Allogeneic Hematopoietic Stem-Cell Transplantation for Sickle Cell Disease

• Published in: The New England journal of medicine Vol. 361; no. 24; pp. 2309 - 2317
• Main Authors: Hsieh, Matthew M, Kang, Elizabeth M, Fitzhugh, Courtney D, Link, M. Beth, Bolan, Charles D, Kurlander, Roger, Childs, Richard W, Rodgers, Griffin P, Powell, Jonathan D, Tisdale, John F
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 10.12.2009
• Subjects: Adolescent; Adult; Alemtuzumab; Anemia, Sickle Cell - therapy; Anemias. Hemoglobinopathies; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - therapeutic use; Antigens, CD34; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Bone marrow; Clinical Protocols; Disease; Diseases of red blood cells; Female; Follow-Up Studies; General aspects; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hemoglobins - analysis; Histocompatibility Testing; Humans; Leukocyte Count; Lymphocytes; Male; Medical sciences; Middle Aged; Mortality; Narcotics - adverse effects; Neutrophils; Sickle cell anemia; Sickle cell disease; Sirolimus - adverse effects; Sirolimus - therapeutic use; Stem cells; Substance Withdrawal Syndrome; Transplantation Chimera; Transplantation Conditioning - methods; Transplantation, Homologous; Transplants & implants; Whole-Body Irradiation; Young Adult; Medicine; Hemoglobinopathy; Hemolytic anemia; Sickle cell anemia; Allogeneic hematopoietic stem cell transplantation; Stem cell; Hematopoietic cell; Homograft; Graft; Hemopathy; Genetic disease
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0904971

A modified conditioning protocol for allogeneic hematopoietic stem-cell transplantation that does not ablate the bone marrow was used to treat 10 adults who had severe sickle cell disease. The sickle cell phenotype was eliminated in 9 of the 10 recipients. No deaths, no major adverse events, and no graft-versus-host disease occurred among the recipients. A protocol for allogeneic hematopoietic stem-cell transplantation that does not ablate the bone marrow was used to treat 10 adults who had severe sickle cell disease. The sickle cell phenotype was eliminated in 9 of the 10 recipients. Sickle cell disease results from a single nucleotide substitution in which valine replaces glutamic acid at the sixth position of the β-globin chain of hemoglobin A. 1 , 2 This change causes a propensity toward polymerization of hemoglobin and, hence, sickle-shaped red cells. Anemia, increased hemolysis, and acute and chronic vaso-occlusive complications that affect multiple organs are the main features of sickle cell disease. At present, allogeneic hematopoietic stem-cell transplantation is the only curative option. 3 – 5 Approximately 200 children have undergone this procedure after myeloablative conditioning with busulfan and cyclophosphamide, with or without antithymocyte globulin, resulting in a rate of disease-free survival . . .