Your SlideShare is downloading. ×
  • Like
Alterative Donor HSCT
Upcoming SlideShare
Loading in...5

Thanks for flagging this SlideShare!

Oops! An error has occurred.


Now you can save presentations on your phone or tablet

Available for both IPhone and Android

Text the download link to your phone

Standard text messaging rates apply


Published in Health & Medicine , Education
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
    Be the first to like this
No Downloads


Total Views
On SlideShare
From Embeds
Number of Embeds



Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

    No notes for slide


  • 1. Alterative Donor HSCT Now Everyone Has a Donor Richard Champlin, M.D.
  • 2. Donor Priority • HLA matched sibling • HLA matched unrelated donor • Alternative Donor –One antigen mismatched related or unrelated donor –Cord Blood –Haploidentical Donor
  • 3. Best Available Donor
  • 4. Busulfan-Fludarabine AlloSCT for AML
  • 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
  • 10. CumulativeIncidence SIB P < 0.01 MMUD MUD DUCB 0.0 0.2 0.4 0.6 0.8 1.0 0 1 2 3 4 5 Years post-transplantation Minnesota-Fred Hutchinson Experience-Relapse by Donor Type Brunstein et al 2010
  • 11. N=3038 Bone marrow Peripheral blood Transplants Year 1980 - 2003 N=280 Cord blood transplants Year 1996 - 2010 59% 25% M. D. Anderson BMT Department Minority Allo-transplants by Stem Cell Source
  • 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
  • 14. Post Transplant Cyclophosphamide for Haploidentical Transplantation Luznik,L. Fuchs E.J. et al
  • 15. Ciurea BBMT 2012
  • 16. Figure 2 Ciurea 2012
  • 17. 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
  • 18. Cumulative incidence of nonrelapse mortality (NRM) and relapse of malignancy by donor type: (A) NRM and (B) relapse; both were analyzed as competing risks. Bashey A et al. JCO 2013;31:1310-1316 ©2013 by American Society of Clinical Oncology
  • 19. Adjusted estimated probabilities of (A) overall and (B) disease-free survival by donor type. Bashey A et al. JCO 2013;31:1310-1316 ©2013 by American Society of Clinical Oncology
  • 20. 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