Laughlin_edit.qxp 29/5/07 4:30 pm Page 30
Fetal & Maternal Healthcare
Figure 1: Cumulative Incidence of Neutrophil Recovery After Bone
higher minimum dose > 2 x 10
7
/kg. The majority of adult UCB recipients
Marrow and Cord-blood Transplantation
have received grafts mismatched at two or more HLA loci. Importantly, adult
recipients have generally been high-risk patients appropriate for phase I
100
studies and their poor survival may not be fully attributable to the UCB graft
Bone marrow, matched
Cord blood, mismatched infused.
26
Multi-institutional, prospective phase II studies are awaited.
Bone marrow, mismatched
80
Two recent large European
12
and North American
11
retrospective studies
outlining transplants of UCB or bone marrow from unrelated donors in
60 adults with acute leukemia have been reported. Investigators in the Acute
Leukemia Working Party of European Blood and Marrow Transplant Group:
%
EUROCORD-NETCORD Registry compared outcomes in 682 adults with
40
acute leukemia who received HSC transplant from unrelated donors: 98
patients received UCB and 584 received bone marrow. The transplants were
performed from 1998 through 2002. Recipients of cord blood were
20
younger than recipients of bone marrow (median 24.5 versus 32 years of
age; p<0.001), weighed less (median 58 versus 68 kg; p<0.001), and had
0 12345
Years
Recently, fludarabine has
367 138 120 99 60 42
been introduced to provide
.
at risk 83 23 16 14 8 5
No immunosuppression and avoid
150 38 28 24 12 5
use of antithymocyte globulin in
Despite early differences, the cumulative incidence of neutrophil recovery at day 100 was similar after the the non-ablative setting.
transplantation of mismatched bone marrow and of cord blood. The corresponding cumulative incidence
after transplantation of HLA-matched bone marrow was significantly higher.
11
more advanced disease at the time of transplantation (52% versus 33%,
Figure 2: Adjusted Probability of Leukemia-free and Overall
Survival After Bone Marrow and Cord-blood Transplantation
p<0.001). All marrow transplants were HLA-matched, whereas 94% of
cord-blood grafts were HLA-mismatched (p<0.001). The median number of
100 nucleated cells that were infused was 0.23 x 10
8
/kg recipient’s body weight
Bone marrow, matched
for cord blood and 2.9 x 10
8
/kg for bone marrow (p<0.001). Multivariate
Cord blood, mismatched
analysis showed lower risks of grade II–IV acute GVHD after cord-blood
Bone marrow, mismatched
80
transplantation—relative risk 0.57; 95% confidence interval (CI), 0.37–0.87;
p=0.01—but neutrophil recovery was significantly delayed—relative risk
0.49; 95% CI, 0.41–0.58; p<0.001. The incidence of chronic GVHD,
60
transplantation-related mortality, relapse rate, and leukemia-free survival
%
were not significantly different in the two groups. These investigators
concluded that cord blood from an unrelated donor is an acceptable
40
alternative source of hematopoietic stem cells for adults with acute
leukemia who lack an HLA-matched bone marrow donor.
12
20
Investigators in the International Bone Marrow Transplant Registry (IBMTR)
in North America compared the outcomes of the transplantation of
hematopoietic stem cells from unrelated donors in adults with leukemia
0 12345
who had received cord blood that was mismatched for one HLA antigen (34
Years
patients) or two antigens (116 patients), bone marrow that had one HLA
367 138 120 99 60 42
mismatch (83 patients), and HLA-matched bone marrow (367 patients).
11
.
at risk 83 23 16 14 8 5
Cox proportional-hazards models were used to analyze the data. Similar to
No
the European patients, cord-blood recipients were younger and more likely
150 38 28 24 12 5 to have advanced leukemia than were bone marrow recipients, and they
received lower doses of nucleated cells. Hematopoietic recovery was slower
The adjusted probability of three-year survival without a recurrence of leukemia was 19% for recipients of
with transplantation of mismatched bone marrow and cord blood than with
mismatched marrow, 23% for recipients of cord blood, and 33% for recipients of HLA-matched marrow.
matched marrow transplantations (see Figure 1). Acute GVHD was more
Probabilities were adjusted for age, disease status at transplantation, and positivity for cytomegalovirus in the
donor, recipient, or both.
11 likely to occur after mismatched marrow transplantation, and chronic GVHD
was more likely to occur after cord-blood transplantation. The rates of
30 US OBSTETRICS AND GYNECOLOGY 2007
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75