S. SauterConsulting or Advisory Role: Spectrum Pharmaceuticals, Juno Therapeutics, Sanofi, Gilead Sciences, Novartis¸ Precision BioSciences, Gamida Cell, Karyopharm Therapeutics, GlaxoSmithKline, GenmabResearch Funding: Juno Therapeutics (Inst), Sanofi (Inst), Precision BioSciences (Inst), BMS (Inst), Actinium Pharmaceuticals (Inst)Travel, Accommodations, Expenses: Juno Therapeutics, Sanofi, Gilead Sciences, Novartis Michael ScordoHonoraria: i3 CMEConsulting or Advisory Role: McKinsey & Company, Angiocrine Bioscience, OmerosResearch Funding: Angiocrine Bioscience, Omeros (Inst)Travel, Accommodations, Expenses: Kite/Gilead Gunjan L. ShahResearch Funding: Amgen (Inst), Janssen (Inst) Marcel van den BrinkHonoraria: Seres Therapeutics, Merck, Magenta Therapeutics, WindMIL, Rheos Medicines, Frazier Healthcare Partners, Nektar, Notch Therapeutics, Forty Seven, Priothera, Ceramedix, LyGenesis, Pluto Therapeutics, GlaxoSmithKline, Da Volterra, Novartis (I), Synthekine (I), BeiGene (I)Consulting or Advisory Role: Seres TherapeuticsResearch Funding: Seres TherapeuticsPatents, Royalties, Other Intellectual Property: Dr van den Brink receives royalties from Wolters Kluwer, and he has intellectual property Licensing with Seres Therapeutics and Juno TherapeuticsTravel, Accommodations, Expenses: Rheos MedicinesOther Relationship: DKMSUncompensated Relationships: Seres therapeutics, Notch Therapeutics, Pluto Therapeutics Miguel-Angel PeralesStock and Other Ownership Interests: NexImmuneHonoraria: MorphoSysConsulting or Advisory Role: Incyte, Merck, Servier/Pfizer, NexImmune, Novartis, MolMed, Medigene, Takeda, Nektar, AbbVie, Cidara Therapeutics, Celgene, Kite/Gilead, Bristol Myers Squibb, Omeros, Vor BiopharmaResearch Funding: Incyte (Inst), Miltenyi Biotec (Inst), Novartis (Inst), Kite, a Gilead company (Inst), Nektar (Inst) Maria Lia PalombaStock and Other Ownership Interests: Seres Therapeutics (I)Honoraria: Flagship Biosciences (I), Evelo Therapeutics (I), Jazz Pharmaceuticals (I), Therakos (I), Amgen (I), Merck (I), Seres Therapeutics (I)Consulting or Advisory Role: Flagship Biosciences (I), Novartis (I), Evelo Therapeutics (I), Jazz Pharmaceuticals (I), Therakos (I), Amgen (I), Merck (I), Seres Therapeutics (I), Kite, a Gilead company, Novartis, BeiGene, SynthekineResearch Funding: Seres Therapeutics (I)Patents, Royalties, Other Intellectual Property: Intellectual Property Rights (I), Juno intellectual property rights (Inst)No other potential conflicts of interest were reported.

Allogeneic hematopoietic stem cell transplantation (HCT) is associated with significant morbidity and mortality. Elevated pre-transplant ferritin level (ferritin Pre-HCT ) is reported to be associated with increased mortality following HCT. The present study attempted to determine whether post-transplant ferritin level (ferritin Post-HCT ) is associated with outcomes post-HCT, especially in the subgroups which developed acute or chronic graft-versus-host disease (GVHD). Out of 229 patients with serum ferritin level measured post-HCT, median ferritin Post-HCT was 2178 ng/mL. Patients were stratified into low- or high-risk groups using recursive partitioning, based on ferritin Post-HCT (≤ 3169 vs > 3169 ng/mL) and ferritin Pre-HCT (≤ 669 vs > 669 ng/mL). Compared to the low ferritin Post-HCT group, the high ferritin Post-HCT group had lower 3-year overall survival (OS) (40.0% vs 66.7%, p < 0.001) and higher non-relapse mortality (NRM) (48.6% vs 17.8%, p < 0.001), but no difference in relapse (10.5% vs 19.7%, p = 0.079). Multivariate analysis confirmed ferritin Post-HCT as an independent prognostic factor for OS (p = 0.001, HR = 2.323) and NRM (p < 0.001, HR = 3.905). However, ferritin Pre-HCT did not stratify well for OS or NRM. Ferritin Post-HCT was also found to be an independent prognostic marker for OS and NRM in the subgroups which developed GVHD. In our cohort, high ferritin Post-HCT levels were significantly associated with decreased OS and increased NRM independent of ferritin Pre-HCT or GVHD. Additional studies including larger sample sizes and prospective investigation are warranted to clarify the prognostic significance and pathophysiology of pre- and post-transplant hyperferritinemia.

Background: Diagrams which allow potential unrelated stem cell donors to visualize the stem cell collection process were hypothesized to support the recruitment and education of committed stem cell donors., Study Design and Methods: A series of bone marrow and peripheral blood stem cell collection procedure diagrams were developed, featuring young adult male donors of varied ethnic backgrounds. Post-implementation, surveys were conducted to evaluate stakeholder perspective on the diagrams' utility. A quality improvement project was conducted at five stem cell drives from 2017 to 2018 at which recruiters did or did not show the diagrams to potential donors. Following the drives, registrants were invited to complete a survey exploring their experience, knowledge and attitude towards donation., Results: The diagrams were implemented in Canada in 07/2016. Of 293 participating registrants (24·7% non-Caucasian males) recruited at five drives between 2017 and 2018, 76% (n = 197) were shown the diagrams. Participants who were shown the diagrams were significantly more likely to report that the recruiters appeared very knowledgeable (89% vs. 76%, P = 0·019) and to report improved self-reported knowledge of stem cell donation (P = 0·010) compared to participants not shown the diagram. Data are also shown demonstrating that stakeholders in donor recruitment used and valued the diagrams and that use of the diagrams was associated with improved donor recruitment outcomes in Canada., Conclusion: This report is the first evaluation of stem cell collection diagrams in the literature. The diagrams are relevant to donor registries, recruitment organizations and transplant centres worldwide, and their use may support efforts to educate and recruit committed, ethnically diverse donors., (© 2020 International Society of Blood Transfusion.)

Patients with a variety of blood, immune, and metabolic disorders may require an allogeneic hematopoietic stem cell transplant as part of their treatment. However, over 70% of these patients do not have a matched sibling donor and require an alternative donor, such as a matched unrelated donor. We present a multi-part story of a Canadian stem cell recipient who underwent transplantation for treatment of refractory chronic myelogenous leukemia, and the matched unrelated donor who saved his life. The story segments feature excerpts from interviews with the donor and the recipient, along with representative images of both storytellers. The excerpts were optimized for publication on social media and were arranged to build a story arc that parallels the journey of the donor and recipient together. This donor-recipient story may serve as a resource to help raise awareness about stem cell donation and to encourage eligible individuals to register as donors. The story is one of several developed by Why We Swab, a library of stories in stem cell donation in Canada (Facebook, Twitter, and Instagram; @WhyWeSwab) to support the recruitment of committed unrelated donors.

Background: Recruitment of committed unrelated hematopoietic stem cell donors from the most-needed demographics remains a challenge for donor recruitment organizations worldwide. Multimedia resources are gaining attention as a modality to support recruitment efforts; however, there is a lack of guidance for the development of such tools. This qualitative study explores the perspectives of eligible stem cell donors on an educational whiteboard video about stem cell donation, generating insights into how whiteboard videos and related multimedia may be optimized for donor recruitment., Study Design and Methods: Eight semistructured focus groups were conducted with 38 potential donors from the most-needed demographics (young, male, and non-Caucasian) after they had watched a 3.5-minute whiteboard video explaining key concepts in stem cell donation (https://youtu.be/V4fVBtxnWfM). Constructivist grounded theory was used to identify themes and to develop a framework for understanding participants' preferred features of recruitment multimedia., Results: Participants identified a range of features contributing to the effectiveness of recruitment multimedia, adding that the whiteboard video is an effective, integrated, and readily accessible format for supporting donor recruitment. Topics that participants felt are important to address include knowledge gaps regarding donation procedures, concerns about donor safety, and the particular need for specific donor demographics. Suggested avenues for improvement include the addition of donor/recipient/patient personal experiences, attention-grabbing hooks, and a call to action including opportunities for further learning., Conclusions: Several considerations were generated to inform the development of future multimedia for donor education/recruitment and are relevant to donor recruitment organizations worldwide., (© 2020 AABB.)

Salvage options for patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) include inotuzumab ozogamicin (InO), a recombinant, humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. However, the benefit of InO in patients with dim CD22 expression remains unclear. We present a case of a patient with B-ALL who responded to InO despite only dim surface expression of CD22 by flow cytometry, achieving a survival benefit concordant with that reported in the literature and maintaining a good quality of life as a transfusion-independent outpatient. Our observation has broad relevance to clinicians who manage patients with B-ALL who are candidates for InO.

Objective/background: Patients in need of hematopoietic stem cell transplantation often cannot find a suitable HLA-matched donor in their families and rely on unrelated donors. Individuals can register with their country's donor registry either online or at a stem cell drive by providing consent and a tissue sample for typing., Methods: Stem Cell Club is a donor recruitment organization in Canada that recruits Canadians as stem cell donors. This article outlines the Stem Cell Club's protocol for donor recruitment at stem cell drives including five core components: prescreening, informed consent, registration, tissue sample collection, and reconciliation., Results: At stem cell drives, recruiters approach individuals from the most-needed demographic groups, catch their attention, explain the purpose of the drive, and prescreen them to ensure eligibility. Recruiters then secure informed consent, educating registrants about the stem cell donation process, the risks involved, the right to withdraw, and donor-patient anonymity. Recruiters subsequently ask registrants to register by providing their contact/demographic information, completing a health questionnaire, and signing a consent form. Recruiters also guide registrants to provide a tissue sample (e.g., buccal swab) for typing. Finally, recruiters reconcile completed registration kits and prepare them for shipment to the donor registry. Data are presented demonstrating the effectiveness of stem cell drives employing this protocol on recruitment of the most-needed donor demographics and of quality donors., Conclusion: This protocol incorporates best practices for unrelated donor recruitment. It is relevant to donor recruitment organizations worldwide seeking to improve their recruitment efforts and standardize registrant experience., Competing Interests: Declaration of Competing Interest D.A. is a paid medical consultant with Canadian Blood Services (CBS). W.F. receives grant funding from CBS. H.M. declares no conflicts of interest., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Whiteboard videos are a popular video format, allowing viewers to see drawings of concepts alongside explanatory text and speech. We hypothesized that whiteboard videos could support the education and recruitment of unrelated stem cell donors in Canada. A series of 5 sharable whiteboard videos about stem cell donation was produced and posted online in September 2018, including 1 full-length video (https://youtu.be/V4fVBtxnWfM) and 4 shorter videos titled "What Is Stem Cell Transplantation?" "How Does the Matching Process Work?" "How Are Stem Cells Donated?" and "How Can I Register as a Stem Cell Donor?" In the videos, metaphorical interpretations of stem cells as factories and genetic markers as barcode labels are employed to communicate complex concepts. The particular need for young, male, and ethnically diverse donors is reflected in the characters portrayed. Surveys demonstrated the videos (1) were used and valued by stakeholders in donor recruitment and (2) significantly improved objective and self-reported knowledge about stem cell donation and reduced donation-related ambivalence among viewers from the most-needed donor demographics. Use of the whiteboard videos was also associated with improved donor recruitment outcomes in Canada. Our work is relevant to donor registries and recruitment organizations worldwide that seek to improve their recruitment efforts., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: Worldwide, tobacco smoke is still the leading cause of preventable morbidity and mortality. Many smokers develop chronic smoking-related conditions that require emergency department (ED) visits. However, best practices for ED smoking cessation counselling are still unclear., Methods: A randomized controlled trial was conducted to determine whether an "ask, advise, and refer" approach increases 12-month, 30-day quit rates in the stable adult ED smoking population compared to usual care. Patients in the intervention group were referred to a community counselling service that offers a quitline, a text-based program, and a Web-based program. Longitudinal intention-to-treat analyses were performed., Results: From November 2011 to March 2013, 1,295 patients were enrolled from one academic tertiary care ED. Six hundred thirty-five were allocated to usual care, and 660 were allocated to intervention. Follow-up data were available for 70% of all patients at 12 months. There was no statistically significant difference in 12-month, 30-day quit rates between the two groups. However, there was a trend towards higher 7-day quit attempts, 7-day quit rates, and 30-day quit rates at 3, 6, and 12 months in the intervention group., Conclusion: In this study, there was a trend towards increased smoking cessation following referral to a community counselling service. There was no statistically significant difference. However, if ED smoking cessation efforts were to provide even a small positive effect, such an intervention may have a significant public health impact given the extensive reach of emergency physicians.

Background: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors., Study Design and Methods: The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada., Results: To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality., Conclusion: The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world., (© 2017 AABB.)

Oncologic immunotherapies use a patient's immune response to eliminate tumor cells by modulation of immune checkpoints, including programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) proteins. Immune-mediated sequelae, including interstitial nephritis, have been reported; however, glomerular disease appears rare. We describe 2 cases of nephrotic syndrome in patients treated with these agents. Patient 1 received the anti-PD-1 antibody pembrolizumab for Hodgkin lymphoma. Following his second dose, he developed nephrotic syndrome and acute kidney injury. Biopsy showed diffuse foot-process effacement consistent with minimal change disease and findings of acute tubular injury. Pembrolizumab therapy cessation and corticosteroid treatment yielded improvement in proteinuria and acute kidney injury. Patient 2 received the CTLA-4 antibody ipilimumab for melanoma. He developed nephrotic syndrome with biopsy changes consistent with minimal change disease. Ipilimumab therapy was stopped and proteinuria resolved following corticosteroid treatment. Ipilimumab rechallenge caused relapse of nephrotic-range proteinuria. These cases suggest an association between therapeutic immune activation and the development of nephrotic syndrome. Given the increasing prevalence of oncologic immunotherapies, monitoring patients for renal sequelae is warranted., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Globally, tobacco smoke is the leading cause of preventable deaths. Smoking cessation counselling services are widely available in Canada. In British Columbia, our government-funded smoking cessation service offers counselling via phone, text, or email. In this study, we sought to determine whether age, gender, or motivation to quit affect a patient's choice of service modality. We included all adults ≥ 18 years who had used tobacco within 30 days prior to their Emergency Department (ED) visit and who chose to receive phone, text, or email counselling services from November 2011-February 2013 at Vancouver General Hospital as part of a randomized-controlled trial (ClinicalTrials.gov, NCT0145437). A one-way ANOVA was used to compare the mean age of patients in each group. Chi-squared tests of independence were used to determine if gender or motivation to quit were associated with modality selection. In total, 368 patients were included. The average age was 41.7 years and 67% were female. In our study, 44% chose phone, 17% chose text, and 40% chose email services. The average age for patients preferring text services (mean = 33.6 years) was significantly lower than both the email (mean = 41.3 years) and phone (mean = 45.1 years) groups ( p  < 0.001). Gender and motivation to quit were not associated with service modality choice. Over 80% of ED smokers who accepted a referral to counselling services chose the phone or email modality. The lesser chosen text modality was more popular with younger patients. With further research, smoking cessation counselling services can refine their programs to meet the needs of the population they serve.