Intra Bone Marrow Injection Of Unrelated Cord Blood Cells

Summary

Compared to other stemcell sources cord blood (CB) is easier and safer to procure, has no donor attrition, a limitless supply, reduced viral transmission, less acute \& chronic GVHD, is rich in hematopoietic progenitor cells, and immaturity of T-cell-mediated immunity. CB has delayed neutrophil and platelet engraftment, a prolonged immune reconstitution, uncertain graft-vs-tumor activity, and cell doses from single CB units (U) are a limiting factor for larger recipients Using the intravenous route (IV), a close match between the patient (pts) and the donor or CBU can improve a pts outcome after transplant. Even though a closely matched CBU is preferred, the studies suggest the match may not have to be as close as is needed for marrow or peripheral blood transplants If one has an uncommon tissue type, the doctor may not find a closely matched adult donor and a CBU may be an option, are stored and ready to use. GVHD is a complication after an allogeneic transplant. Studies founded that after a CBtransplant, fewer pts get GVHD than after marrow or peripheral blood transplants. Pts in the studies who did get GVHD after CBtransplant tended to get less severe cases We hypothesized that direct intrabone transplant of CBcells could improve haematologic recovery due to a better stem cell homing, based on the following observations: stem cells recirculate in animals irradiated with limb shielding; a limited fraction (10-15%) of cells injected iv to the haematopoietic sites, possibly because the large majority is lost in other organs; in a mousemodel, HSC directly injected ib repopulated the marrow of lethally irradiated mice 10times more efficiently than HSC cells injected iv; delayed engraftment after CB transplant is possibly not caused by insufficient stem cell numbers; indeed, children grafted with CB cells have superior stem cell reservoir 1year posttransplant when compared to marrow transplant recipients Based on these data, we set-up a phase I-II study to evaluate whether ib injection could be safely performed and whether this procedure could ensure engraftment and shorten the time of complete hematopoietic recovery in adults with high risk haematopoietic malignancies compared to the published data. Neutrophil recovery \>80% at day60 and Platelets recovery \>80% at days100 were defined as success. 1° endpoint was the probability of neutrophils and platelets recovery after ib CB transplant, 2° included incidence of acute GVHD, relapse, overall survival

Conditions

• Hematologic Diseases

Interventions

PROCEDURE

Intrabone Marrow Injection

Cord blood CB units will be thawed in a 37° CB cells will be resuspended in 20ml salinesolution + dextran/albumin, and aliquoted in 4 syringes of 5ml Pts were prepared in a surgical \& steril room The anaesthesia consist in a short propofol sedation The injection will last 8-15 minutes. 1° sedation is established, a standard needle for bone marrow aspiration (14 gauge) was inserted few cms in the supero-posterior iliac crest then, an aspiration of about 0.5-1 ml will be performed to assess that the needle was securely introduced in the bone marrow cavity After, we will insert the syringe containing 4-5ml of CB cell suspension which will be gently infused This procedure will be then repeated for all the remaining aliquots at a distance of 2-3cm from the previous one following the iliac crest

Sponsors & Collaborators

• IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

  lead OTHER

Principal Investigators

• francesco frassoni, MD · A.O. San martino

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

16 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-03-31

Primary Completion

2008-12-31

Completion

2009-06-30

Countries

• Italy

Study Locations