title: Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia.
abstract: Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen-identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day -59 to -11; 30 mg/m(2) fludarabine from day -17 to -11; 14 mg/kg busulfan starting on day -10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.5 mg/kg antithymocyte globulin daily from day -5 to -2. Fourteen patients received CD34(+)-mobilized peripheral blood and bone marrow progenitor cells; 8 patients received marrow graft-selected peripheral blood stem cells CD34(+) and bone marrow CD3/CD19-depleted cells. T-cell dose was adjusted to 2 x 10(5)/kg by fresh marrow cell addback at the time of transplantation. Both groups received cyclosporine for graft-versus-host disease prophylaxis for 2 months after transplantation. Two patients died (cerebral Epstein-Barr virus lymphoma or cytomegalovirus pneumonia), 6 patients reject their grafts, and 14 showed full chimerism with functioning grafts at a median follow-up of 40 months. None of the 14 patients who showed full chimerism developed acute or chronic graft-versus-host disease. These results suggest that maternal haploidentical hematopoietic stem cell transplantation is feasible in patients with thalassemia who lack a matched related donor.
authors.affiliation: International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy. p.sodani@fondazioneime.org
authors.forename: Pietro
authors.initials: P
authors.lastname: Sodani
authors.forename: Antonella
authors.initials: A
authors.lastname: Isgrò
authors.forename: Javid
authors.initials: J
authors.lastname: Gaziev
authors.forename: Paola
authors.initials: P
authors.lastname: Polchi
authors.forename: Katia
authors.initials: K
authors.lastname: Paciaroni
authors.forename: Marco
authors.initials: M
authors.lastname: Marziali
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Simone
authors.forename: Andrea
authors.initials: A
authors.lastname: Roveda
authors.forename: Aldo
authors.initials: A
authors.lastname: Montuoro
authors.forename: Cecilia
authors.initials: C
authors.lastname: Alfieri
authors.forename: Gioia
authors.initials: G
authors.lastname: De Angelis
authors.forename: Cristiano
authors.initials: C
authors.lastname: Gallucci
authors.forename: Buket
authors.initials: B
authors.lastname: Erer
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Isacchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Zinno
authors.forename: Gaspare
authors.initials: G
authors.lastname: Adorno
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lanti
authors.forename: Lawrence
authors.initials: L
authors.lastname: Faulkner
authors.forename: Manuela
authors.initials: M
authors.lastname: Testi
authors.forename: Marco
authors.initials: M
authors.lastname: Andreani
authors.forename: Guido
authors.initials: G
authors.lastname: Lucarelli
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008212:Lymphocyte Depletion; D008875:Middle Aged; D009035:Mothers; D036102:Peripheral Blood Stem Cell Transplantation; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D013601:T-Lymphocytes; D013789:Thalassemia / Q000628:therapy*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D006680:HLA Antigens