Relationship between donor source, pre-transplant measurable residual disease, and outcome after allografting for adults with acute myeloid leukemia.

Lack of HLA-matched related/unrelated donor remains a barrier to allogeneic hematopoietic cell transplantation (HCT) for adult acute myeloid leukemia (AML), with ongoing uncertainty about optimal donor type if more than one alternative donor is available. To assess the relationship between donor type, pre-HCT measurable residual disease (MRD), and post-HCT outcomes, we retrospectively analyzed 1265 myelodysplastic neoplasm (MDS)/AML and AML patients allografted in first or second remission with an HLA-matched sibling (MSD) or unrelated donor (MUD), HLA-mismatched unrelated donor (MMD), an HLA-haploidentical donor, or umbilical cord blood (UCB) at a single institution. Relapse risk was non-significantly higher after HLA-haploidentical and lower after UCB HCT.

Relationship Between Age, Conditioning Intensity, and Outcome After Allografting in Adults Age ≥60 Years with AML.

Methodological advancements now allow older adults with AML to receive allografts although conflicting data exist regarding relative outcomes across age groups and benefits of different conditioning intensities. We retrospectively analyzed 495 adults aged 60-64 (n = 184), 65-69 (n = 189), or ≥ 70 (n = 122) who underwent allogeneic HCT for AML in remission at our institution from 2006 to 2023. There were no significant differences in relapse or relapse-free survival (RFS) among the 3 age cohorts after multivariable adjustment.

Measurable Residual Disease as Predictor of Post-Day +100 Relapses Following Allografting in Adult AML.

Measurable residual disease (MRD) by multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) identifies patients at high risk of acute myeloid leukemia (AML) relapse, often occurring early after allografting. To examine the role of MFC MRD testing for the prediction of later relapses, we examined 935 adults with AML or myelodysplastic neoplasm (MDS)/AML transplanted in first or second morphologic remission who underwent bone marrow restaging studies between day 70 and 100 post-HCT and were alive and without relapse by day +100. Of these 136 (15%) had MRD before HCT, whereas only 11 (1%) had MRD at day +70-100.

Relationship between morphologic remission with or without hematologic recovery and outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia.

Outcomes of adults with AML after allografting vary widely. While numerous covariates have been associated with relapse, non-relapse mortality (NRM), and/or shorter survival, the impact of incomplete blood count recovery before transplantation has remained unclear. To address this uncertainty, we examined all adults with AML or MDS/AML who received an allograft in first or second remission between 2006 and 2023 at a single institution.

At-Labeled Anti-CD45 Antibody as a Nonmyeloablative Conditioning for Canine DLA-Haploidentical Stem Cell Transplantation.

The α-emitter At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the At-labeled anti-CD45 monoclonal antibody (mAb) At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen-haploidentical hematopoietic cell transplantation. Seventeen healthy dogs were injected with either a 0.

Outcomes of patients undergoing third hematopoietic cell transplantation for hematologic malignancies.

With advancements in novel therapeutics, it is unclear whether third hematopoietic cell transplantation (HCT3) has a place in the treatment of recurrent hematopoietic malignancies. We evaluated patients with hematologic malignancies who underwent HCT3 between 2000-2020. Nine patients, with a median age of 18 (9-68) years at HCT3 with acute myelogenous leukemia (n = 5), acute lymphoblastic leukemia (n = 2), myelodysplastic syndrome (n = 1), or undifferentiated acute leukemia (n = 1), were identified.

Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Adult Acute Myeloid Leukemia: Outcomes and Prognostic Factors.

Second allogeneic hematopoietic cell transplantation (HCT2) is potentially curative for adults with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS)/AML experiencing relapse after a first allograft (HCT1), but prognostic factors for outcomes are poorly characterized. To provide a detailed analysis of HCT2 outcomes and associated prognostic factors in a large single-center cohort, with a focus on identifying predictors of relapse and nonrelapse mortality (NRM), we studied adults ≥18 years who underwent HCT2 at a single institution between April 2006 and June 2022 for relapsed AML (n = 73) or MDS/AML (n = 8). With a median follow-up among survivors of 74.

Intensive Reinduction Chemotherapy Followed by Early Allogeneic Hematopoietic Cell Transplantation for Relapsed/Refractory High-Grade Myeloid Neoplasms.

Outcomes for adults with relapsed/refractory (R/R) high-grade myeloid neoplasms remain poor, with allogeneic hematopoietic cell transplantation (HCT) the sole therapy likely to result in cure. We conducted the present study to determine the feasibility of early HCT-within 60 days of beginning reinduction chemotherapy-to see whether getting patients to HCT in an expeditious manner would expand the number of patients being offered this curative option. In this proof-of-principle feasibility study, we included adults age 18 to 75 years with R/R myeloid malignancies with ≥10% blood/marrow blasts at diagnosis who were eligible for a reduced-intensity HCT.

Impact of socioeconomic disparities on outcomes in adults undergoing allogeneic hematopoietic cell transplantation for acute myeloid leukemia.

Racial and socioeconomic disparities impact outcomes after chemotherapy and limit access to allogeneic hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML), yet studies have yielded mixed results on the influence of disparities on post-HCT outcomes. Therefore, we studied 1024 adults with AML who underwent allogeneic HCT between 5/2006 and 10/2021 at a single large university-affiliated cancer center. Collected data included non-biologic and demographic characteristics (including race/ethnicity, marital status, distance traveled, and household size), transplant- and disease-related characteristics, and area-level and individual-level socioeconomic factors (i.

Relative prognostic value of flow cytometric measurable residual disease before allogeneic hematopoietic cell transplantation for adults with MDS/AML or AML.

Multiparameter flow cytometry (MFC) measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) independently predicts poor outcomes in acute myeloid leukemia (AML). Conversely, its prognostic value in the newly defined disease entity, myelodysplastic neoplasm (MDS)/AML is unknown. To assess the relationship between disease type, pre-HCT MRD, and post-HCT outcomes, we retrospectively analyzed 1265 adults with MDS/AML (n = 151) or AML (n = 1114) who received a first allograft in first or second morphologic remission at a single institution between April 2006 and March 2023.

Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study.

Background: We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use.

Method: In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3.

Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors.

Purpose: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316).

Cryopreservation of Growth Factor-Mobilized Peripheral Blood Stem Cells Does Not Compromise Major Outcomes after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience.

During the Coronavirus disease 2019 pandemic, cryopreservation of allogeneic donor stem cell products ensured the availability of products at the start of conditioning for hematopoietic cell transplantation (HCT). Following recommendations from unrelated donor registries, including the National Marrow Donor Program, many centers began to cryopreserve related donor peripheral blood stem cell (PBSC) products. Throughout this process, several centers have published outcomes with cryopreserved versus fresh products, some with conflicting results.

EASIX-1year and late mortality after allogeneic stem cell transplantation.

Patients with hematological malignancies who survive the first year after allogeneic stem cell transplantation (allo-SCT) without relapse have a substantial risk of nonrelapse mortality (NRM) and missing predictive markers. The Endothelial Activation and Stress Index (EASIX) predicts endothelial complications and NRM early after allo-SCT. We hypothesized that EASIX assessed 1 year after allo-SCT in survivors who were disease free may predict late NRM.

Acute graft-versus-host disease.

Acute graft-versus-host disease (GVHD) is a common immune complication that can occur after allogeneic haematopoietic cell transplantation (alloHCT). Acute GVHD is a major health problem in these patients, and is associated with high morbidity and mortality. Acute GVHD is caused by the recognition and the destruction of the recipient tissues and organs by the donor immune effector cells.

Analysis of Antibiotic Exposure and Development of Acute Graft-vs-Host Disease Following Allogeneic Hematopoietic Cell Transplantation.

Importance: Certain antibiotic exposures have been associated with increased rates of acute graft-vs-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Since antibiotic exposure can both affect and be affected by infections, analyzing time-dependent exposure in the presence of multiple potential confounders, including prior antibiotic exposures, poses specific analytical challenges, necessitating both a large sample size and unique approaches.

Objective: To identify antibiotics and antibiotic exposure timeframes associated with subsequent aGVHD.

Cytomegalovirus breakthrough and resistance during letermovir prophylaxis.

Letermovir is a relatively new antiviral for prophylaxis against cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT). CMV-seropositive HCT recipients who received letermovir prophylaxis from 2018 to 2020 at our center were evaluated for letermovir resistance and breakthrough CMV reactivation. Two-hundred twenty-six letermovir recipients were identified and 7/15 (47%) with CMV DNAemia ≥200 IU/mL were successfully genotyped for UL56 resistance.

Association between Prior Cytotoxic Therapy, Antecedent Hematologic Disorder, and Outcome after Allogeneic Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia.

(1) Background: Secondary acute myeloid leukemia (AML), i.e., AML arising from prior therapy (therapy-related) and/or an antecedent hematologic disorder (AHD) is generally associated with worse outcomes compared to de novo AML.

Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation.

The kinetics of early and late cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin inhibitor plus posttransplantation cyclophosphamide (PTCy; n = 44), mycophenolate mofetil (MMF; n = 414), or methotrexate (MTX; n = 322). Transplantation occurred between 2007 and 2018; CMV monitoring/management followed uniform standard practice.

Comparison of reduced intensity and nonmyeloablative conditioning for adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation in first or second remission.

Reduced intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning regimens have expanded use of allogeneic hematopoietic cell transplantation (HCT) in AML to include older and medically less-fit patients, but relative efficacies and toxicities remain poorly defined. Here, we analyzed outcomes from 343 adults transplanted in remission after RIC (n = 137) or NMA (n = 206) conditioning between 2006 and 2021. The characteristics of RIC and NMA HCT patients were similar except that RIC patients were younger and their time between most recent remission achievement and allografting was shorter.

Small-scale (sub-organ and cellular level) alpha-particle dosimetry methods using an iQID digital autoradiography imaging system.

Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery and efficient tumor cell killing. However, these properties create sub-organ dose deposition effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine the spatial distribution of absorbed dose from alpha-emitting radionuclides in tissues using digital autoradiography activity images from an ionizing-radiation quantum imaging detector (iQID).

The ASTCT-NMDP ACCESS Initiative: A Collaboration to Address and Sustain Equal Outcomes for All across the Hematopoietic Cell Transplantation and Cellular Therapy Ecosystem.

The American Society for Transplantation and Cellular Therapy (ASTCT) and the National Marrow Donor Program (NMDP) have formed the ACCESS Initiative to address and reduce barriers to hematopoietic cell transplantation (HCT) and cellular therapy (CT) in an effort to ensure equal access and outcomes for all patients in need. In addition to cellular therapy physicians, the initiative includes program administrators, health policy and health equity experts, health service researchers, participants from commercial payer organizations, and federal stakeholders. The inaugural ASTCT-NMDP ACCESS Workshop was held in Washington, DC on July 28 and 29, 2022, wherein committee members met to discuss and to define goals for 3 focus areas: awareness, poverty, and racial and ethnic inequity.