Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia.
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.
Sodani
Pietro
P
International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy. p.sodani@fondazioneime.org
Isgrò
Antonella
A
Gaziev
Javid
J
Polchi
Paola
P
Paciaroni
Katia
K
Marziali
Marco
M
Simone
Maria Domenica
MD
Roveda
Andrea
A
Montuoro
Aldo
A
Alfieri
Cecilia
C
De Angelis
Gioia
G
Gallucci
Cristiano
C
Erer
Buket
B
Isacchi
Giancarlo
G
Zinno
Francesco
F
Adorno
Gaspare
G
Lanti
Alessandro
A
Faulkner
Lawrence
L
Testi
Manuela
M
Andreani
Marco
M
Lucarelli
Guido
G
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
D018952:Antigens, CD34; D006680:HLA Antigens