5. Survival of patients with early, intermediate, and advanced disease depending on degree of
HLA matching (8/8, 7/8, and 6/8) for HLA-A, -B, -C, and -DRB1.
Lee S J et al. Blood 2007;110:4576-4583
6. Pros and Cons
• Matched unrelated donor-
– Pros:
• Results ~= matched sib (GVHD higher)
• Large system of registries, can find high res 8 of 8 match for >
50%
• Can go back to donor for DLI, second transplant, cell therapy
– Cons:
• Time search to transplant 2-4 months, too long for urgent patients
• 8 of 8 match in only about half, lower if minority race/ethnic origin
• Donor unavailability (at least 35%)
• Need to carefully coordinate collection and transplant, locked in to
dates,
• Uncertain donor availability for second transplants, DLI
• Hard to coordinate with chemo for patients with relapsed disease
7. Pros and Cons
• One Antigen Mismatched Unrelated Donor-
– Pros:
• Available donor for >90%
– Cons:
• All the limitations of matched unrelated donors
• Higher risk of rejection, GVHD, infections, TRM
• Higher cost/resource requirements- corresponds to
complications
• Survival about 10% less than matched transplant
8. Pros and Cons
• Cord Blood
– Pros:
• Immunologically immature- less prone to produce GVHD
• Less risk of transmitting infection
• Immunologically naïve- no preexisting immunity
• Can successfully transplant across HLA mismatch
• Can identify 5 of 6 or 4 of 6 match for most patients
• Has potent GVL effect, ?better than BM
• Cells already collected, shorter time search to transplant
• Results improving,
– in recent reports = matched unrelated
9. Pros and Cons
• Cord Blood
– Cons:
• Low cell dose, slow recovery hematopoiesis and
immunity,
• Survival depends on cell dose- double cord required for
most adults
• GVHD major problem (with 4 of 6 or 5 of 6 matched Tx)
• Relatively high TRM
• Can’t go back to the donor for more cells or DLI (?CLI)
• Resource intensive
– $$$ for cord(s)
– $$$$ for transplant care
– Staff/facility requirements
– $$$$$ Need system of banks, cost for collection, QA, storage
12. Pros and Cons
• Haploidentical related
– Pros:
• Almost everyone has a haplo match (parent,
child, half of siblings)
• Improved results with post transplant
cyclophosphamide, recent results = MUD
• Donor immediately available to transplant
center, allows close coordination with
chemotherapy
• Don’t need a registry/ banks
• Costs similar to matched sibling transplant
13. Pros and Cons
• Haploidentical related
– Cons
• Ultimate challenge- most alloreactive transplant
• Historically, high rate rejection/GVHD/TRM
• T-cell depletion- slow immune recovery,
variable results, poorer results in adults
• Studies with post transplant cyclophosphamide-
improved results, but short follow up
• Concerns that measures to reduce GVHD will
also reduce GVL and increase risk of relapse
18. Cumulative incidence of graft-versus-host disease (GVHD) by donor type: (A) grades 2 to 4
acute GVHD, (B) grades 3 to 4 acute GVHD, (C) clinically extensive chronic GVHD, and (D)
severe chronic GVHD by National Institutes of Health consensus criteria.
Bashey A et al. JCO 2013;31:1310-1316
26. Conclusions
• HLA matched sibling- still donor of choice
• Many centers question whether MUD is next
priority, can move more quickly to cord blood or
haplo transplant
• Improving results with Cord Blood and
Haploidentical transplants rivaling matched sib and
MUD
• Do cord blood transplants mediate greater GVL
effect?
• Are haplo transplants with post Tx Cy associated
with more relapse?
• Almost every patient in need has a donor for HSCT
