title: Total lymphoid irradiation-antithymocyte globulin conditioning and allogeneic transplantation for patients with myelodysplastic syndromes and myeloproliferative neoplasms.
abstract: Allogeneic hematopoietic cell transplantation (allo HCT) is the only curative therapy for the myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but treatment toxicity has been a barrier to its more widespread use. The nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) permits the establishment of donor hematopoiesis necessary for the graft-versus-malignancy effect and is protective against acute graft-versus-host disease (aGVHD), but it has minimal direct cytotoxicity against myeloid diseases. We explored the use of TLI-ATG conditioning to treat 61 patients with allo HCT for MDS (n = 32), therapy-related myeloid neoplasms (n = 15), MPN (n = 9), and chronic myelomonocytic leukemia (n = 5). The median age of all patients was 63 years (range, 50 to 73). The cumulative incidence of aGVHD grades II to IV was 14% (95% confidence interval [CI], 4% to 23%) and for grades III to IV, 4% (95% CI, 0 to 9%), and it did not differ between patients who received allografts from related or unrelated donors. The cumulative incidence of nonrelapse mortality (NRM) at 100 days, 12 months, and 36 months was 0%, 7%, and 11%. Overall survival and progression-free survival were 41% (95% CI, 29% to 53%) and 35% (95% CI, 23% to 48%), respectively. The safety and tolerability of TLI-ATG, as exemplified by its low NRM, provides a foundation for further risk-adapted or prophylactic interventions to prevent disease progression.
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Benjamin
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Chhabra
authors.affiliation: Division of Oncology, Stanford University, Stanford, California.
authors.forename: Holbrook E
authors.initials: HE
authors.lastname: Kohrt
authors.affiliation: Department of Health Research and Policy, Stanford University, Stanford, California.
authors.forename: Philip
authors.initials: P
authors.lastname: Lavori
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Sally
authors.initials: S
authors.lastname: Arai
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Laura
authors.initials: L
authors.lastname: Johnston
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Weng
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.affiliation: Division of Blood and Marrow Transplantation, Stanford University, Stanford, California. Electronic address: rlowsky@stanford.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Lowsky
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015182:Lymphatic Irradiation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D009196:Myeloproliferative Disorders / Q000628:therapy*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum
keywords: Myelodysplastic syndrome; Myeloproliferative neoplasm; Nonmyeloablative conditioning