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Haematological Malignancies
proved to be superior to conventional chemotherapy in the pre-imatinib adult patients.
17
Initial experiences with unrelated cord blood stem cell
era for patients with Philadelphia-chromosome-positive (Phi
+
) ALL transplant (UCB-SCT) showed the importance of receptor age, the cell
lacking a matched related donor.
25
The phase of the disease at transplant dose infused and the degree of HLA disparity in transplant outcome.
40
is one of the most important factors influencing relapse in the unrelated Cord blood progenitors are more permissive with HLA disparities, and it
transplant setting for both USCT and unrelated cord blood SCT.
12,13,22,30,31
is standard practice to allow zero to two HLA mismatches using low-
Advanced disease status is associated not only with a higher relapse resolution typing methods for HLA-A and -B and high-resolution
rate but also with a higher TRM.
12–14
The follow-up of 609 adult patients molecular typing for HLA-DRB1. In contrast, recommendation for
after relapse of ALL in the UKALL12/ECOG 2993 study revealed that only unrelated bone marrow or PBSC transplants is more restrictive and
a very highly selected subgroup of patients were able to receive SCT considers zero to one mismatch using high-resolution molecular typing
after relapse, resulting in a superior overall survival (OS) (16% for of eight or 10 allelles (HLA-A, -B, -C, -DRB1, -DP). The use of high-
matched unrelated and 23% for sibling allograft SCT) than those resolution HLA typing by sequencing for HLA-A, -B, -C and -DQ has
receiving chemotherapy alone (4%).
32
The grim prognosis of adult shown that the degree of mismatching in UCB-SCT is even higher than
patients with high-risk ALL after relapse justifies considering alternative expected. However, it does not seem to have a significant impact on the
donor transplants in first CR if a sibling donor is lacking. The prevention long-term clinical outcome in the UCB-SCT setting.
41
of relapse remains the most important goal for long-term survival in ALL
patients. Moreover, the detection of residual disease during the post- Comparison of Outcome Between Unrelated Donor
transplant period may be useful to diagnose recurrent disease early, Transplant and Unrelated Cord Blood Transplant
allowing early therapeutic interventions.
33
Many studies have described the outcome of UCB-SCT and compared
the results with those from UD-SCT. In most studies comparing the two
Stem Cell Source sources, the proportion of patients with more advanced disease or
Unrelated Donor Stem Cell Transplant with poor-prognosis leukaemia was higher in the UCB-SCT group.
For many years, bone marrow has been the stem cell source of choice Moreover, some studies included both AML and ALL or a variable
for unrelated transplants. However, the mobilised peripheral blood stem proportion of paediatric patients. Finally, the OS, DFS and TRM were
cell (PBSC) has been widely adopted by many centres as the preferred estimated at different periods of time (one to five years or more) and
unrelated stem cell source. Some data have pointed out a worse a short period follow-up underestimated late TRM (see Table 1). Most
prognosis for patients receiving PBSC versus bone marrow graft in the comparative studies of UCB-SCT versus bone marrow SCT for
unrelated setting for ALL
34,35
due to a higher incidence of chronic graft- leukaemia from UDs have shown similar outcomes.
18–20
Initial
versus-host disease (GvHD) in former patients. Some groups have comparisons between UCB-SCT and UD-SCT (including only bone
explored T-cell depletion of unrelated PBSC
36
or bone marrow
12
without marrow SCT) showed that patients receiving an UCB-SCT had a
showing a clear advantage in survival for T-cell-depleted grafts. delayed neutrophil and platelet engraftment and a lower incidence of
Cornelissen et al.
12
reported their experience with unrelated bone acute GvHD, in spite of a greater HLA mismatch between the patient
marrow transplant provided by the National Marrow Donor Program and the graft.
18,19
However, the survival rate was similar when a
(NMDP) collection centres for transplant in adult patients with ALL, and comparison of procedures was performed at an early stage for
concluded that the main factors for a better DFS were first CR at SCT, transplants with cord blood progenitors in adult patients. Three major
absence of HLA-A, -B or DRB1 mismatch, negative cytomegalovirus studies have compared the outcome of paediatric patients with ALL
(CMV) serology and a shorter interval from diagnosis to transplantation. after USCT, focusing on the haematopoietic stem cell source.
42–44
In
For patients in first CR, the OS (95% confidence interval [CI]), relapse rate paediatric patients, a better outcome for patients receiving a fully
and TRM at two years were 40% (13%), 6% (7%) and 54% (13%), matched UD bone marrow transplant has been reported, and this was
respectively. These data included patients from an early period confirmed by some groups in an adult population.
19
In terms of adult
(1988–1999), but more recent reports incorporating high-resolution patients, Atsuta et al.
45
carried out a large study using the Japanese
typing HLA methods for HLA-A, -B and -C have shown better expected registries to explore the impact of stem cell source (bone marrow or
survival in the USCT setting with a decreased TRM.
14,37
A large experience umbilical cord) for adult patients with acute leukaemia, making a
with 169 adult patients with Philadelphia-chromosome-negative (Phi
-
) disease-specific comparison. In the ALL group, there were no
ALL in first CR reported a 38% DFS probability, with a 20% TRM and a 42% differences in terms of TRM, OS or DFS when eight out of eight
relapse rate at five years. The most important factors determining poor matched bone marrow or UCB were compared. There was a trend
survival besides the degree of HLA mismatch and T-cell depletion were towards a higher cumulative incidence of relapse in UCB recipients. As
a white blood cell count >100x10
9
/l, more than eight weeks to attain CR expected, UCB-SCT was associated with a lower incidence of chronic
and CMV seropositivity. The analysis of 1,874 unrelated bone marrow (especially extensive) and acute GvHD. The recurrence of the primary
transplantations under the auspices of the NMDP showed that low- disease was the leading cause of death for high-risk ALL patients.
resolution mismatches have a more severe impact on survival than Other studies did not find differences in relapse rate when UCB-SCT
mismatches detectable only with high-resolution typing techniques.
38
and UD-SCT were compared.
18–20,45
Moreover, the impact of a mismatch at a particular locus depended on
the total number of mismatches between donor and recipient
39
with the The disadvantages of using UCB as a haematopoietic source are the
T-cell undepleted grafts. The adverse impact of mismatch on unrelated limited number of stem cells in the unit, the impossibility of performing
donor stem cell transplant (UD-SCT) outcome was especially marked in cellular therapy with lymphocytes belonging to the donor, the delayed
patients without advanced malignancy. haematological recovery and the delayed immune reconstitution.
However, a higher infectious vulnerability may be compensated by a
Unrelated Cord Blood Stem Cell Transplant lower risk of GvHD.
18,46
Due to slower haematopoietic and immune
Unrelated cord blood was initially introduced as an alternative source for reconstitutions after UCB-SCT, severe infections are more frequent after
SCT for paediatric patients, but more recently it has been considered for UCB-SCT than after non-T-cell-depleted progenitors in UD-SCT,
46 EUROPEAN HAEMATOLOGY
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