Allogeneic bone marrow transplantation remains the most potent curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) due to the graft-versus-tumor effect provided by donor cells. Donor chimerism is utilized early after transplantation to evaluate engraftment and to monitor the persistence of donor hematopoiesis. Literature is conflicting regarding to the prognostic utility of early mixed donor chimerism, chimerism kinetic patterns as well as factors associated with it and we sought to clarify this uncertainty. In this single-centre retrospective analysis, 141 adults aged 18 years of age or older with AML (n=104) and MDS (n=37) who received their first transplant from HLA matched related, matched unrelated or mismatched related (haploidentical) donors between 2016 and 2022 and had at least day 30 chimerism measured were included. Approximately 30% received post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis and 67% of subjects received reduced-intensity conditioning. Chimerism was measured using STR-PCR from unfractionated peripheral blood mononuclear cells (whole blood; WB) and CD3+ (T cell; TC) compartment at each time point. Complete donor chimerism was defined as ≥95% whereas <95% defined as mixed. Competing risk analysis was used to estimate cumulative incidence of relapse with kinetic calculations completed using an increment factor. Kaplan-Meier was used for overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards regression was used to explore prognostic factors for OS and RFS. Both day 30 mixed WB and TC donor chimerism were individually associated with an increased risk of relapse and worse overall and relapse-free survival at days 30, 60 and 90 post-transplant. Day 30 mixed WB was more specific for relapse (86%), while mixed TC was more sensitive (67%). Complete day 30 chimerism had a negative predictive value of 63% and 70% and positive predictive value of 57% and 67% for WB and TC, respectively. Day 30 WB and TC donor chimerism of <88.92% and 89.29% had specificities of 79.17% and 82.19% although sensitivities only approximated 50%. Evaluating the kinetics of chimerism over the first 90 days provided additional information for prognosticating relapse than absolute chimerism values at individual time points in both WB day 30 to 90 [HR, 1.75 (95% CI, 1.04-2.94); p<0.035] and TC day 60 to 90 [HR, 1.32 (95% CI, 1.03, 1.69); p<0.29]. Twice as many patients with complete chimerism developed acute GVHD compared to those with mixed chimerism. Factors that were found to be associated with day 30 mixed TC chimerism were donor source, ATG GVHD prophylaxis, myeloablative conditioning and female sex, while only donor source was associated with mixed WB. Both TC and WB day 30 mixed chimerism were associated with an increased risk of relapse. Early mixed WB and TC chimerism is strongly associated with a worse overall and relapse-free survival. The serial measurement of chimerism early post-transplant for monitoring chimerism kinetics provides additional prognostic information beyond the absolute donor chimerism value at a single time point. Haploidentical stem cell transplants were associated with a lower likelihood of mixed chimerism than other donor sources.

Allogeneic hematopoietic cell transplantation (alloHCT) is the sole curative therapy for myelodysplastic syndrome (MDS). While alloHCT clearly confers a significant survival advantage in high-risk MDS, it is less clear how the disease burden and impact of conditioning intensity impact survival. This review addresses critical issues surrounding this topic, emphasizing the unique cell biology of MDS and the evolving concepts of conditioning intensity compared to other diseases, including acute myeloid leukemia (AML). The review is structured around three interconnected themes. First, it clarifies the varying interpretations of conditioning intensity. Second, it examines the interplay between disease burden at transplant and conditioning intensity in determining outcomes, including a comparative analysis with acute myeloid leukemia (AML) to highlight similarities and differences. Third, it explores the relationship between conditioning regimen intensity and immune reconstitution, particularly focusing on the graft-versus-tumor (GvT) effect and its potential modulation by conditioning intensity. Understanding the stem cell target of conditioning regimens is emphasized, as the persistence of the underlying MDS stem cell necessitates a thorough understanding of this concept for improved therapeutic strategies.

Background: The aim of this study was to evaluate real-world clinical outcomes and transplant-related complications of allogeneic stem cell transplantation (alloSCT) for Hodgkin lymphoma (HL). Methods: This was a single-centre, retrospective analysis of relapsed and refractory (R/R) HL patients who received an alloSCT between 1 January 2016 and 29 February 2024 in Hamilton, Ontario. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease/relapse-free survival (GRFS). Results: Twenty-one patients were identified, with thirteen (62%) pre-treated with programmed death 1 (PD-1) blockade with either nivolumab or pembrolizumab. Seventeen (81%) patients underwent related haploidentical donor transplants, while four (19%) patients received a matched unrelated donor transplant. The 2-year OS and PFS rates were 79% (95% CI: 53–92%) and 63% (95% CI: 37–81%), respectively. Trends towards improved OS, PFS, NRM, and GRFS in PD-1-inhibitor-exposed patients were observed. All PD-1-inhibitor-exposed patients who were in complete remission proceeding to alloSCT remained alive at the last follow-up visit. Among the nine patients in partial remission at the time of alloSCT, three deaths were reported, with a 2-year OS of 61%. Conclusions: Our outcome data of a single-centre, heavily pre-treated cohort of Canadian patients confirm that alloSCT with post-transplant cyclophosphamide-based immunosuppression, which has been associated with improvements in PFS, remains a safe and feasible treatment option for patients with R/R HL in the era of checkpoint inhibitor use.

Background: Chimerism analysis is used in hematopoietic stem cell transplantation (HSCT) to evaluate donor engraftment and assess underlying disease status. Practices vary greatly amongst Canadian transplant centres, and currently, there are no consensus guidelines for testing methodology, time points, cellular source and clinical interventions. Objectives: To review the current chimerism practice patterns for Canadian transplant centres and review current literature Study design: We surveyed members of Cell Therapy and Transplant Canada (CTTC) via a web based application regarding chimerism practices nationwide with approximately half of all transplant centres responding. Results: The majority of centres used similar chimerism laboratory methodologies, though we identified key areas of heterogeneity across transplant centres, namely in the time points for testing and the cellular lineages evaluated. Implications and management of mixed donor chimerism also varied between centres resulting in variability of interventions. Conclusions: Review of current chimerism testing literature highlighted the improving sensitivities of novel testing methods available as well as testing specific cellular lineages to evaluate ongoing donor hematopoiesis. Our survey emphasizes the importance of advocating for a national standard in chimerism testing, and subsequent management based on chimerism results, to better inform clinical practice and to aid in development of prospective research.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2024 Annual Conference. The conference was held on 1–3 May 2024 in beautiful Victoria, British Columbia, at the Victoria Conference Centre, and attracted 293 in-person delegates and five virtual attendees. Several plenary sessions were held on topics such as gene therapy for hemoglobin disorders, optimizing donor selection, graft-versus-host disease (GvHD) strategies, collaborative care, survivorship, graft failure, and CAR-T therapy. Poster authors presented their work during a lively and engaging networking reception on Thursday, 2 May, and oral abstract authors were featured during the oral abstract session in the afternoon of Friday, 3 May 2024. Forty-nine (49) abstracts were selected for presentation as posters and six (6) 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 six (6) abstract authors were invited to give an oral presentation, and the top four (4) poster abstracts were selected to receive an award. All of these were marked as “Award Recipient” within the relevant category. Three abstracts were determined by the peer review panel to be inappropriate for this conference and were not invited to present at the conference, and two authors withdrew their abstract; therefore, five abstract numbers are missing from the list. We congratulate all the 2024 abstract presenters on their research and contributions to the field.