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C H A P T E R 107

UNRELATED DONOR CORD BLOOD TRANSPLANTATION FOR

HEMATOLOGIC MALIGNANCIES

Rohtesh S. Mehta, Amanda Olson, Doris M. Ponce, and Elizabeth J. Shpall

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Cord blood (CB) is now routinely used as an alternative stem cell CD34 cell dose was superior to infused TNC dose in determining
source for patients without a matched related or unrelated peripheral the success of neutrophil and platelet engraftment in an analysis of
blood (PB) or bone marrow (BM) graft. In the late 1980s, Broxmeyer 102 CBT (median age, 7.4 years) with recipients of units with less
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and colleagues reported that CB is a rich source of hematopoietic than 1.7 × 10 CD34 cells/kg having a significantly lower neutrophil
stem cells (HSCs) and progenitors, setting the stage for the first engraftment incidence of 72% at a median of 34 days compared with
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related donor CB transplantation (CBT) in 1988. Subsequently, higher cell doses (p < .01).
placental blood banking programs were initiated in 1992 to 1993 in These analyses have the limitation that cell dose and HLA match
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New York, Milan, Dusseldorf, and Paris. The first unrelated donor are analyzed separately and yet these graft characteristics must be
CBT was performed in 1993, and the first unrelated donor CBT considered together in the selection of individual units. In 2009,
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series were published in 1996. Public CB banks have since grown Rocha and Gluckman reported on 925 recipients of single-unit
in number with an estimated 600,000 public CB units banked glob- CBT transplanted for malignant disease and found that neutrophil
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ally. Furthermore, the number of CBT continues to increase. In engraftment was related to the number of cells infused (p < .0001)
2010–2011, CBT accounted for more than one-fourth of all alloge- and HLA match with a significant difference between zero and one
neic stem cell transplants (SCT) in patients younger than 20 years, (81%), two (75%), and three and four (63%) HLA disparities (p =
but less than 10% among patients older than 20 years. 8 .037). The role of HLA match was partially abrogated by an increase
The use of CB stem cells has several unique benefits. Given it is in cell dose except for recipients of highly mismatched grafts. In
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a cryopreserved product, it has rapid accessibility, does not carry the 2010, Barker et al analyzed the combined effect of TNC dose and
risk of donor unavailability, minimizes the risk of infection transmis- donor–recipient HLA match in 1061 single-unit CBT recipients
sion, has less stringent human leukocyte antigen (HLA) match transplanted for hematologic malignancies after myeloablative con-
requirements because of the naive neonatal immune system, and is ditioning. The best neutrophil engraftment was associated with a
associated with lower than expected rates of graft-versus-host disease fully HLA-A, HLA-B antigen, and HLA-DRB1 matched unit or a
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(GVHD). Barker et al reported that recipients of CB grafts were cryopreserved TNC greater than 10.0 × 10 /kg with one or two
transplanted a median of 25 days earlier than unrelated donor mismatches. The worst was with a unit with three mismatches or a
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transplant recipients. This is particularly advantageous for patients in cryopreserved TNC below 2.5 × 10 /kg with one or two mismatches
need of an urgent transplant. Further, CB has facilitated the extension (Fig. 107.2). There was no difference in neutrophil engraftment in
of transplant access especially to racial and ethnic minorities. Although recipients of one versus two mismatched units, and in this setting,
there are more than 11 million potential marrow donors in the the TNC dose determined neutrophil engraftment.
National Marrow Donor Program (NMDP) registry, only 27% are
from racial and ethnic minority groups compared with CB units
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where 45% belong to the minority group. A recent NMDP registry Graft-Versus-Host Disease
analysis showed that the likelihood of finding an optimal (8/8 or 7/8
HLA-matched) adult donor is 75% for whites of European decent, Single-unit CBT is associated with a lower than expected incidence
but it is less than 20% for American blacks and varies from 27% to of GVHD for the degree of donor–recipient HLA mismatch, which
52% for other ethnicities. By contrast, a suitable CB graft can be allows use of units with a less stringent HLA match (i.e., only a 4-6/6
obtained for 80% to 96% of adult patients across all races and almost HLA-A, HLA-B antigen, HLA-DRB1 allele match). Incidences of
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universally for younger patients. (Fig. 107.1) grade II–IV acute GVHD have been reported between 10% and 50%
and likely vary according to the GVHD prophylaxis used and the
inclusion of antithymocyte or antilymphocyte globulin (ATG/ALG)
SINGLE UNIT CORD BLOOD TRANSPLANTATION in the conditioning. 12,15,22–26 As with transplantation of adult donors,
the major graft determinant of acute GVHD is the HLA match,
Engraftment although with CB, the permissible mismatch is considerably greater
than can be tolerated with HSC transplantation from adult donors.
Unrelated donor CBT was initiated using single-unit grafts. Studies Although an effect of HLA mismatch could not be demonstrated
have demonstrated that higher cell dose and better donor–recipient in early series of unrelated donor CBT, 14,15,18,19 a later large NYBC
HLA match are independent factors associated with improved neu- retrospective analysis of 1061 single-unit CBT recipients demon-
trophil engraftment. 12–19 The 1997 Eurocord analysis was the first strated that recipients of matched CB units had significantly less
large series reporting on 143 related and unrelated donor CBT grade III–IV acute GVHD and that increasing mismatch was associ-
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recipients. In unrelated donor CBT recipients, improved neutrophil ated with a progressively increased risk of severe acute GVHD.
and platelet engraftment were both associated with a higher total There was also an association between the degree of mismatch and
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nucleated cell (TNC) dose above the median of 3.7 × 10 /kg and chronic GVHD, although this only reached significance in recipients
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donor–recipient HLA match. In 1998, Rubinstein et al confirmed of units with three mismatches. 12
these findings in an analysis of 562 CBT facilitated by the New York The influence of deeper HLA-matching using allele-level high reso-
Blood Center (NYBC) as did an updated analysis by Gluckman and lution typing as well as the impact of HLA-C matching have
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Rocha in 2004. In 2002, Wagner et al reported that infused also been explored in single-unit CBTs. In the Cord Blood
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