Umbilical cord blood transplant alternative for older pts

February 1, 2008

While reduced-intensity conditioning allows hematopoietic stem cell transplant (HSCT) in older cancer patients who cannot tolerate standard conditioning regimens, only about one-third of such patients have an HLA-matched related donor available. For these patients, stem cells derived from unrelated umbilical cord blood (UCB) may provide a suitable and convenient alternative

ATLANTA—While reduced-intensity conditioning allows hematopoietic stem cell transplant (HSCT) in older cancer patients who cannot tolerate standard conditioning regimens, only about one-third of such patients have an HLA-matched related donor available. For these patients, stem cells derived from unrelated umbilical cord blood (UCB) may provide a suitable and convenient alternative. Navneet Majhail, MD, of the University of Minnesota, reported good results with UCB transplants at ASH 2007 (abstract 331).

The trial included 90 patients older than age 55 undergoing reduced-intensity conditioning HSCT between 2000 and 2005. The most common diagnosis was acute myelogenous leukemia/myelodysplastic syndrome. Approximately half of the patients (n = 47) received stem cells from a matched related donor (6/6 HLA-matched).

The remaining 43 patients, who had no 5/6 or 6/6 HLA-matched related donor, received a UCB regimen consisting of total-body irradiation (200 cGy) and either cyclophosphamide/fludarabine (n = 69), busulfan/fludarabine (n = 16), or busulfan/cladribine (n = 5).

Matched related donor and UCB transplants produced equivalent outcomes with respect to the primary endpoint of progression-free survival (PFS), as well as secondary endpoints of overall survival, treatment-related mortality, and acute graft-vs-host disease (GVHD).

For the matched related donor and UCB groups, 3-year PFS was 34% and 30%, respectively (P = .98); 3-year overall survival was 43% and 34% (P = .57), and treatment-related mortality was 23% and 28% (P = .36).

Cumulative incidence of sustained donor engraftment, measured at 6 weeks, was 100% for matched related donor transplants vs 89% for UCB (P = .05).

There were no significant differences for the matched donor and UCB arms in the incidence of grade 2-4 acute GVHD (42% vs 49%) or treatment-related mortality at day 180 (23% vs 28%). UCB recipients had a significantly lower incidence of chronic GVHD at 1 year (40% vs 17%, P = .02).

In multivariate analysis, only high (≥ 3) HSCT comorbidity index score was independently predictive of worse PFS, overall survival, and treatment-related mortality.

"The donor source (cord blood or matched related donor) had no effect on outcome," Dr. Majhail emphasized.

Further research should identify specific diseases in which unmatched UCB transplant may be indicated, Dr. Majhail said. Additionally, since less than 20% of adults are able to find a suitable single UCB match, the use of two cord bloods in such transplants is often required.

In an interview with ONI, John DiPersio, MD, Washington University School of Medicine, commented that the use of UCB can both reduce the incidence and severity of GVHD and increase the donor pool by allowing donors stem cells that are significantly HLA mismatched.

"The primary limitations for successful allogeneic stem cell transplantation in older patients relates to life-threatening toxicities of fully ablative conditioning regimens with associated comorbid conditions as well as GVHD, which is more frequent, more severe, and less well tolerated in these tenuous patients," he said. "Reduced-intensity conditioning regimens combined with UCB as a source of allogeneic stem cells can potentially bypass many of these hurdles."