Intrabone transplant provides full stemness of cord blood stem cells with fast hematopoietic recovery and low GVHD rate: results from a prospective study

Francesca Bonifazi, Elisa Dan, Myriam Labopin, Mariarosaria Sessa, Viviana Guadagnuolo, Martina Ferioli, Simonetta Rizzi, Sabrina De Carolis, Barbara Sinigaglia, Maria Rosa Motta, Andrea Bontadini, Valeria Giudice, Giovanni Martinelli, Mario Arpinati, Michele Cavo, Massimiliano Bonafé, Gianluca Storci

Research output: Contribution to journalArticlepeer-review

Abstract

Umbilical Cord Blood (UCB) represents a valid option for patients with hematopoietic malignancies lacking an HLA matched donor. To overcome the limitation of the low stem cell dose of UCB, the intrabone (IB) route has been proposed. We report the results of a prospective study on a poor-prognosis cohort of 23 patients receiving intrabone single UCB transplant (Clinicaltrials.gov NCT00886522). Cumulative incidence of hematological recovery at day 90 was 82 ± 9% (ANC > 0.5 × 109/L) and 70 ± 10% (platelet > 50 × 109/L) and correlated with CD34 + cells in the graft. NRM was 20 ± 9%. No severe aGVHD and only one extensive cGVHD occurred, with fast immune reconstitution. To test the hypothesis that the direct IB injection could affect the expression of stem cells regulatory pathways, CD34 + cells from BM aspirates at day + 10, + 20, + 30, processed in hypoxic conditions mimicking the BM-microenvironment (7%pO2), were studied for the expression of c-Mpl, Notch1 and CXCR4. We found that the expression of c-Mpl in CD34 + cells at day + 10 significantly correlated with hematological recovery. In conclusion, IB-UCB transplant success is associated with low incidence of GVHD and high-speed platelet recovery; intrabone route may preserve full hematopoietic stemness by direct delivery of UCB stem cells into the hypoxic HSC niche.

Original languageEnglish
JournalBone Marrow Transplantation
DOIs
Publication statusAccepted/In press - Jan 1 2018

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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