title: Hematopoietic cell transplantation with cord blood for cure of HIV infections.
abstract: Hematopoietic cell transplantation (HCT) using CCR5-Δ32/Δ32 stem cells from an adult donor has resulted in the only known cure of human immunodeficiency virus (HIV) infection. However, it is not feasible to repeat this procedure except rarely because of the low incidence of the CCR5-Δ32 allele, the availability of only a small number of potential donors for most patients, and the need for a very close human leukocyte antigen (HLA) match between adult donors and recipients. In contrast, cord blood (CB) transplantations require significantly less stringent HLA matching. Therefore, our hypothesis is that cure of HIV infections by HCT can be accomplished much more readily using umbilical CB stem cells obtained from a modestly sized inventory of cryopreserved CCR5-Δ32/Δ32 CB units. To test this hypothesis, we developed a screening program for CB units and are developing an inventory of CCR5-Δ32/Δ32 cryopreserved units available for HCT. Three hundred such units are projected to provide for white pediatric patients a 73.6% probability of finding an adequately HLA matched unit with a cell dose of ≥2.5 × 10(7) total nucleated cells (TNCs)/kg and a 27.9% probability for white adults. With a cell dose of ≥1 × 10(7) TNCs/kg, the corresponding projected probabilities are 85.6% and 82.1%. The projected probabilities are lower for ethnic minorities. Impetus for using CB HCT was provided by a transplantation of an adult with acute myelogenous leukemia who was not HIV infected. The HCT was performed with a CCR5-Δ32/Δ32 CB unit, and posttransplantation in vitro studies indicated that the patient's peripheral blood mononuclear cells were resistant to HIV infection.
authors.affiliation: StemCyte International Cord Blood Center, Covina, CA 91722, USA. lpetz@stemcyte.com
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Petz
authors.forename: Istvan
authors.initials: I
authors.lastname: Redei
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Bryson
authors.forename: Donna
authors.initials: D
authors.lastname: Regan
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shpall
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gutman
authors.forename: Sergio
authors.initials: S
authors.lastname: Querol
authors.forename: Pamela
authors.initials: P
authors.lastname: Clark
authors.forename: Richard
authors.initials: R
authors.lastname: Tonai
authors.forename: Sarah
authors.initials: S
authors.lastname: Santos
authors.forename: Aide
authors.initials: A
authors.lastname: Bravo
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Loren
authors.initials: L
authors.lastname: Gragert
authors.forename: John
authors.initials: J
authors.lastname: Rossi
authors.forename: Shirley
authors.initials: S
authors.lastname: Li
authors.forename: Haitang
authors.initials: H
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
authors.forename: John
authors.initials: J
authors.lastname: Zaia
authors.forename: Joseph
authors.initials: J
authors.lastname: Rosenthal
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Robert
authors.initials: R
authors.lastname: Chow
mesh_terms: D000328:Adult; D001771:Blood Banks; D002478:Cells, Cultured; D002648:Child; D036101:Cord Blood Stem Cell Transplantation; D015925:Cryopreservation; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000821:virology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000821:virology; D011336:Probability; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D017384:Sequence Deletion; D018183:Transplantation Chimera / Q000276:immunology; D061349:Unrelated Donors; D044465:White People
chemical_list: D006680:HLA Antigens; D019713:Receptors, CCR5