A decade of experience using ATG and PTCy for graft-versus-host disease prophylaxis in matched unrelated donor allogeneic haematopoietic cell transplantation.

Anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) are both effective drugs for graft-versus-host disease (GvHD) prophylaxis, but their combined use remains underexplored. We conducted a retrospective analysis of 582 patients with haematological malignancies who underwent unrelated donor transplantation with Status GvHD prophylaxis consisting of low-dose ATG (2 mg/kg) and PTCy over a 10-year period. The median time to neutrophil and platelet engraftment was 18 days (95% CI, 17-19) and 20 days (95% CI, 19-21) respectively.

Impact of graft-versus-host disease prophylaxis on second primary malignancies after allogeneic haematopoietic stem cell transplantation.

Second primary malignancies (SPMs) are a well-recognized late complication of allogeneic haematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) combination on the incidence of SPMs, compared to other graft-versus-host disease (GvHD) prophylactic regimens. Among 1418 evaluable patients with a median follow-up of 6125 person-years, 138 patients developed an SPM.

Effect of Anti-Thymocyte Globulin and Post-Transplant Cyclophosphamide on Graft-Versus-Host Disease Outcomes in Female Donor-to-Male Recipient Matched Unrelated Donor Allogeneic Stem Cell Transplantation for Acute Leukemia.

Female-to-male (F→M) sex-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is known to increase the risk of graft-versus-host disease (GVHD). We evaluated the impact of donor-recipient sex mismatch on GVHD incidence and assessed the efficacy of combined low-dose antithymocyte globulin (ATG) (2mg/kg) and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis compared to calcineurin inhibitor-methotrexate/mycophenolate mofetil (CNI-MTX/MMF). We retrospectively analyzed 861 HSCT recipients, with acute myeloid leukemia as the predominant indication (82%).

Conditioning Regimens for Second Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Primary Graft Failure.

Primary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). The optimal conditioning strategies for salvage HSCT in PGF remain undefined. We retrospectively analyzed the outcomes of 19 patients with PGF who underwent a second HSCT between 2017 and 2024.

Association of Cyclosporine Exposure Post-Allogeneic Hematopoietic Cell Transplant With Graft Failure and Relapse Risk in Hematological Malignancies.

Background: Allogeneic hematopoietic cell transplantation (HCT) is a cornerstone in the treatment of many high-risk hematological malignancies. Calcineurin inhibitors (CNIs), essential components of GVHD prophylaxis, require careful monitoring of levels to optimize outcomes. This study evaluated the association between cyclosporine (CsA) exposure during the first 90 days post-HCT and key transplant outcomes.

Prolonged length of stay in high-risk patients undergoing allogeneic stem cell transplantation: a call to action for addressing healthcare challenges.

Allogeneic hematopoietic stem-cell transplantation (allo-HCT) is a potentially curative treatment for hematological diseases, but the prolonged length of stay (LOS) post-transplant remains a significant challenge. This retrospective cohort study analyzed 977 patients undergoing allo-HCT at Princess Margaret Cancer Centre between 2017 and 2022 to identify predictors of prolonged LOS and their impact on overall survival (OS) and non-relapse mortality (NRM). The median LOS within the first year was 37 days (range: 15-340).

Impact of Conditioning Intensity on Survival in Adult Patients (< 65 Years) With Acute Myeloid Leukemia Receiving Antithymocyte Globulin and Post-Transplantation Cyclophosphamide Based GVHD Prophylaxis.

Introduction: Myeloablative conditioning (MAC) for acute myeloid leukemia (AML) improves disease control by reducing relapse risk but is associated with higher non-relapse mortality (NRM). Reduced-intensity conditioning (RIC) aims to minimize toxicity but raises concerns about higher relapse rates. This study evaluates the impact of RIC versus MAC in AML patients under 65 years receiving GVHD prophylaxis with antithymocyte globulin, post-transplant cyclophosphamide, and cyclosporine.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Myelodysplastic/Myeloproliferative Overlap Neoplasms.

Myelodysplastic/myeloproliferative overlap neoplasms (MDS/MPN) are rare hematological malignancies. We analyzed the outcomes of 75 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for MDS/MPN. Graft-versus-host disease (GvHD) prophylaxis included post-transplantation cyclophosphamide (PTCy) in 71% of patients, with 44 (59%) receiving a combination of anti-thymocyte globulin (ATG) and PTCy.

Exploring the impact of opioid use on outcomes in allogeneic hematopoietic stem cell transplantation.

Introduction: Hematological malignancies and allogeneic hematopoietic cell transplantation (alloHCT) often necessitate the use of opioids due to significant pain. This study aimed to investigate the impact of opioid use on the clinical outcomes of patients undergoing alloHCT.

Methods: A retrospective cohort study was conducted by merging data from our local transplant database with anonymized pharmacy records obtained from the Institute for Clinical Evaluative Sciences (ICES).

Exploring Outcomes by Ethnicity in Allogeneic Hematopoietic Cell Transplantation.

Background: Clinical outcome disparities among racial and ethnic groups have been described following allogeneic hematopoietic cell transplantation (HCT). This study investigated the impact of race and ethnicity on HCT outcomes in a multi-ethnic single-center population.

Methods: We analyzed outcomes of 709 allogeneic HCT patients, stratified by racial and ethnic groups, who underwent allogeneic HCT between January 2018 and April 2022.

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on Clinical Outcomes in Allogeneic Hematopoietic Cell Transplantation: Does Speeding Up Neutrophil Engraftment Make a Difference?

Background: Despite decades of post-allogeneic hematopoietic cell transplantation (HCT) growth factor utilization, its role remains undefined, leading to ongoing debates and research. The theoretical impacts of growth factors have been challenged in numerous studies.

Methods: In this retrospective cohort study conducted at the Princess Margaret Cancer Centre, we analyzed the clinical outcomes of 509 patients who underwent allogeneic HCT between May 1, 2019, and May 31, 2022.

Cell therapy with human IL-10-producing ILC2s limits xenogeneic graft-versus-host disease by inhibiting pathogenic T cell responses.

Interleukin-10 (IL-10)-producing group 2 innate lymphoid cells (ILC2) regulate inflammatory immune responses, yet their therapeutic potential remains largely unexplored. Here, we demonstrate that cell therapy with human ILC2 inhibits pathogenic T cell responses in humanized mouse models of graft-versus-host disease (GVHD), resulting in reduced GVHD severity and improved overall survival without limiting the graft-versus-leukemia effect. ILC2 conferred superior protection from GVHD than IL-10 ILC2s, and blocking IL-10 and IL-4 abrogated ILC2 protective effects, indicating that these cytokines are important for the protective effects of ILC2.

Single cell profiling of hematopoietic stem cell transplant recipients reveals TGF-β1 and IL-2 confer immunoregulatory functions to NK cells.

Natural killer (NK) cell activity is influenced by cytokines and microenvironment factors, resulting in remarkably diverse functions, by contributing to inflammatory responses or serving as rheostats of adaptive immunity. Using single cell RNA sequencing (scRNA-seq), we identified a CD56NK cell population associated with hematopoietic stem cell transplant recipients protected from acute graft-versus-host disease (GVHD). We further define a role for the combination of interleukin-2 (IL-2) and transforming growth factor β1 (TGF-β1) in promoting a regulatory phenotype in NK cells.

PTCy-based graft-versus-host disease prophylaxis for matched sibling donor allogeneic hematopoietic cell transplantation.

Posttransplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GVHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear. We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into 4 groups: group I (calcineurin inhibitor [CNI] + methotrexate [MTX] or mycophenolate mofetil [MMF]), group II (CNI + MTX or MMF + antithymocyte globulin [ATG]), group III (PTCy + ATG + CNI), and group IV (PTCy + CNI + MMF).

Letermovir as secondary prophylaxis of cytomegalovirus infection after allogeneic hematopoietic cell transplantation: A single center experience.

Letermovir, a novel anti-cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high-risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high-risk patients.

Incidence of venous thromboembolic disease and risk of bleeding in critically ill patients with hematologic malignancies: A retrospective study.

Objective: Our objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM).

Design: Retrospective cohort study (2014-2022).

Setting: Medic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center.

Impact of cytomegalovirus (CMV) seroconversion pre-allogeneic hematopoietic cell transplantation on posttransplant outcomes.

Cytomegalovirus (CMV) reactivation post-allogeneic hematopoietic cell transplantation (post-alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre-alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis.

Treosulfan- Versus Busulfan-based Conditioning in Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Single-center Retrospective Propensity Score-matched Cohort Study.

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia at Princess Margaret Hospital, Toronto, from 2015 to 2022.

Cell Therapy Transplant Canada (CTTC) Consensus-Based Guideline 2024 for Management and Treatment of Chronic Graft-Versus-Host Disease and Future Directions for Development.

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD.

Real-world experience with ruxolitinib therapy for steroid-refractory acute graft versus host disease.

Acute graft versus host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplant (HCT) and is associated with significant morbidity and mortality. Steroid refractory aGVHD (SR-aGVHD) carries a particularly grim prognosis. Ruxolitinib has shown promise for treatment of SR-aGVHD in a phase 3 trial; however, safety and efficacy data outside of the clinical trial setting is lacking.

Dual T cell depletion for graft versus host disease prevention in peripheral blood haploidentical hematopoietic cell transplantation for adults with hematological malignancies.

The ideal immunosuppressive agents to complement post-transplant cyclophosphamide (PTCy) in PBSC-based haploidentical hematopoietic cell transplantation (haplo-HCT) remain debated. This study looks at our experience with ATG-PTCy-Cyclosporine (CsA) prophylaxis in PB haplo-HCT since 2015. Between October 2015 and December 2021, 157 adults underwent haploidentical hematopoietic cell transplantation (haplo-HCT) using a GVHD prophylaxis regimen comprising rabbit-ATG, PTCy, and CsA.

Flow cytometry-based measurable residual disease (MRD) analysis identifies AML patients who may benefit from allogeneic hematopoietic stem cell transplantation.

Measurable residual disease (MRD) monitoring independently predicts long-term outcomes in patients with acute myeloid leukemia (AML). Of the various modalities available, multiparameter flow cytometry-based MRD analysis is widely used and relevant for patients without molecular targets. In the transplant (HCT) setting, the presence of MRD pre-HCT is associated with adverse outcomes.