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Plerixafor for allogeneic hematopoietic stem cell transplantation

Award Number: K08HL103780
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2014
PERIOD OF PERFORMANCE END DATE: 06/30/2016

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Plerixafor for allogeneic hematopoietic stem cell transplantation - DESCRIPTION (provided by applicant): Hematopoietic cell transplantation (HCT) provides a potentially curative treatment for a wide variety of diseases. HCT, however, is complicated by high incidence of transplant-related mortality, graft failure and graft versus host disease (GvHD). The interaction of stromal derived factor-1 (SDF-1) with CXCR4 chemokine receptor plays an indispensable role in hematopoietic stem cell homing and engraftment. We hypothesize that blocking the SDF-1/CXCR4 interaction with a specific CXCR4 antagonist would selectively enhance donor cell reconstitution in allogeneic HCT. Plerixafor is a highly specific and reversible antagonist of CXCR4 and will be used in the current study. Our recent studies in a congeneic mouse transplant model demonstrated that post-transplant administration of plerixafor significantly improved animal survival and selectively enhanced donor cell engraftment. This selective enhancement of donor cell reconstitution results from combined effects of mobilization of residual recipient stem cells by plerixafor and selective survival advantage of donor stem cells. The objectives of this proposal are to perform pivotal translational studies to move our study into a phase I/II clinical trial at the end of this award and to further dissect the mechanisms of plerixafor and the regulation of CXCR4 signaling. We have 2 specific aims. Our Aim 1 is to investigate the efficacy of plerixafor in enhancing donor cell engraftment in several allogeneic mouse transplant models that are directly relevant to clinical applications. Our Aim 2 is to further dissect the mechanisms through which plerixafor enhances donor cell reconstitution and to understand the regulation of CXCR4 signaling. Successful accomplishment of these aims will have important implications in HCT and will benefit patients with HCT. Furthermore, our study will shed new lights into the role of CXCR4 in hematopoietic stem cell homing, mobilization and expansion, as well as the regulation of CXCR4 signaling.


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: 2017 ( Subtotal = -$318 )
2017	2015	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Blood Diseases and Resources Research	000	6	11/23/2016	NON-COMPETING CONTINUATION	-$318
														Subtotal = -$318

Issue Date FY: 2015 ( Subtotal = $126,549 )
2015	2015	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Blood Diseases and Resources Research	000	6	6/12/2015	NON-COMPETING CONTINUATION	$126,549
														Subtotal = $126,549

Issue Date FY: 2014 ( Subtotal = $127,683 )
2014	2014	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Blood Diseases and Resources Research	002	5	8/1/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$127,683
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Blood Diseases and Resources Research	001	4	7/31/2014	NON-COMPETING CONTINUATION	-$131,571
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Blood Diseases and Resources Research	000	4	6/30/2014	NON-COMPETING CONTINUATION	$131,571
														Subtotal = $127,683

Issue Date FY: 2013 ( Subtotal = $131,571 )
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Blood Diseases and Resources Research	000	3	6/13/2013	NON-COMPETING CONTINUATION	$131,571
														Subtotal = $131,571

Issue Date FY: 2012 ( Subtotal = $131,571 )
2012	2012	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Blood Diseases and Resources Research	000	2	5/30/2012	NON-COMPETING CONTINUATION	$131,571
														Subtotal = $131,571

Issue Date FY: 2011 ( Subtotal = $131,571 )
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Blood Diseases and Resources Research	000	1	9/5/2011	NEW	$131,571
														Subtotal = $131,571

Grand Total All Awards = $648,627

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Plerixafor for allogeneic hematopoietic stem cell transplantation

Award Number: K08HL103780

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2014

PERIOD OF PERFORMANCE END DATE: 06/30/2016

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