title: Allogeneic hematopoietic stem cell transplantation for nonmalignant hematologic disorders using chemotherapy-only cytoreductive regimens and T-cell-depleted grafts from human leukocyte antigen-matched or -mismatched donors.
abstract: Nonmalignant hematologic disorders (NMHD) of childhood comprise a variety of disorders, including acquired severe aplastic anemia and inherited marrow failure syndromes. Patients with high-risk NMHD without matched related donors fare poorly with allogeneic hematopoietic alternative donor stem cell transplantation (allo-HSCT) and are at high risk for developing graft-versus-host disease following unmodified grafts. The authors retrospectively analyzed data on 18 patients affected by NMHD, lacking a human leukocyte antigen (HLA)-identical sibling donor, who underwent an alternative donor allo-HSCT at their institution between April 2005 and May 2013. Fifty percent of the patients had received prior immunosuppressive therapy, 72% had a history of infections, and 56% were transfusion dependent at the time of transplant. Cytoreduction included a combination of 3 of 5 agents: fludarabine, melphalan, thiotepa, busulfan, and cyclophosphamide. Grafts were T-cell depleted. All evaluable patients engrafted. Five died of transplant complications. The cumulative incidence of graft-versus-host disease was 6%. No patient had recurrence of disease. Five-year overall survival was 77%. Age at transplant <6 years was strongly associated with better survival. Based on these results, transplant with chemotherapy-only cytoreductive regimens and T-cell-depleted stem cell transplants could be recommended for patients with high-risk NMHD, especially at a younger age.
authors.affiliation: a Dipartimento di Ematologia e Onco-Ematologia Pediatrica , Fondazione IRCCS Istituto Nazionale dei Tumori , Milan , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mussetti
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Kernan
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Prockop
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Andromachi
authors.initials: A
authors.lastname: Scaradavou
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lehrman
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Julianne M
authors.initials: JM
authors.lastname: Ruggiero
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Curran
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kobos
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.
authors.forename: Richard
authors.initials: R
authors.lastname: O'Reilly
authors.affiliation: b Bone Marrow Transplant Service, Department of Pediatrics , Memorial Sloan Kettering Cancer Center , New York , New York , USA.|c Division of Pediatric Hematology/Oncology , New York Presbyterian Hospital, Weill Cornell Medical College , New York , New York , USA.
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
mesh_terms: D000293:Adolescent; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000628:therapy; D006402:Hematologic Diseases / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage; D015996:Survival Rate; D013601:T-Lymphocytes; D019172:Transplantation Conditioning; D061349:Unrelated Donors
chemical_list: D019653:Myeloablative Agonists
keywords: Anemias; bone marrow failure; bone marrow transplant; chemotherapy