title: Phase II study of unrelated cord blood transplantation for adults with high-risk hematologic malignancies.
abstract: Cell dose is a critical determinant of outcomes in unrelated cord blood (CB) transplantation. We investigated a strategy in which CB units should contain at least 2 x 10(7) total nucleated cells/kg of recipient weight, otherwise a second unit had to be added. We report the results of a study that was prematurely closed owing to toxicity. Patients with advanced hematologic malignancies without a human leukocyte antigen-matched sibling or unrelated donor were eligible. Conditioning regimen consisted of fludarabine and 12 Gy of total body irradiation (n=11), or melphalan (n=4), with antithymocyte globulin. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Fifteen patients with acute leukemia (n=9), chronic myelogenous leukemia (n=2), multiple myeloma (n=2) and lymphoma (n=2) were treated; 60% had relapsed disease at transplantation. Three patients received double CB transplants. The 100-day and 1-year treatment-related mortality rates were 40 and 53%, respectively. Median time to neutrophil and platelet engraftment was 22 days (n=10) and 37 days (n=10), respectively. One patient had secondary graft failure and five patients failed to engraft. Two patients are alive and disease free; 4-year actuarial survival is 33 versus 0% for patients transplanted in remission versus in relapse. We concluded that disease status was the main determinant of treatment failure in this study.
authors.affiliation: Department of Blood and Marrow Transplantation, UT MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lekakis
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: D
authors.initials: D
authors.lastname: Couriel
authors.forename: E J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: C
authors.initials: C
authors.lastname: Hosing
authors.forename: I F
authors.initials: IF
authors.lastname: Khouri
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: T
authors.initials: T
authors.lastname: Martin
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
authors.forename: M
authors.initials: M
authors.lastname: de Lima
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects; D036101:Cord Blood Stem Cell Transplantation / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000401:mortality; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D016559:Tacrolimus; D008727:Methotrexate