title: Cord blood transplants: early recovery of neutrophils from co-transplanted sibling haploidentical progenitor cells and lack of engraftment of cultured cord blood cells, as ascertained by analysis of DNA polymorphisms.
abstract: The number of infused cells is a very important factor in cord blood transplant (CBT) engraftment. Prior ex vivo expansion of aliquots of transplanted cord blood (CB) units is being investigated as a procedure to increase engraftment potential, but results are difficult to evaluate due to a lack of markers for assessing the contribution of expanded cells. We transplanted five patients, infusing the best available CB unit and cells from a second donor simultaneously. In two patients, these cells were obtained from another frozen CB unit by CD34(+)positive selection and culture expansion; the other three patients received uncultured highly purified haploidentical CD34(+) cells. The first two patients had DNA from the culture expanded CB cells detected only for a few days around day +11 when the absolute neutrophil count (ANC) was >200/microl; thereafter and when the ANC was <500/microl, only donor DNA from the uncultured CB was detected. For the other three patients, DNA analysis showed early and transient granulocyte engraftment of haploidentical cells, progressively replaced by the CB-derived granulocytes. We concluded that: (1) simultaneous infusion of lymphocyte-depleted HLA highly mismatched haematopoietic progenitor cells has not produced unfavourable effects for CBT; (2) the double transplant model is suitable for evaluating the engraftment potential of ex vivocultured CB cells in the clinical setting; (3) the culture conditions used did not result in early recovery of ANC; and (4) co-transplantation of purified uncultured HLA haploidentical CD34(+) cells may reduce the time of neutropenia following CBT.
authors.affiliation: Servicio de Hematología, Clínica Puerta de Hierro, Universidad Autónoma de Madrid, Spain.
authors.forename: M N
authors.initials: MN
authors.lastname: Fernández
authors.forename: C
authors.initials: C
authors.lastname: Regidor
authors.forename: R
authors.initials: R
authors.lastname: Cabrera
authors.forename: J
authors.initials: J
authors.lastname: García-Marco
authors.forename: M
authors.initials: M
authors.lastname: Briz
authors.forename: R
authors.initials: R
authors.lastname: Forés
authors.forename: I
authors.initials: I
authors.lastname: Sanjuán
authors.forename: A
authors.initials: A
authors.lastname: McWhinnie
authors.forename: S
authors.initials: S
authors.lastname: Querol
authors.forename: J
authors.initials: J
authors.lastname: García
authors.forename: A
authors.initials: A
authors.lastname: Madrigal
mesh_terms: D000208:Acute Disease; D000328:Adult; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D009679:Nuclear Family; D011110:Polymorphism, Genetic / Q000235:genetics*; D018183:Transplantation Chimera / Q000235:genetics