Dosing regimens for the mobilization of hematopoietic stem cells

Abstract

Described herein are compositions and methods useful for mobilizing populations of hematopoietic stem and progenitor cells within a subject, as well as for determining whether samples of mobilized cells are suitable for release for ex vivo expansion and/or therapeutic use. In accordance with the composition and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various disorders, including hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others.

What is claimed is: 
     
         1 . A method of mobilizing a population of hematopoietic stem cells from the bone marrow of a mammalian donor into peripheral blood, the method comprising administering to the donor (i) a CXCR2 agonist selected from the group consisting of Gro-β, Gro-β T, and variants thereof at a dose of from about 50 μg/kg to about 300 μg/kg and (ii) a CXCR4 antagonist. 
     
     
         2 . The method of  claim 1 , wherein the CXCR2 agonist is Gro-β T. 
     
     
         3 . The method of  claim 1 , wherein the CXCR2 agonist is administered to the donor at a dose of from about 100 μg/kg to about 250 μg/kg. 
     
     
         4 . The method of  claim 3 , wherein the CXCR2 agonist is administered to the donor at a dose of from about 125 μg/kg to about 225 μg/kg. 
     
     
         5 . The method of  claim 4 , wherein the CXCR2 agonist is administered to the donor at a dose of about 150 μg/kg. 
     
     
         6 . The method of  claim 1 , wherein the CXCR2 agonist is administered intravenously to the donor. 
     
     
         7 . The method of  claim 1 , wherein the CXCR4 antagonist is administered subcutaneously to the donor. 
     
     
         8 . The method of  claim 1 , wherein the CXCR4 antagonist is plerixafor or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 8 , wherein the plerixafor or pharmaceutically acceptable sat thereof is administered to the donor at a dose of from about 50 μg/kg to about 500 μg/kg. 
     
     
         10 . The method of  claim 9 , wherein the plerixafor or pharmaceutically acceptable sat thereof is administered to the donor at a dose of from about 200 μg/kg to about 300 μg/kg. 
     
     
         11 . The method of  claim 10 , wherein the plerixafor or pharmaceutically acceptable sat thereof is administered to the donor at a dose of about 240 μg/kg. 
     
     
         12 . A method of mobilizing a population of hematopoietic stem cells from the bone marrow of a mammalian donor into peripheral blood, the method comprising administering to the donor a CXCR2 agonist and a CXCR4 antagonist in amounts sufficient to produce a population of cells having a ratio of CD34+ cells to leukocytes of from about 0.0008 to about 0.0021 in a sample of peripheral blood of the donor following administration of the CXCR2 agonist and CXCR4 antagonist. 
     
     
         13 . The method of  claim 12 , wherein the ratio of CD34+ stem cells to leukocytes in the sample is from about 0.001 to about 0.0021. 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 12 , wherein the peripheral blood of the donor is enriched with CD34+ cells relative to leukocytes by a ratio of from about 3.4:1 to about 6.9:1. 
     
     
         16 . A method of mobilizing a population of hematopoietic stem cells from the bone marrow of a mammalian donor into peripheral blood, the method comprising administering to the donor a CXCR2 agonist and a CXCR4 antagonist in amounts sufficient to produce a population of cells having a ratio of CD34+ cells to neutrophils of from about 0.0018 to about 0.0058 in a sample of peripheral blood of the donor following administration of the CXCR2 agonist and CXCR4 antagonist. 
     
     
         17 . The method of  claim 16 , wherein the ratio of CD34+ cells to neutrophils in the sample is from about 0.0026 to about 0.0046. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 16 , wherein the peripheral blood of the donor is enriched with CD34+ cells relative to neutrophils by a ratio of from about 1:1 to about 1:1. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 16 , wherein the ratio of CD34+ cells to lymphocytes in the sample is from about 0.0021 to about 0.0094. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 16 , wherein the peripheral blood of the donor is enriched with CD34+ cells relative to lymphocytes by a ratio of from about 4.8:1 to about 4:1. 
     
     
         24 - 150 . (canceled)