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.

The MAGIC Composite Response: A Novel Endpoint Integrating Clinical and Biomarker Parameters for Acute GVHD.

Changes in the clinical symptoms of acute graft versus host disease (GVHD) are currently used to assess responses to treatment. The MAGIC consortium has recently shown that the integration of serum biomarkers with clinical symptoms at the onset of treatment in a MAGIC Composite Score (MCS) more accurately predicts response to treatment and 6-month non-relapse mortality (NRM) than clinical symptoms alone. In this study we evaluated whether the integration of serum biomarkers and clinical symptoms on day 28 (D28) would also better predict NRM than clinical response only (CRO).

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 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.

Matched Unrelated Donor Hematopoietic Cell Transplantation: Increased Usage and Improvements in Clinical Outcomes in Canada.

In allogeneic hematopoietic cell transplantation (HCT), a minority of patients have access to a suitable human leukocyte antigen (HLA)-matched related donor (MRD). To fill this gap, matched unrelated donors (MUDs) are an increasingly selected donor source. Usage and outcomes after MUD HCT for Canada are not described.

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.

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.

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.

Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide.

Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers.

Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT.

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.

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-Based Cohort Study.

Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada.

Letermovir prophylaxis for cytomegalovirus reactivation in allogeneic hematopoietic cell transplant recipients: Single center Canadian data.

Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes.

Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC).

Propensity Score Matching Analysis Comparing the Efficacy and Steroid Tapering Benefit of Extracorporeal Photopheresis to Best Available Therapy in Third-Line or Beyond Treatment for Chronic GvHD.

Graft-versus host disease (GVHD) is one of the major limitations to allogeneic hematopoietic stem cell transplantation (HCT). Although corticosteroids with calcineurin inhibitors are established first line-therapy for chronic graft-versus-host disease (cGVHD), approximately one-half of cGVHD patients are refractory to corticosteroid therapy. The goal of the present study was to compare treatment outcomes of patients treated with extracorporeal photopheresis (ECP) and best available therapy (BAT) as third-line or beyond treatment for cGVHD.

Single centre retrospective analysis of extracorporeal photopheresis (ECP) therapy in patients heavily pre-treated for chronic graft-versus-host disease (cGvHD) with steroid failure.

Background: Extracorporeal photopheresis (ECP) is recommended as a second- or later-line therapy for chronic GvHD (cGvHD). Benefits include reasonable response with avoidance of intense systemic immunosuppression, which can translate into lowering the risk of systemic toxicity and opportunistic infection.

Methods: We evaluated 75 patients treated with ECP for cGvHD from 2007 to 2021 at Princess Margaret Cancer Centre, and analyzed overall response rate (ORR) and clinical benefit (CB) at 3, 6 and 12 months plus other long-term treatment outcomes.