Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia

Laura W Dillon; Gege Gui; Niveditha Ravindra; Georgia Andrew; Devdeep Mukherjee; Zoë C Wong; Ying Huang; Jason Gerhold; Matt Holman; Julian D’Angelo; Jeffrey Miller; Jake Higgins; Jesse J Salk; Jeffery J Auletta; Firas El Chaer; Steven M Devine; Antonio Martin Jimenez-Jimenez; Marcos J G De Lima; Mark R Litzow; Partow Kebriaei; Wael Saber; Stephen R Spellman; Scott L Zeger; Kristin M Page; Christopher S Hourigan

doi:10.1001/jamaoncol.2024.0985

. 2024 May 2;10(8):1104–1110. doi: 10.1001/jamaoncol.2024.0985

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia

Laura W Dillon ¹, Gege Gui ¹, Niveditha Ravindra ¹, Georgia Andrew ¹, Devdeep Mukherjee ¹, Zoë C Wong ¹, Ying Huang ², Jason Gerhold ², Matt Holman ², Julian D’Angelo ², Jeffrey Miller ², Jake Higgins ³, Jesse J Salk ^3,⁴, Jeffery J Auletta ^5,⁶, Firas El Chaer ⁷, Steven M Devine ⁵, Antonio Martin Jimenez-Jimenez ⁸, Marcos J G De Lima ⁶, Mark R Litzow ⁹, Partow Kebriaei ¹⁰, Wael Saber ^11,¹², Stephen R Spellman ^5,¹², Scott L Zeger ¹³, Kristin M Page ^5,¹¹, Christopher S Hourigan ^1,^14,^✉

¹Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

²Invivoscribe, San Diego, California

³TwinStrand Biosciences, Seattle, Washington

⁴University of Washington School of Medicine, Seattle

⁵Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota

⁶The Ohio State University College of Medicine, Columbus

⁷University of Virginia, Charlottesville

⁸Sylvester Comprehensive Cancer Center, Miami, Florida

⁹Mayo Clinic, Rochester, Minnesota

¹⁰The University of Texas MD Anderson Cancer Center, Houston

¹¹Medical College of Wisconsin, Milwaukee

¹²National Marrow Donor Program, Minneapolis, Minnesota

¹³Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

¹⁴Virginia Tech Fralin Biomedical Research Institute Cancer Research Center, Washington, DC

Accepted for Publication: December 7, 2023.

Published Online: May 2, 2024. doi:10.1001/jamaoncol.2024.0985

^✉

Corresponding Author: Christopher S. Hourigan, DM, DPhil, Virginia Tech Fralin Biomedical Research Institute Cancer Research Center, 7144 13th Place NW, Washington, DC 20012 (hourigan@vt.edu).

Author Contributions: Dr Dillon and Ms Gui had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Dillon and Ms Gui contributed equally to this work.

Concept and design: Dillon, Gui, Gerhold, Holman, Miller, Hourigan.

Acquisition, analysis, or interpretation of data: Dillon, Ravindra, Andrew, Mukherjee, Wong, Huang, Holman, D’Angelo, Higgins, Salk, Auletta, El Chaer, Devine, Jimenez-Jimenez, De Lima, Litzow, Kebriaei, Saber, Spellman, Zeger, Page, Hourigan.

Drafting of the manuscript: Dillon, Gui, Auletta, Saber, Page, Hourigan.

Critical review of the manuscript for important intellectual content: Dillon, Ravindra, Andrew, Mukherjee, Wong, Huang, Gerhold, Holman, D’Angelo, Miller, Higgins, Salk, Auletta, El Chaer, Devine, Jimenez-Jimenez, De Lima, Litzow, Kebriaei, Spellman, Zeger, Hourigan.

Statistical analysis: Dillon, Gui, Holman, D’Angelo, Saber, Zeger, Page.

Obtained funding: Salk, Hourigan.

Administrative, technical, or material support: Dillon, Andrew, Wong, Huang, Gerhold, Holman, D’Angelo, Miller, Higgins, Spellman.

Supervision: Huang, Gerhold, Auletta, El Chaer, Devine, Saber, Hourigan.

Conflict of Interest Disclosures: Dr Huang reported personal fees from Invivoscribe during the conduct of the study as well as personal fees from Invivoscribe outside the submitted work. Dr Gerhold reported nonfinancial support from Invivoscribe outside the submitted work. Dr Salk reported grants from the National Cancer Institute during the conduct of the study and has a patent for duplex sequencing licensed to TwinStrand Biosciences. Dr Auletta serves on the advisory board for AscellaHealth outside the submitted work. Dr El Chaer reported grants from BMS, Celgene, SPD Oncology, Sanofi, Fibrogen, MEI Pharma, Novartis, Arog Pharmaceutical, and Amgen as well as personal fees from SPD Oncology, Amgen, AbbVie, and MorphoSys during the conduct of the study. Dr Spellman reported grants from the Office of Naval Research during the conduct of the study. Dr Hourigan reported research funding from the Foundation of the National Institutes of Health Acute Myeloid Leukemia Measurable Residual Disease Biomarkers Consortium during conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. The National Heart, Lung, and Blood Institute receives research funding for the laboratory of Dr Hourigan from the Foundation of the National Institutes of Health Acute Myeloid Leukemia Measurable Residual Disease Biomarkers Consortium. Support for the Foundation of the National Institutes of Health Acute Myeloid Leukemia Measurable Residual Disease Biomarkers Consortium was provided by AbbVie, Amgen, AstraZeneca, Genentech, Gilead Sciences, GSK, Jazz Pharmaceuticals, LGC Clinical Diagnostics, Novartis, Syndax Pharmaceuticals, and Sysmex Inostics. In-kind donations of standards and methods materials and equipment to support the project were provided to the Foundation of the National Institutes of Health Acute Myeloid Leukemia Measurable Residual Disease Biomarkers Consortium by AccuGenomics, Bio-Rad Laboratories, Invivoscribe, LGC Clinical Diagnostics, Mission Bio, 10x Genomics, Thermo Fisher Scientific, TwinStrand Biosciences, and Twist Bioscience Corporation. The Center for International Blood and Bone Marrow Transplant Research is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases; grants U24HL138660 and U24HL157560 from National Heart, Lung, and Blood Institute and National Cancer Institute; grant U24CA233032 from the National Cancer Institute; grants OT3HL147741 and U01HL128568 from the National Heart, Lung, and Blood Institute; grants HHSH250201700005C, HHSH250201700006C, and HHSH250201700007C from the Health Resources and Services Administration; and grants N00014-20-1-2832 and N00014-21-1-2954 from the Office of Naval Research.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US government.

Data Sharing Statement: See Supplement 2.

Additional Information: Sequencing was performed in the National Heart, Lung, and Blood Institute Intramural DNA Sequencing and Genomics Core. This work used the computational resources of the National Institutes of Health High Performance Computing Biowulf cluster.

^✉

Corresponding author.

PMCID: PMC11066770 PMID: 38696205

Key Points

Question

Are different levels of acute myeloid leukemia (AML) measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplant (HCT) associated with different posttransplant clinical outcomes?

Findings

In this cohort study including 537 patients, adults with AML in first remission prior to allogeneic HCT with persistence of FLT3 internal tandem duplication (ITD) at a variant allele fraction of 0.01% or higher had increased relapse and death compared with those with lower levels detected. Patients with no detectable FLT3-ITD had the best outcomes.

Meaning

In this study, for adults with FLT3-ITD AML, there was a dose-dependent correlation between pretransplant level of persistent FLT3-ITD MRD and clinical outcomes.

This cohort study examines the association between pre–allogeneic hematopoietic cell transplant FLT3 internal tandem duplication measurable residual disease level with relapse and death posttransplant in adults with acute myeloid leukemia in first complete remission.

Abstract

Importance

Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown.

Objective

To examine the association between pre–allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR.

Design, Setting, and Participants

In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023.

Exposure

Centralized DNA sequencing for FLT3-ITD in pre–allogeneic HCT first CR blood using a commercially available kit.

Main Outcomes and Measures

The primary outcomes were overall survival and cumulative incidence of relapse, with non–relapse-associated mortality as a competing risk post–allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points.

Results

Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning.

Conclusions and Relevance

This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

Introduction

Acute myeloid leukemia (AML) is a rare, deadly group of blood cancers.¹ Even those who achieve complete remission (CR) and then receive a consolidative allogeneic hematopoietic cell transplant (HCT) remain at risk of relapse and death.^2,3 FLT3 internal tandem duplication (ITD) is one of the most common genetic lesions associated with AML.⁴ We and others have recently reported a dramatically increased risk of relapse and death when persistent FLT3-ITD variants are still detectable in adults in first CR from AML before allogeneic HCT.^5,6,7,8,9 Translating the evidence of measurable residual disease (MRD) into clinical practice, however, requires the widespread availability of testing and a comprehensive understanding of the clinical implications of FLT3-ITD detection at specific thresholds.^10,11 To evaluate the association of residual disease burden levels and validate generalizability using an orthogonal approach, we performed analysis on our Pre-MEASURE cohort using a commercially available FLT3-ITD MRD kit.

Methods

This cohort study included patients 18 years and older from the Pre-MEASURE study⁶ who received allogeneic HCT for FLT3-ITD AML during first CR at Center for International Blood and Bone Marrow Transplant Research (CIBMTR) reporting sites in the US between March 2013 and February 2019. Patient self-reported race and ethnicity data were collected by CIBMTR. Patients provided written informed consent for participation in the National Marrow Donor Program Institutional Review Board–approved CIBMTR database and repository protocols. Research was performed in compliance with all applicable federal regulations pertaining to the protection of human research participants and with approval of the CIBMTR observational research group. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

The FLT3-ITD MRD assay next-generation sequencing (NGS) kit (IVS; Invivoscribe), validated to detect an FLT3-ITD variant down to a variant allele fraction (VAF) of at least 0.005%, was used following clinical testing standards (eFigure 1 in Supplement 1). Results were compared with those previously reported using an anchored multiplex polymerase chain reaction–based (AMP) targeted NGS assay. In a subset of patients who relapsed within the first year but had no FLT3-ITD variant detected in pretransplant remission, the presence of AML-associated variants down to 0.01% VAF was examined using a custom duplex DNA sequencing panel (TwinStrand Biosciences, Inc) (eTable 4 in Supplement 1). Overall survival (OS) and cumulative incidence of relapse with non–relapse-associated mortality as a competing risk were estimated by Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models. P values less than .05 were considered statistically significant, and all P values were 2-tailed. Analyses were conducted using R version 4.3.2 (The R Foundation). Additional details are provided in the eMethods in Supplement 1.

Results

A total of 537 of 608 patients reported as having FLT3-ITD AML in the Pre-MEASURE study⁶ had sufficient sample remaining for repeated analysis (eFigure 2 in Supplement 1). Of these, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Those examined and excluded had similar clinical characteristics (eTable 1 in Supplement 1). The median (IQR) follow-up time was 35.9 (24.4-59.5) months for censored patients. In total, 173 patients (32.2%) relapsed (median [range] time to relapse, 5.2 [0.7-52.1] months) and 219 (40.8%) died (median [range] time to death, 10.1 [0-88.4] months) after allogeneic HCT (eFigure 3 in Supplement 1).

Persistent FLT3-ITD variants in pre–allogeneic HCT blood evaluated by IVS (eTable 2 in Supplement 1) were compared with those previously reported by AMP⁶ with the same VAF cutoff (0.01%) to define MRD positivity. The MRD calls and length of the detected FLT3-ITD variants were highly correlated between the 2 assays (Figure 1A). At 3 years, patients with positive findings had increased relapse rate (68% vs 26%; difference, 42 percentage points; 95% CI, 31-54; P < .001) and decreased OS (24% vs 65%; difference, −41 percentage points; 95% CI, −52 to −30; P < .001) by IVS, which was comparable with AMP results (Figure 1B).

Figure 1. — A, Comparison of variant allele fraction (VAF) and length of residual *FLT3*-ITD variants detected in pretransplant blood at a VAF of 0.01% or greater as detected by next-generation sequencing using the Invivoscribe (IVS) *FLT3*-ITD measurable residual disease (MRD) assay or an anchored multiple polymerase chain reaction–based (AMP) assay. The Pearson correlation is shown in the graph, and the value of equivalence line is displayed as a dashed line. B, Cumulative incidence of relapse and overall survival are shown for patients with *FLT3*-ITD variants based on the presence (MRD positive) or absence (MRD negative) of residual *FLT3*-ITD variants, with the positive group defined by a VAF of 0.01% or greater in the pre–allogeneic hematopoietic cell transplant blood. Bp indicates base pairs.

The IVS test had a superior limit of detection compared with the AMP test, allowing the investigation of alternative VAF thresholds. IVS identified 263 FLT3-ITD variants with a median (range) VAF of 0.005% (0.0002%-44%) and median (range) length of 51 (5-228) base pairs (eFigure 4 in Supplement 1). Patients with positive findings on IVS had a median (range) of 1 (1-15) variant and a median (range) maximum VAF of 0.01% (0.0003%-44%). Without assigning any VAF MRD threshold (VAF greater than 0%), 177 patients (33.0%) had detectable FLT3-ITD, which was associated with increased relapse rate and decreased OS compared with those testing negative (eFigure 5 in Supplement 1).

Stratifying patients by their level of residual FLT3-ITD revealed an increased risk of relapse and death for those with higher disease burden (Figure 2A; eFigure 6 in Supplement 1). In multivariable analyses, residual FLT3-ITD was the variable most associated with relapse and OS, with a dose-dependent correlation with disease burden (Figure 2B). Any detectable level of residual FLT3-ITD exhibited increased risk, with VAFs of 0.01% or greater having the highest risk.

Figure 2. — A, Cumulative incidence of relapse and overall survival are shown for patients with *FLT3*-ITD variants based on the presence (measurable residual disease [MRD] positive) or absence (MRD negative) of residual *FLT3*-ITD variants as detected by next-generation sequencing using the Invivoscribe (IVS) *FLT3*-ITD MRD assay, with positive patients grouped by residual disease burden level. B, Multivariable competing-risks regression for relapse and Cox regression analysis for overall survival for residual *FLT3*-ITD variants as detected by the IVS assay grouped by residual disease burden level. Models were selected stepwise using MRD status and baseline clinical characteristics. NMA indicates nonmyeloablative conditioning; RIC, reduced-intensity conditioning without melphalan; VAF, variant allele fraction.

Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning regimens had an increased risk of relapse and death compared with those receiving myeloablative conditioning or reduced-intensity conditioning with melphalan (Figure 2B). Patients receiving myeloablative conditioning or reduced-intensity conditioning with melphalan had decreased rates of relapse and death compared with those receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning for both high (VAF of 0.01% or greater) and low (VAF greater than 0 but less than 0.01%) residual FLT3-ITD levels (Figure 3A). Interestingly, patients with low residual FLT3-ITD level (VAF greater than 0 but less than 0.01%) receiving myeloablative conditioning or reduced-intensity conditioning with melphalan had similar relapse risk to patients without detectable residual FLT3-ITD levels receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning.

Figure 3. — A, Cumulative incidence of relapse and overall survival for patients with *FLT3*-ITD variants based on the presence (measurable residual disease [MRD] positive) or absence (MRD negative) of residual *FLT3*-ITD variants, variant allele fraction (VAF) ranges, and conditioning regimen received. B, Heatmap illustrating patients who were *FLT3*-ITD MRD negative pretransplant and experienced relapse within the first year after allogeneic hematopoietic cell transplant and their relapse month, age group, conditioning regimen, and residual variant status for variants in genes other than *FLT3*-ITD. Patients were ordered by their time to relapse from the shortest to the longest. Residual variant status is denoted as high or unclear based on relevance of the residually mutated gene. Variants in signaling pathways or escape genes are more likely associated with the leukemia clone,¹¹ while variants in genes such as *TP53* and *CBL* are frequently observed after chemotherapy^12,13,14 and could be associated with clonal hematopoiesis¹⁵ unrelated to the leukemic clone. MAC indicates myeloablative conditioning; Mel, reduced-intensity conditioning with melphalan; NMA, nonmyeloablative conditioning; RIC, reduced-intensity conditioning without melphalan.

Finally, while pretransplant FLT3-ITD MRD status is highly associated with relapse, such testing is not infallible. One potential explanation for false-negative results is the category of CR status² at the time of MRD testing. Complete blood count information at first CR was available for 294 patients (54.7%). At 3 years, patients in full CR (240 [81.6%]) with residual FLT3-ITD variants had significantly higher rates of relapse (57% vs 26%; difference, 31 percentage points; 95% CI, 17-44; P < .001) and decreased OS (32% vs 67%; difference, −35 percentage points; 95% CI, −48 to −21; P < .001) compared with those testing negative, while patients in CR with suboptimal hematologic recovery (54 [18.4%]) showed similar trends without statistical significance (eFigure 7 in Supplement 1).

Another possible explanation for false-negative FLT3-ITD MRD test results would be the presence of a residual AML clone without FLT3-ITD. Exploratory deep DNA sequencing of 15 other genes frequently mutated in AML was performed on pretransplant samples of 52 patients who experienced relapse in the year after transplant despite testing negative for FLT3-ITD MRD before transplant. Of these, 44 had another variant detected pretransplant, including 4 patients with previously reported NPM1 variants⁶ (Figure 3B; eTable 3 in Supplement 1).

Discussion

This study demonstrates a dose-dependent correlation between persistent FLT3-ITD burden in the blood of adults with FLT3-ITD AML in first CR prior to allogeneic HCT and posttransplant clinical outcomes. Patients with the highest risk of relapse and death after transplant (approximately 1 in 6) can be identified by a VAF MRD threshold of 0.01% or greater in pretransplant remission blood using a simply implemented, commercially available testing kit for persistent FLT3-ITD. Patients with residual FLT3-ITD levels detected at lower VAFs had better outcomes but still worse than those testing negative. Including VAF less than 0.01% in an MRD definition would include more relapsing patients at the expense of specifically identifying those patients at highest risk. The FLT3-ITD VAF MRD threshold selected may differ based on the use case of the test, the nature of the proposed intervention (if any), and the planned retesting strategy. At every VAF level, higher-intensity conditioning regimens were associated with a reduced risk of relapse and death. The observation that relapsing patients who did not have persistent FLT3-ITD detected in remission often had variants in other AML-associated genes detectable in the same pretransplant sample is descriptive but intriguing, highlighting the opportunity for continued refinement of AML MRD testing approaches.

Conclusions

This study of the Pre-MEASURE cohort provides strong justification for NGS-based AML MRD clinical testing for persistent FLT3-ITD prior to allogeneic HCT. An MRD definition of VAF of 0.01% or greater identified patients with very high risk of relapse and poor OS when treated according to the current standard of care.

Supplement 1.

eMethods.

eFigure 1. Validation of the Invivoscribe FLT3-ITD MRD Assay

eFigure 2. Patient Selection Flowchart

eFigure 3. Baseline Characteristics for FLT3-ITD Mutated AML Patients and the Association With Clinical Outcomes After Allogeneic Hematopoietic Cell Transplant

eFigure 4. FLT3-ITD Residual Disease Burden Levels as Detected by Multiple Next-Generation Sequencing Assays

eFigure 5. FLT3-ITD MRD Status for FLT3-ITD Mutated AML Patients and the Association With Clinical Outcomes After Allogeneic Hematopoietic Cell Transplant

eFigure 6. FLT3-ITD MRD Status by Different Variant Allele Fraction (VAF) Groups for FLT3-ITD Mutated AML Patients and the Association With Clinical Outcomes After Allogeneic Hematopoietic Cell Transplant

eFigure 7. NGS MRD Status for FLT3-ITD Mutated AML Patients and the Association With Clinical Outcomes After Allogeneic Hematopoietic Cell Transplant Stratified by Complete Remission (CR) Status

eTable 1. Patient Baseline Clinical Characteristics

eTable 2. Residual FLT3-ITD Variants Detected in the Blood of AML Patients Prior to Transplant Using the Invivoscribe FLT3-ITD MRD Assay

eTable 3. Residual Variants Other Than FLT3-ITD Detected in the Blood of FLT3-ITD MRD False-Negative AML Patients Prior to Transplant

eTable 4. Duplex Sequencing Panel Target Regions

eReferences.

jamaoncol-e240985-s001.pdf^{(1.7MB, pdf)}

Supplement 2.

Data Sharing Statement

jamaoncol-e240985-s002.pdf^{(16.4KB, pdf)}

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement 1.

eMethods.

eFigure 1. Validation of the Invivoscribe FLT3-ITD MRD Assay

eFigure 2. Patient Selection Flowchart

eFigure 3. Baseline Characteristics for FLT3-ITD Mutated AML Patients and the Association With Clinical Outcomes After Allogeneic Hematopoietic Cell Transplant

eFigure 4. FLT3-ITD Residual Disease Burden Levels as Detected by Multiple Next-Generation Sequencing Assays

eFigure 5. FLT3-ITD MRD Status for FLT3-ITD Mutated AML Patients and the Association With Clinical Outcomes After Allogeneic Hematopoietic Cell Transplant

eTable 1. Patient Baseline Clinical Characteristics

eTable 2. Residual FLT3-ITD Variants Detected in the Blood of AML Patients Prior to Transplant Using the Invivoscribe FLT3-ITD MRD Assay

eTable 3. Residual Variants Other Than FLT3-ITD Detected in the Blood of FLT3-ITD MRD False-Negative AML Patients Prior to Transplant

eTable 4. Duplex Sequencing Panel Target Regions

eReferences.

jamaoncol-e240985-s001.pdf^{(1.7MB, pdf)}

Supplement 2.

Data Sharing Statement

jamaoncol-e240985-s002.pdf^{(16.4KB, pdf)}

[cbr240008r1] 1.Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136-1152. doi: 10.1056/NEJMra1406184 [DOI] [PubMed] [Google Scholar]

[cbr240008r2] 2.Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi: 10.1182/blood.2022016867 [DOI] [PubMed] [Google Scholar]

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PERMALINK

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia

Laura W Dillon, PhD

Gege Gui, ScM

Niveditha Ravindra, MD

Georgia Andrew, BSc

Devdeep Mukherjee, PhD

Zoë C Wong, BS

Ying Huang, PhD

Jason Gerhold, BS

Matt Holman, BSc

Julian D’Angelo, BSc

Jeffrey Miller, PhD

Jake Higgins, PhD

Jesse J Salk, MD, PhD

Jeffery J Auletta, MD

Firas El Chaer, MD

Steven M Devine, MD

Antonio Martin Jimenez-Jimenez, MD

Marcos J G De Lima, MD

Mark R Litzow, MD

Partow Kebriaei, MD

Wael Saber, MD

Stephen R Spellman, MBS

Scott L Zeger, PhD

Kristin M Page, MD

Christopher S Hourigan, DM, DPhil

Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Exposure

Main Outcomes and Measures

Results

Conclusions and Relevance

Introduction

Methods

Results

Figure 1. Residual FLT3 Internal Tandem Duplication (ITD) Variants in Patients With Acute Myeloid Leukemia (AML) Prior to Allogeneic Hematopoietic Cell Transplant.

Figure 2. Association of FLT3 Internal Tandem Duplication (ITD) Residual Disease Burden Level and Clinical Outcomes.

Figure 3. Evaluation of Potential Factors Modifying the Association of Residual FLT3 Internal Tandem Duplication (ITD) and Clinical Outcomes.

Discussion

Conclusions

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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