Articulo sobre el doble transplante de cordon umbilical...

Umbilical Cord Blood Transplantation Program
Transplantation for Adult Patients

The University of Minnesota, under the leadership of Drs. Claudio Brunstein, Assistant Professor in the Department of Medicine, and John E. Wagner, Scientific Director of Clinical Research for the Adult and Pediatric Blood and Bone Marrow Transplant Program, is currently investigating a number of new transplant approaches using umbilical cord blood in adults. Umbilical cord blood offers several advantages over bone marrow for use in adults, most notably:

• Faster availability of unrelated donor umbilical cord blood as compared to bone marrow (1 day versus 3 months on average). This is important for patients who require urgent transplant due to potential risk of infection or rapid progression of disease.
• The tissue type match between the patient and the umbilical cord blood donor does not have to be perfect (i.e. 1-2 HLA mismatch is tolerated). Therefore, umbilical cord blood offers the potential to extend the opportunity of transplantation to those patients who cannot find a HLA matched unrelated bone marrow donor.
• Reduced incidence and severity of graft-versus-host disease. This has clearly been demonstrated in children and adults.

Until recently, there were some unique problems to be overcome in the transplantation of adults using umbilical cord blood. We know that the number of stem cells in cord blood (i.e. the cell dose) has a very important effect on survival after transplant. For larger teenagers and adults, a single cord blood unit often does not contain enough stem cells to perform the transplant safely. Therefore, we investigated transplantation of two closely HLA matched cord blood units or double umbilical cord blood transplant as a way to increase the number of cord blood stem cells transplanted. Investigators at the University of Minnesota were the first to investigate the feasibility, safety and efficacy of mixing two closely HLA matched UCB units. This novel treatment has opened up cord blood transplants to patients as never before and has gotten worldwide attention. The results were better than expected.

• Recovery of the blood and marrow is now highly likely in adults in contrast to past results with a single cord blood unit.
• Severe GVHD remains low despite 2 antigen mismatching.
• Survival exceeds 70% at 1 year for patients in remission and who received a full preparative therapy.
• Relapse is less than 10% for those transplanted in remission.

In addition to speeding recovery of white cells, results so far suggest that double UCB transplantation in adults is associated with a lower risk of relapse possibly because there are two healthy immune systems capable of rejecting the leukemia or tumor cells.
In addition, we know that 1) older adult patients, 2) those that have relapsed after a prior transplant, 3) those that have already had extensive therapy for their cancer, or 4) those who have other illnesses or complications, will not be strong enough to undergo high dose chemotherapy and radiation. Therefore, we are investigating a non-myeloablative preparative therapy that still enables the growth of the umbilical cord blood cells in the body. These transplants are designed to be less toxic and are effective by means of an immunological effect of the umbilical cord blood cells attacking cancer cells known as the "graft-versus-malignancy" effect. This study represents another first for the University of Minnesota investigators' breakthrough work.
The first clinical trial to investigate the feasibility, safety and efficacy of umbilical cord blood after non-myeloablative preparative regimen has enrolled more than 120 patients and represents one of the fastest enrolling trials at the Masonic Cancer Center.
Early results are very encouraging in that:

• Engraftment of UCB has been observed in most patients (> 90%) at an average of 8 days.
• Toxicity of this regimen is less than conventional transplants.

New studies for 2005:

• Co-infusion of Regulatory T cells to enhance engraftment, speed recovery, further reduce the risk of GVHD (clinical trial opened in June 2005).
• Intra bone marrow of UCB to enhance engraftment and speed of recovery (clinical trial opened in February 2005).