Dr. Colleen Delaney of the Center’s Clinical Research Division presented preliminary data on her pioneering work using expanded cord-blood units for transplantation during the annual meeting of the American Society of Hematology. A media briefing on Sunday preceded the Dec. 8 annual meeting in San Francisco.
Delaney’s ongoing phase 1 clinical trial found that cord blood that is cultured to increase the number of CD34+ stem cells prior to transplantation helped to decrease the time to engraftment in patients with acute myeloid leukemia.
Cord blood is a valuable source of hematopoietic stem cells as it has a higher concentration of these cells than is normally found in adult blood. However, as only a small quantity of blood can typically be obtained from an umbilical cord, resulting in fewer available stem cells for transplantation, researchers have been investigating novel methods to expand the number of stem cells available from cord blood to help increase the success rates of cord blood stem cell transplants.
The objective of this study is to evaluate the safety and potential efficacy of giving increased numbers of cord blood progenitor cells that have been generated through a novel methodology whereby CD34+ cord blood progenitor cells are cultured prior to infusion to rapidly multiply in order to decrease the time required for the transplanted cells to engraft and begin production of healthy blood cells.
A total of nine patients with acute myeloid leukemia were treated with a transplantation-preparation regimen of cytoxan (120 mg/kg), fludarabine (75 mg/m2), and TBI (1320 cGy), followed one day later by an infusion of one unit of non-cultured cord blood and one unit of cord blood that had been CD34+ enriched and cultured for 16 days. The non-cultured unit was given to provide long-term repopulating stem cells that had not been previously manipulated, while the goal of the expanded unit was to provide cells capable of rapid myeloid recovery.
To achieve best results, cord blood units that most closely genetically matched the patient were selected for transfusion. All non-cultured cord blood stem cells were matched for four out of six alleles for each patient. For the cultured cord blood cells, some patients received a five-out-of-six allele match and some patients received a four-out-of-six allele match. There was an average CD34+ increase of 160 (range 41 to 382), meaning that for every one CD34+ cell, there were 160 CD34+ cells after the culture, with an average total nucleated cell fold increase of 660 (range 146 to 1496). A control group of 17 patients underwent an identical transplant regimen, but received two non-cultured cord-blood units.
A relatively rapid engraftment time, averaging 14 days, was observed in the nine patients in the experimental group compared with 25 days for the patients in the control group. The contribution of the expanded and non-cultured cord blood cells was determined by a DNA-based assay beginning seven days following the transplant. In the five patients with early engraftment, the engrafted cells present at day seven were derived almost entirely from the cultured unit. Persistent contribution to engraftment from the cultured cells was noted in two patients. One patient had persistent contribution from the cultured cells through 280 days post-transplant that was no longer noticeable at one year, and the second patient continued to demonstrate contribution from the cultured cells at 180 days post-transplant. One patient died on day 462 from a rare complication of myelitis (inflammation of the spinal cord) caused by the varicella-zoster virus, while all other patients were still in remission.
[Adapted from ASH news release]