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accordance with the composition and methods described herein, mobilized hematopoietic stem and progenitor cells can be withdrawn from a donor and administered to a patient for the treatment of various disorders, including hematopoietic diseases, metabolic disorders, cancers, and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 .- 115 . (canceled) 
     
     
         116 . A method of treating a stem cell disorder in a human patient, the method comprising infusing into the patient a therapeutically effective amount of hematopoietic stem cells or progeny thereof mobilized by a method comprising:
 administering to a human donor (i) Gro-β T at a dose of about 150 μg/kg, wherein the Gro-β T is administered intravenously to the donor and (ii) about 240 μg/kg plerixafor or a pharmaceutically acceptable salt thereof, wherein the plerixafor or pharmaceutically acceptable salt thereof is administered subcutaneously to the donor.   
     
     
         117 .- 118 . (canceled) 
     
     
         119 . The method of  claim 116 , wherein the stem cell disorder is a hemoglobinopathy disorder selected from the group consisting of sickle cell anemia, thalassemia, Fanconi anemia, aplastic anemia, and Wiskott-Aldrich syndrome. 
     
     
         120 . The method of  claim 116 , wherein the stem cell disorder is a myelodysplastic disorder. 
     
     
         121 . The method of  claim 116 , wherein the stem cell disorder is a congenital or acquired immunodeficiency disorder. 
     
     
         122 .- 123 . (canceled) 
     
     
         124 . The method of  claim 121 , wherein the acquired immunodeficiency is human immunodeficiency virus or acquired immune deficiency syndrome. 
     
     
         125 . (canceled) 
     
     
         126 . The method of  claim 116 , wherein the stem cell disorder is a metabolic disorder selected from the group consisting of glycogen storage diseases, mucopolysaccharidoses, Gaucher's Disease, Hurlers Disease, sphingolipidoses, and metachromatic leukodystrophy. 
     
     
         127 . (canceled) 
     
     
         128 . The method of  claim 116 , wherein the stem cell disorder is a cancer selected from the group consisting of leukemia, lymphoma, multiple myeloma, and neuroblastoma. 
     
     
         129 . (canceled) 
     
     
         130 . The method of  claim 128 , wherein the cancer is acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma, diffuse large B-cell lymphoma, or non-Hodgkin's lymphoma. 
     
     
         131 . The method of  claim 116 , wherein the stem cell disorder is a disorder selected from the group consisting of adenosine deaminase deficiency and severe combined immunodeficiency, hyper immunoglobulin M syndrome, Chediak-Higashi disease, hereditary lymphohistiocytosis, osteopetrosis, osteogenesis imperfecta, storage diseases, thalassemia major, systemic sclerosis, and systemic lupus erythematosus. 
     
     
         132 . (canceled) 
     
     
         133 . The method of  claim 116 , wherein the stem cell disorder is an autoimmune disorder selected from the group consisting of multiple sclerosis, human systemic lupus, rheumatoid arthritis, inflammatory bowel disease, treating psoriasis, Type 1 diabetes mellitus, acute disseminated encephalomyelitis, Addison's disease, alopecia universalis, ankylosing spondylitisis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune lymphoproliferative syndrome, autoimmune oophoritis, Balo disease, Behcet's disease, bullous pemphigoid, cardiomyopathy, Chagas' disease, chronic fatigue immune dysfunction syndrome, chronic inflammatory demyelinating polyneuropathy, Crohn's disease, cicatrical pemphigoid, coeliac sprue-dermatitis herpetiformis, cold agglutinin disease, CREST syndrome, Degos disease, discoid lupus, dysautonomia, endometriosis, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Goodpasture's syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, Hidradenitis suppurativa, idiopathic and/or acute thrombocytopenic purpura, idiopathic pulmonary fibrosis, IgA neuropathy, interstitial cystitis, juvenile arthritis, Kawasaki's disease, lichen planus, Lyme disease, Meniere disease, mixed connective tissue disease, myasthenia gravis, neuromyotonia, opsoclonus myoclonus syndrome, optic neuritis, Ord's thyroiditis, pemphigus vulgaris, pernicious anemia, polychondritis, polymyositis and dermatomyositis, primary biliary cirrhosis, polyarteritis nodosa, polyglandular syndromes, polymyalgia rheumatica, primary agammaglobulinemia, Raynaud phenomenon, Reiter's syndrome, rheumatic fever, sarcoidosis, scleroderma, Sjögren's syndrome, stiff person syndrome, Takayasu's arteritis, temporal arteritis, ulcerative colitis, uveitis, vasculitis, vitiligo, vulvodynia, and Wegener's granulomatosis. 
     
     
         134 . The method of  claim 116 , wherein the hematopoietic stem cells are autologous with respect to the patient. 
     
     
         135 . The method of  claim 116 , wherein the hematopoietic stem cells are allogeneic with respect to the patient. 
     
     
         136 . The method of  claim 116 , wherein the hematopoietic stem cells are HLA-matched with respect to the patient. 
     
     
         137 . The method of  claim 116 , wherein the hematopoietic stem cells have been genetically modified. 
     
     
         138 . The method of  claim 116 , wherein the endogenous gene encodes a major histocompatibility complex protein. 
     
     
         139 .- 144 . (canceled) 
     
     
         145 . The method of  claim 116 , further comprising isolating the hematopoietic stem cells or progeny thereof by drawing peripheral blood from the donor. 
     
     
         146 . The method of  claim 116 , further comprising using apheresis to collect the hematopoietic stem cells or progeny thereof from the donor. 
     
     
         147 . The method of  claim 116 , wherein the Gro-β T has a purity of at least about 95% relative to the deamidated versions of these peptides. 
     
     
         148 .- 150 . (canceled) 
     
     
         151 . The method of  claim 137 , wherein the hematopoietic stem cells have been genetically modified to disrupt an endogenous gene.