Myeloid reconstruction: Cord blood progenitors offer rapid results but labor-intensive technique

SAN FRANCISCO -- A new technique to expand cord blood cells has demonstrated mixed results with myeloid engraftment in patients achieved in an average of 16 days. But results from the preliminary clinical trial indicate that the technique is logistically cumbersome and will most likely require modification before it can be a viable alternative for patients, according to Seattle-based investigators.

The technique used the Delta1 ligand to expand CD34+ cells in cultures of cord blood. In the trial, 10 patients with acute myeloid leukemia or acute lymphoblastic leukemia were treated with a transplantation preparation regimen of cyclophosphamide (120 mg/kg), fludarabine (75 mg/m2), and TBI (1320 cGy), followed one day later by an infusion of one unit of non-cultured cored blood and one unit that had been CD34+ enriched and cultured for 16 days (abstract #212).

A control group of 17 patients underwent an identical transplant regimen, but received two non-cultured cord blood units. The researchers hoped that the expansion technique might improve outcomes in transplantation with umbilical cord cells, and make it a safer alternative for patients who cannot find a matched donor, explained Coleen Delaney, MD, of the Fred Hutchinson Cancer Research Center.

After infusion, the experimental group achieved myeloid engraftment in an average of 16 days compared to 25 days for the patients in the control group. The researchers were also able to demonstrate that one week post-transplant, the myeloid recovery in the experimental group came entirely from the expanded unit.

"It was quite remarkable, and resulted in a significant increase in the CD34+ stem cell dose that each patient received," Dr. Delaney said. Although the manipulated cells were merely meant to aid in rapid neutrophil recovery, helping to reduce regimen-related toxicity, two patients have shown long-term persistence of the expanded cells up to six months.

At present, nine patients remain in remission with little toxicity from their treatment, Dr. Delaney said. One patient in the experimental group died on day 462 from a rare complication of myelitis caused by the varicella-zoster virus.

Dr. Delaney noted that her group is now considering changes in their technique to make it less labor-intensive. "There's a lot of work involved before we can establish this as a routine transplantation method," she said. The present technique used previously cryopreserved cord blood tissues that were then thawed. Stem cells were then selected and placed in culture. Another alternative would be to start with fresh cord blood units, expand the stem cells, and then freeze the end product.

"That would give us a product and a technology that could be more readily available to patients," Dr. Delaney said.