Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined.

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively.

Novel machine learning technique further clarifies unrelated donor selection to optimize transplantation outcomes.

We investigated the impact of donor characteristics on outcomes in allogeneic hematopoietic cell transplantation (HCT) recipients using a novel machine learning approach, the Nonparametric Failure Time Bayesian Additive Regression Trees (NFT BART). NFT BART models were trained on data from 10 016 patients who underwent a first HLA-A, B, C, and DRB1 matched unrelated donor (MUD) HCT between 2016 and 2019, reported to the Center for International Blood and Marrow Transplant Research, then validated on an independent cohort of 1802 patients. The NFT BART models were adjusted based on recipient, disease, and transplant variables.

Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors.

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.

The Evolution of Hematopoietic Stem Cell Transplantation to Overcome Access Disparities: The Role of NMDP.

NMDP recognizes that despite advances in hematopoietic stem cell transplantation (HSCT) and other cell therapies, not all patients have equitable access to treatment, and disparities in outcomes remain. This paper explores the recent work of NMDP to accelerate progress and expand access to more patients through transformative clinical research, particularly in the use of mismatched unrelated donors for HSCT.

Optimal Donor Selection Across Multiple Outcomes For Hematopoietic Stem Cell Transplantation By Bayesian Nonparametric Machine Learning.

Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative treatment options for patients suffering from life-threatening hematologic malignancies; yet, the possible adverse complications can be serious even fatal. Matching between donor and recipient for 4 of the HLA genes is widely accepted and supported by the literature. However, among 8/8 allele matched unrelated donors, there is less agreement among centers and transplant physicians about how to prioritize donor characteristics like additional HLA loci (DPB1 and DQB1), donor sex/parity, CMV status, and age to optimize transplant outcomes.

Long-term outcomes of peripheral blood stem cell unrelated donors mobilized with filgrastim.

Allogeneic hematopoietic cell transplantation is a life-saving procedure used to treat a variety of devastating diseases. It requires hematopoietic stem cells collected via filgrastim-mobilized peripheral blood stem cells (PBSCs) or bone marrow (BM) harvest from volunteer unrelated donors (URDs). There is a paucity of safety data regarding donors' long-term adverse events.

Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance.

Data on recent bone marrow harvest (BMH) collections from the NMDP has shown that bone marrow (BM) quality has decreased based on total nucleated cell count in the product. To ensure that quality BM products are available to all recipients, the NMDP Marrow Alliance was formed in April 2021 to increase the capability of BM collection centers to safely deliver high-quality products consistently and to identify and disseminate guidelines for performing BMH. This white paper describes the best practices for BMH as defined by the NMDP Marrow Alliance.

Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of .

Purpose: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of () AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.

Expanding donor options: haploidentical transplant recipients are also highly likely to have a 7/8-matched unrelated donor.

The use of haploidentical related donor (HRD) hematopoietic cell transplants (HCTs) in the United States grew by more than fourfold in the last decade, driven mainly by use of posttransplant cyclophosphamide (PTCy)-based graft-versus-host-disease prophylaxis. However, not all patients have a suitable HRD available. In this study, we explored the existence of unrelated donors (URDs) on the National Marrow Donor Program (NMDP) registry at the 8/8- or 7/8-match level for patients receiving HRD HCT in the United States and reporting to the Center for International Blood and Marrow Transplant Research between 2013 and 2020.

Existence of HLA-Mismatched Unrelated Donors Closes the Gap in Donor Availability Regardless of Recipient Ancestry.

In patients without a matched sibling donor (MSD) or well-matched unrelated donor (MUD), hematopoietic cell transplantation (HCT) can still be successful when using an HLA-mismatched unrelated donor (MMUD) in combination with post-transplantation cyclophosphamide (PTCy), abatacept, or other novel approaches. This may allow clinicians to choose a suitable donor from a wide range of donor options while optimizing other donor selection characteristics, including donor age. We hypothesized that allowing for a 5/8 HLA match level considering high-resolution matching at HLA-A, -B, -C and -DRB1, there is a potential to close the donor availability gap for all patients regardless of their race/ethnicity.

Measurable Residual before Allogeneic Transplant for Acute Myeloid Leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated or -ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as , at this treatment landmark however remains incompletely defined.

Reducing barriers of access and care related to hematopoietic cell transplantation and cellular therapy: The mission-driven role of the national marrow donor program.

The treatment of malignant and nonmalignant hematologic disorders continues to benefit from significant scientific advancement and progress in the use of hematopoietic cell transplantation and cellular therapies. However, barriers associated with receiving these lifesaving treatments and care remain, which necessitate innovative approaches to overcome, so all persons in need can receive these therapies. This article reviews barriers to receiving hematopoietic cell transplantation and cellular therapies, and highlights novel approaches taken by the National Marrow Donor Program in reducing barriers for all patients in need.

Clinical impact of cryopreservation of allogeneic hematopoietic cell grafts during the onset of the COVID-19 pandemic.

At the onset of the COVID-19 pandemic, the National Marrow Donor Program mandated the cryopreservation of hematopoietic cell grafts from volunteer unrelated donors because of numerous patient and donor safety concerns and logistical hurdles. Using the Center for International Blood and Marrow Transplant Research outcomes database, we report the impact of cryopreservation on overall survival (OS) and other outcomes within 1 year after hematopoietic cell transplantation (HCT). We analyzed 1543 recipients of cryopreserved allografts receiving HCT at US centers during the first 6 months of the pandemic and compared them with 2499 recipients of fresh allografts during a 6-month period in 2019.

Real-World Data Showing Trends and Outcomes by Race and Ethnicity in Allogeneic Hematopoietic Cell Transplantation: A Report from the Center for International Blood and Marrow Transplant Research.

The use of HLA-mismatched donors could enable more patients with ethnically diverse backgrounds to receive allogeneic hematopoietic cell transplantation (HCT) in the United States. However, real-world trends and outcomes following mismatched donor HCT for diverse patients remain largely undefined. We conducted this study to determine whether the use of mismatched donor platforms have increased the access to allogeneic HCT for ethnically diverse patients, particularly through the application of novel graft-versus-host disease (GVHD) prophylaxis regimens, and whether outcomes for diverse patients are comparable to those of non-Hispanic White patients.

DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant.

Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized.

Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants.

Wearable sensor-based performance status assessment in cancer: A pilot multicenter study from the Alliance for Clinical Trials in Oncology (A19_Pilot2).

Clinical performance status is designed to be a measure of overall health, reflecting a patient's physiological reserve and ability to tolerate various forms of therapy. Currently, it is measured by a combination of subjective clinician assessment and patient-reported exercise tolerance in the context of daily living activities. In this study, we assess the feasibility of combining objective data sources and patient-generated health data (PGHD) to improve the accuracy of performance status assessment during routine cancer care.