title: Direct intrabone transplant of unrelated cord-blood cells in acute leukaemia: a phase I/II study.
abstract: BACKGROUND
  Cord-blood transplants are associated with delayed or failed engraftment in about 20% of adult patients. The aim of this phase I/II study was to establish the safety and efficacy of a new administration route (intrabone) for cord-blood cells, measured by the donor-derived neutrophil and platelet engraftment.
  
  
  METHODS
  Adult patients with acute leukaemia, for whom an unrelated stem-cell transplantation was indicated and no suitable unrelated human leucocyte antigen (HLA)-matched donor had been identified, were included in the study and underwent a cord-blood transplant in San Martino Hospital, Genoa, Italy. Eight patients were in first complete remission, ten in second complete remission, and 14 had advanced-stage, refractory disease. HLA matching was 5/6, 4/6, and 3/6 for 9, 22, and one patient, respectively. Cord-blood cells were concentrated in four 5-mL syringes, and were infused in the superior-posterior iliac crest under rapid general anaesthesia. Median transplanted cell dose was 2.6 x 10(7)/kg (range 1.4-4.2). The primary endpoint was the probability of neutrophil and platelet recovery after intrabone cord-blood transplantantion. Secondary endpoints included the incidence of acute graft-versus-host disease, relapse, and overall survival. This trial is registered on the ClinicalTrials.gov website, number NCT 00696046.
  
  
  RESULTS
  Between March 31, 2006, and Jan 25, 2008, 32 consecutive patients with acute myeloid leukaemia (n=20) or acute lymphoblastic leukaemia (n=12) underwent a cord-blood transplant (median age 36 years [range 18-66]). No complications occurred during or after the intrabone infusion of cells. Four patients with advanced-stage disease died within 12 days of the procedure. Median time to recovery of neutrophils in 28 patients (>/=0.5 x 10(9)/L) was 23 days (range 14-44) and median time to recovery of platelets in 27 patients (>/=20 x 10(9)/L) was 36 days (range 16-64). All patients were fully chimeric from 30 days after transplantation to the last follow-up visit, suggesting an early complete donor engraftment. No patient developed grade III-IV acute graft-versus-host disease. Causes of death were transplant related (n=5), infection (n=7), and relapse (n=4). 16 patients were alive and in haematological remission at a median follow-up of 13 months (range 3-23).
  
  
  CONCLUSIONS
  Our preliminary data suggest that direct intrabone cord-blood transplantation overcomes the problem of graft failure even when low numbers of HLA-mismatched cord-blood cells are transplanted, thus leading to the possibility of use of this technique in a large number of adult patients.
authors.affiliation: Stem Cells and Cell Therapy Centre, San Martino Hospital, Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Marina
authors.initials: M
authors.lastname: Podestà
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Raiola
authors.forename: Adalberto
authors.initials: A
authors.lastname: Ibatici
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piaggio
authors.forename: Mario
authors.initials: M
authors.lastname: Sessarego
authors.forename: Nadia
authors.initials: N
authors.lastname: Sessarego
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Sacchi
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D017148:Infusions, Intraosseous; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D014184:Transplantation, Homologous; D016896:Treatment Outcome