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Chapter 107 Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies 1639

CORD BLOOD UNIT SELECTION double-unit graft selection, a minimum threshold for each unit of a
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double-unit graft is needed. Based on the analysis by Avery et al a
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Efficient search and selection of CB units requires decision making minimum TNC dose threshold of at least 2.0 × 10 /kg is currently
as to what banks to consider and what factors to prioritize in unit recommended in DCBT. The age of cryopreserved CB units should
selection. The unit selection algorithm currently used at the Memo- not be criteria when selecting CB units. A study showed that units
rial Sloan-Kettering Cancer Center (MSKCC) is shown in Fig. cryopreserved for up to 11 years before transplantation had no
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107.5. The M.D. Anderson Cancer Center (MDACC) uses a impact on postthaw TNC recovery or neutrophil or platelet engraft-
similar approach. Primary unit selection criteria are based on the ment in 288 single CBT recipients. 64
prethaw cryopreserved TNC/kg, the unit-recipient HLA match Recent analyses have highlighted new factors to be considered in
(4-6/6 of HLA-A, HLA-B antigen, and HLA-DRB1 allele), and the unit selection. The 2009 NYBC analysis evaluated the impact of fetal
bank of origin based on the authors’ experience with the bank and exposure to noninherited maternal antigens (NIMAs) on the outcome
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their accreditation. Other factors such as the availability of confirma- of CBT. The 79 single-unit CBT recipients that had an HLA-
tory HLA typing on an attached segment and the completeness of mismatched antigen that was identical to a donor NIMA engrafted
maternal infectious disease marker and hemoglobinopathy testing are earlier and had lower TRM and overall mortality. There was also a
also taken into account. lower tendency toward relapse among patients with myeloid malig-
The exact threshold for acceptable TNC/kg has yet to be estab- nancies. Subsequently, in 2011, the NYBC analyzed the effect of
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lished and varies with HLA match. For example, the 2010 NYBC HLA-mismatch vector in 1202 single-unit CBT recipients. They
analysis of single-unit CBT demonstrated that recipients of units identified 98 donor–recipient pairs with only unidirectional mis-
with a 6/6 HLA match had the best transplantation outcomes matches (58 in the graft-versus-host direction and 40 in the rejection
regardless of the cryopreserved TNC dose. By contrast, recipients of direction). The graft-versus-host vector group had faster engraftment
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4/6 units required a TNC dose of 5.0 × 10 /kg or greater to achieve and decreased TRM and overall mortality compared with the one-
similar TRM and DFS to that of recipients of 5/6 units with TNC bidirectional mismatch reference group, but recipients of rejection
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of 2.5–4.9 × 10 /kg. Although the numbers of DCBT recipients only mismatched units had slower engraftment, a higher incidence
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available do not yet permit such analysis, it is likely that similar of graft failure, and higher relapse rates. Also in 2011, Eapen et al
principles will be found associated with the engrafting unit in reported that HLA-C matching is important in addition to HLA-A,
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DBCT recipients. Indeed, Avery et al have reported that a higher HLA-B, and HLA-DRB1, although how to balance this against TNC
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infused TNC and CD34 cell dose in the engrafting unit of a dose needs to be further investigated. Finally, the potential impor-
double-unit pair was strongly associated with the speed and success tance of antigens in the patients that are shared with inherited
of neutrophil engraftment. However, because it is not currently paternal antigens in the CB donor that could be a target for maternal
possible to predict which unit will predominate at the time of T cells has recently been reported as a potential mechanism of reduced
relapse after CBT. 67
The findings concerning the importance of HLA-mismatch vector
and HLA-C can be immediately incorporated into CB unit selection
Evaluate search reports for units 4−6/6. algorithms, but incorporation of NIMA and inherited paternal
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HLA matched with TNC ≥2.0 × 10 /kg antigen will require banks to provide maternal typing. In addition,
although the best available CB unit or units are selected as the graft,
it is important to identify and reserve at least one backup unit in the
Review information and bank of origin for each unit. event of problems with unit shipment, mislabeling, problems with
Obtain missing unit information. thaw, or graft failure. 68–70 At both MSKCC and MDACC, the authors
Request CT of units of interest. select one domestic unit as backup to ensure the timely infusion of
Prepare CB search summary report. an optimal CB product.
It is unclear if recipients should be assessed pretransplant for
Review CTs: update
search summary. anti-HLA antibodies possessing specific alloreactivity against CB
units (donor specific antibodies, DSAs), as these may have an impact
Rank units according to HLA-A, HLA-B on post-DCBT outcomes although the data are rather conflicting.
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antigen, HLA-DRB1 allele match. List highest Cutler et al analyzed the outcomes of 73 DCBT recipients after
to lowest TNC within each match grade either myeloablative or RIC regimens. DSAs were detected in 24%
(correct for RBC if needed). of the patients, of which about 60% were directed against one CB
unit and the rest targeted both units. Rate of graft failure was drasti-
1st choice 2nd choice 3rd choice
cally higher in patients with DSAs directed against both units (57%)
compared with those with DSAs against single unit (18%) or those
6/6 units: 5/6 units: 4/6 units: with no DSAs (5.5%). Also, time to neutrophil engraftment was
Choose Choose Choose prolonged (29 days versus 21 days; p = .004) and day 100 mortality
largest TNC. largest TNC. largest TNC. or relapse was increased in patients with any DSA. Noteworthy, more
than 70% of patients received RIC regimens that included ATG.
Another study using RIC regimens in 294 CBT recipients found
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DSAs in 14 patients (4.7%), half of whom received single CBT. As
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seen in the Cutler study, patients with DSAs had significantly worse
Make final selection of unit(s) of graft neutrophil engraftment (44% versus 81%, p = .006), 1-year TRM
(units 1a and 1b if double unit graft). (46% versus 32% p = .06) and a trend towards poor OS (42% versus
Prepare domestic backup unit(s). 29%; p = .07) compared with those without DSAs. On the contrary,
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Brunstein et al found no impact of DSAs in their study of 126
Plan shipment(s). DCBT recipients. Overall, DSAs were present in about 15% of the
patients, of which two-thirds were directed against one CB unit and
Fig. 107.5 CURRENT MEMORIAL SLOAN-KETTERING CANCER one-third against both units. The cumulative incidence of neutrophil
CENTER AND M.D. ANDERSON CANCER CENTER SCHEMA OF engraftment was similar in patients with DSAs against at least one
HOW TO SELECT CORD BLOOD (CB) UNITS. CT, Confirmatory CB unit (78%; median, 24.5 days) compared with patients with
typing; HLA, human leukocyte antigen; RBC, red blood cell; TNC, total irrelevant anti-HLA antibodies (84%; median, 24 days) and those
nucleated cell. (From Barker JN, Byam C, Scaradavou A: How I treat: the selection with no antibody (86%; median, 19 days), p = .54. Overall, 35% of
and acquisition of unrelated cord blood grafts. Blood 117:2332, 2011.) entire study cohort received myeloablative conditioning, but the type