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A compass for those with relapsed leukemia after transplant

Award Number: R01CA289886
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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A compass for those with relapsed leukemia after transplant - ABSTRACT Relapse of leukemia occurs in nearly half of patients after hematopoietic cell transplantation (HCT). While there are a growing number of therapeutic options for leukemic relapse after HCT, we lack a clinical assay capable of simultaneously detecting disease and triaging patients to treatment which will most likely benefit them. In this application, we propose to rigorously evaluate and employ novel single-cell genomic methods and their accompanying computational approaches to detect disease at low levels, inform mechanisms of relapse, and direct future therapy. In Aim 1, we will optimize computational methods for detecting natural genetic variation between donor and recipient, a diagnostic maneuver we believe will improve the sensitivity of detecting malignant cells after HCT. We will then validate these methods using samples from patients in a retrospective fashion. To provide insight into mechanisms of relapse, we have developed a novel molecular approach for identifying perturbations in HLA and related genes, a common means by which leukemia evades the immune system after HCT. In Aim 2, we will validate this method in a manner that explores the lower limit of detection for HLA- perturbed cells. Finally, in Aim 3, we will build on decades of work using flow cytometry to assess the heterogeneity of myeloid neoplasms by integrating our single-cell molecular measures with cell-surface immunophenotype. Using this approach, we seek to define common molecular signatures in leukemia-initiating cells (LICs), a subset of cells in myeloid neoplasms thought to be a chemo-resistant reservoir of leukemia. The proposed studies will establish a new method for surveillance of residual disease after HCT, which we believe will provide a deeper level of confidence and insight into leukemic relapse post-transplant. We expect these studies to form the foundational preclinical data for a single-cell genomics clinical assay capable of risk-stratifying patients with early evidence of leukemic relapse after HCT.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $2,061,389 )
2026	2026	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	001	3	6/19/2026	EXTENSION WITH OR WITHOUT FUNDS	$2,061,389
2026	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	000	2	6/9/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,061,389

Issue Date FY: 2025 ( Subtotal = $701,179 )
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	000	2	6/23/2025	NON-COMPETING CONTINUATION	$701,179
														Subtotal = $701,179

Issue Date FY: 2024 ( Subtotal = $734,482 )
2024	2024	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Detection and Diagnosis Research	000	1	5/22/2024	NEW	$734,482
														Subtotal = $734,482

Grand Total All Awards = $3,497,050

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A compass for those with relapsed leukemia after transplant

Award Number: R01CA289886

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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