Harmonized Immune Recovery Monitoring after HCT: Evidence & Practical Guidance from the Westhafen Intercontinental Group.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative option for patients with high-risk malignancies and non-malignant disorders. Long-term survival depends on robust immune reconstitution (IR), which governs overall immune homeostasis and risks of infection, graft-versus-host disease, and relapse. However, despite its centrality to post-transplant outcomes, IR is not consistently monitored across transplant centers, limiting ability to generate meaningful, comparable, and translatable data.

Remestemcel-L-rknd (Ryoncil): the first approved cellular therapy for steroid-refractory acute GVHD.

Until recently, the JAK1/2 inhibitor, ruxolitinib (Jakafi), was the only therapy for steroid-refractory acute graft-versus-host disease (SR-aGVHD) approved by the U.S. Food and Drug Administration (FDA) for use in patients older than 12 years.

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).

Understanding Telomere Biology in Hematopoietic Cell Transplantation: A Dynamical Systems Perspective.

Background: T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic cell transplantation (HCT). This process may be modeled as a dynamical system and in such a system, precise telomere length (TL) measurement may reflect the proliferative capacity of donor T cells. TL for different chromosomes span a few orders of magnitude, and different blood cell populations including T cell clones display variable TL; these differences across the cell populations are not represented when examining average leukocyte TL.

Refinement of Day 28 Treatment Response Criteria for Acute GVHD: A Collaboration Study of the JSTCT and MAGIC.

Overall response (OR) that combines complete (CR) and partial responses (PR) at day (D) 28 is the conventional endpoint for acute GVHD trials. Since PR includes heterogeneous clinical presentations, reclassifying PR could produce a better endpoint. Patients in the primary treatment cohort from JSTCT were randomly divided into training and validation sets.

Vascular biomarkers reveal a unique toxicity profile of posttransplant cyclophosphamide: secondary analysis of BMT CTN 0402 and 1202.

Post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis regimens are associated with very low rates of severe acute and chronic GVHD after hematopoietic cell transplant (HCT). However, concerns about cardiac and other organ toxicities persist. This study aimed to compare the vascular biomarker profile of PTCy with other GVHD regimens, including Tacrolimus/Sirolimus (Tac/Sir) and Tacrolimus/Methotrexate (Tac/MTX), to generate hypotheses for toxicity mitigation strategies.

Prediction and Prognostication of Acute Graft-Versus-Host Disease by MAGIC Biomarkers.

Recent advancements in prophylaxis for acute graft-versus-host disease (GVHD) have successfully reduced the incidence of severe cases; however, overall survival rates have not significantly improved, and GVHD continues to be a major cause of mortality. The severity of gastrointestinal (GI) damage is especially critical, as it strongly correlates with treatment failure and non-relapse mortality, but clinical symptoms do not reliably predict peak severity in its early stages. Biomarker-based algorithms, such as the Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm, leverage serum levels of GI GVHD biomarkers (ST2 and REG3α) to quantify intestinal crypt damage, providing more accurate predictions of GVHD outcomes compared to clinical assessments.

Graft-versus-host disease prophylaxis shapes T cell biology and immune reconstitution after hematopoietic cell transplant.

Successful hematopoietic cell transplant requires immunosuppression to prevent graft-versus-host disease (GVHD), a lethal, T-cell-mediated post-transplant complication. The phase 3 BMT CTN 1703 trial demonstrated superior GVHD-free/relapse-free survival for post-transplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis versus tacrolimus/methotrexate (Tac/MTX), but did not improve overall survival. To compare T-cell biology between GVHD prophylaxis regimens, 324 patients were co-enrolled onto BMT CTN 1801 (NCT03959241).

Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndrome.

Background: Donor selection is a key success factor in allogeneic haematopoietic cell transplant (HCT). We evaluated the potential impact of donor leucocyte telomere length (LTL) and LTL shortening in recipients at three-month post-HCT (LTL-3MS) on the two-year HCT outcomes.

Methods: We identified a cohort of 384 HCT recipients for early-stage leukaemia or myelodysplastic syndrome in the Blood and Marrow Transplant Clinical Trial Network protocol#1202 with blood samples collected three-month post-HCT.

Understanding Telomere Biology in Hematopoietic Cell Transplantation: A Dynamical Systems Perspective.

Background: T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic cell transplantation (HCT). This process may be modeled as a dynamical system and in such a system, precise telomere length (TL) measurement may reflect the proliferative capacity of donor T cells. TL for different chromosomes span a few orders of magnitude, and different T cell clones will display variable TL; these differences across the population are not represented when examining average TL.

Reparative immunological consequences of stem cell transplantation as a cellular therapy for refractory Crohn's disease.

Background: Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous haematopoietic stem cell transplantation (SCT) is an emerging therapy for medically refractory CD though the mechanisms through which it circumvents refractory pathophysiology are unknown.

Objective: The objective of this study is to understand how the immune system reconstitutes post-SCT and whether SCT may function as a cellular therapy restoring appropriately responsive immune cell populations from haematopoietic stem cells (HSCs).

F-FLT PET and Blood-based Biomarkers for Identifying Gastrointestinal Graft versus Host Disease after Allogeneic Cell Transplantation.

Purpose To determine whether fluorine 18 (F) fluorothymidine (FLT) PET imaging alone or combined with Mount Sinai Acute GVHD International Consortium (MAGIC) biomarkers could help identify subclinical gastrointestinal graft versus host disease (GI-GVHD) by day 100 following hematopoietic stem cell transplantation (HSCT). Materials and Methods F-FLT PET imaging was analyzed in a prospective pilot study (ClinicalTrials.gov identifier no.

Hematopoietic cell transplant compared with standard care in adolescents and young adults with sickle cell disease.

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation.

Differences in Acute Graft-Versus-Host Disease (GVHD) Severity and Its Outcomes Between Black and White Patients.

Acute graft-versus-host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation (HCT). Although recent advancements in GVHD prophylaxis have resulted in successful HCT across HLA barriers and expanded access to HCT for racial minorities, less is known about how race affects the severity and outcomes of acute GVHD. This study examines differences in the clinical course of acute GVHD and the prognostic value of GVHD biomarkers for Black and White recipients.

Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD.

Acute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model's prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts.

The reparative immunologic consequences of stem cell transplantation as a cellular therapy for refractory Crohn's disease.

Background: Treatment strategies for Crohn's disease (CD) suppress diverse inflammatory pathways but many patients remain refractory to treatment. Autologous hematopoietic stem cell transplantation (SCT) has emerged as a therapy for medically refractory CD. SCT was developed to rescue cancer patients from myelosuppressive chemotherapy but its use for CD and other immune diseases necessitates reimagining SCT as a cellular therapy that restores appropriately responsive immune cell populations from hematopoietic progenitors in the stem cell autograft (i.

Secret disclosure and social relationships in groups.

Personal secrets are a ubiquitous fact of group life, but the conditions under which they are revealed have not been explored. In five studies, we assessed secret disclosure in groups governed by four models of human sociality (Communal Sharing, Equality Matching, Authority Ranking, Market Pricing; Fiske). In Studies 1a and 1b, participants indicated their willingness to disclose secrets in hypothetical groups governed by the models.

Dynamics of cytomegalovirus-specific T-cell recovery in allogeneic hematopoietic cell transplant recipients using a commercially available flow cytometry assay: A pilot study.

Background: Cytomegalovirus-specific T-cell-mediated immunity (CMV-CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo-HCT), but to date, there is no validated measure of CMV immunity for this population.

Methods: In this prospective, observational, pilot study, CMV T-cell responses were evaluated monthly and at onset of graft-versus-host disease (GVHD) or CMV infection in CMV-seropositive allo-HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T-Cell Immunity Panel (CMV-TCIP). The primary endpoint was the time to first positive CMV-TCIP, defined as percentage of interferon-γ-producing CD4+ or CD8+ CMV-specific T cells >0.

The MAGIC algorithm probability predicts treatment response and long-term outcomes to second-line therapy for acute GVHD.

The significance of biomarkers in second-line treatment for acute graft-versus-host disease (GVHD) has not been well characterized. We analyzed clinical data and serum samples at the initiation of second-line systemic treatment of acute GVHD from 167 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC) between 2016 and 2021. Sixty-two patients received ruxolitinib-based therapy, whereas 102 received other systemic agents.

Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD.

Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [REG3α]) when measured at GVHD diagnosis are validated predictors of NRM risk but have never been assessed in the same patients using identical statistical methods. We measured the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts.

Defining and Grading Infections in Clinical Trials Involving Hematopoietic Cell Transplantation: A Report From the BMT CTN Infectious Disease Technical Committee.

The Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) was established in 2001 to conduct large multi-institutional clinical trials addressing important issues towards improving the outcomes of HCT and other cellular therapies. Trials conducted by the network investigating new advances in HCT and cellular therapy not only assess efficacy but require careful capturing and severity assessment of adverse events and toxicities. Adverse infectious events in cancer clinical trials are typically graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE).