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Blood First Edition Paper, prepublished online November 6, 2009; DOI 10.1182/blood-2009-05-218982.
Submitted May 5, 2009; accepted October 1, 2009.
Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia1 International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy; 2 Tor Vergata University and the Immunohematology Section, Bambino Gesu Pediatric Hospital, Rome, Italy; 3 Servizio di Immunoematologia e Medicina Trasfusionale, Policlinico Tor Vergata, Rome, Italy; 4 Meyer Children's Hospital, Florence, Italy; 5 LIBT, International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy * Corresponding author; email: p.sodani{at}fondazioneime.org Abstract Feto-maternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem-cell transplantation (HSCT) from mismatched mother to thalassemic patient without an HLA-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/m2 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 anti-thymocyte globulin daily from day -5 to -2. Fourteen patients received CD34+ mobilized peripheral and bone marrow progenitor cells; eight patients received marrow graft selected PBSC CD34+ and BM CD3/CD19 depleted . T-cell dose was adjusted to 2 x 105/kg by fresh marrow cell addback at the time of transplant. Both groups received cyclosporine for graft versus host disease (GVHD) prophylaxis for two months post transplant. Two patients died (cerebral EBV lymphoma or CMV pneumonia), six 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 GVHD. These results suggest that maternal haploidentical HSCT is feasible for patients with thalassemia who lack a matched related donor.
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