SAN FRANCISCOUmbilical cord blood from unrelated donors can
be a useful source of hematopoietic stem cells for treating hematologic
malignancies in adults as well as infants, according to a multicenter study
presented by Mary J. Laughlin, MD, at the 42nd Annual Meeting of the
American Society of Hematology (ASH). Dr. Laughlin is director of the
Allogeneic Transplant Program, Case Western Reserve University, University
Hospitals Ireland Cancer Center.
Cord blood has been used sporadically since 1988 for
transplantation in children with leukemias and other blood disorders. The
treatment is new in adult patients, however. The challenge with adults, Dr.
Laughlin said, is their greater size and low graft cell dose received.
In the new study, 68 adult patients under the age of 55 were
transplanted using HLA-mismatched unrelated donor umbilical cord blood (UCB);
54 had hematologic malignancies. Preferred UCB units were those matched at a
minimum of 3 of 6 HLA loci and containing a minimum of 1 × 107/kg
nucleated cells; 71% of patients received grafts disparate at 2 or more HLA
There were 8 early deaths due to infection and/or toxicity. Of
60 patients surviving more than 28 days after UCB transplantation, 55 (90%)
achieved neutrophil engraftment. The researchers were able to achieve a faster
rate of neutrophil recovery with a higher dose of transplanted cells.
There were 5 primary graft failures in patients who survived
for more than 28 days, but so far there have been no late graft failures, Dr.
Laughlin said. Probability of graft-vs-host disease (GVHD) was .60 for grade
2-4 acute GVHD, .20 for grade 3-4 acute GVHD, and .38 for chronic GVHD. Chronic
GVHD was limited stage in all but one patient.
Eighteen patients remain alive with no evidence of disease for
at least 48 months after transplant, for a probability of disease-free survival
of .26. Four patients relapsed at 3, 6, 10, and 11 months after transplant, for
a probability of relapse of .14.
The researchers thus concluded that UCB from unrelated donors
can successfully engraft adult recipients with high-risk or recurrent
hematologic malignancies and marrow failure syndromes. "I must
emphasize," Dr. Laughlin said, "that these are phase I studies with
patients who are at very high risk, multiply relapsed, etc."
Cord Blood Advantages
One of the advantages of using cord blood instead of bone
marrow for transplant is that it takes far less time to find a suitable donor.
"This is a tremendous advantage, particularly for patients with acute
leukemias," Dr. Laughlin said. "For the vast majority of our
patients, we are able to identify and mobilize a suitable unrelated graft
within 3 weeks."
Despite disparities in HLA antigens between donor and
recipient, the study found that unrelated UCB transplant is associated with a
relatively low incidence of severe acute or chronic GVHD.
Because of the unique properties of umbilical cord blood, a
less than perfect match is acceptable for the transplant to be successful, Dr.
Laughlin said. This increased tolerance may be related to the unique immunology
of pregnancy, which tolerates immune differences between two individuals
(mother and baby) who are not genetically identical.
Umbilical cord blood transplantation may also be a better
alternative to marrow transplantation because the cord blood can be collected
at no risk to the donor, she added.