title: Mismatched T cell-depleted hematopoietic stem cell transplantation for children with high-risk acute leukemia.
abstract: The aim of this study was to extend allogeneic hematopoietic stem cell transplantation to leukemia patients without a matched donor. To prevent graft failure, large doses of T cell-depleted hematopoietic stem cells were transplanted following a highly myeloablative and immunosuppressive conditioning regimen. Fifteen children with high-risk acute leukemia received T cell-depleted hematopoietic stem cells from full-haplotype mismatched family members after a conditioning regimen that included single-dose TBI, thiotepa, ATG and fludarabine. To prevent GVHD, marrow cells were T-depleted by soybean agglutinin and E-rosetting, peripheral blood cells by E-rosetting followed by positive selection of the CD34+ cells. No post-transplant prophylaxis for GVHD was administered. In all patients full donor-type engraftment was achieved. None of the evaluable patients developed either acute or chronic GVHD. Regimen-related toxicity was minimal. Five patients are alive and event-free at a median follow-up of 18 months (range 13-28). All surviving patients have a good quality of life. Seven patients have relapsed. This study shows that GVHD and graft failure, which limited the use of full-haplotype mismatched bone marrow transplants, have been overcome. Since almost all children have a mismatched relative, advances in this area should make mismatched transplants a routine consideration for patients with high-risk leukemia without a matched related or unrelated donor.
authors.affiliation: Section of Hematology and Clinical Immunology, University of Perugia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Aversa
authors.forename: A
authors.initials: A
authors.lastname: Terenzi
authors.forename: R
authors.initials: R
authors.lastname: Felicini
authors.forename: A
authors.initials: A
authors.lastname: Tabilio
authors.forename: F
authors.initials: F
authors.lastname: Falzetti
authors.forename: A
authors.initials: A
authors.lastname: Carotti
authors.forename: F
authors.initials: F
authors.lastname: Falcinelli
authors.forename: P
authors.initials: P
authors.lastname: Sodani
authors.forename: A
authors.initials: A
authors.lastname: Amici
authors.forename: P
authors.initials: P
authors.lastname: Zucchetti
authors.forename: I
authors.initials: I
authors.lastname: Mazzarino
authors.forename: M F
authors.initials: MF
authors.lastname: Martelli
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects