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Transfusion Post Allogeneic Stem Cell Transplant

Transfusion Post Allogeneic Stem Cell Transplant. Robert C. Skeate, MD MS. Overview. Discuss stem cell sources for transplant -Advantages and disadvantages -Double cord blood transplants and why they are done That ABO type is not often a consideration Consequences of ABO mismatch

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Transfusion Post Allogeneic Stem Cell Transplant

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  1. Transfusion Post Allogeneic Stem Cell Transplant Robert C. Skeate, MD MS

  2. Overview • Discuss stem cell sources for transplant-Advantages and disadvantages-Double cord blood transplants and why they are done • That ABO type is not often a consideration • Consequences of ABO mismatch • Natural history of ABO type post transplant • Choosing blood products post transplant • Investigation of increasing O neg blood use at the medical center where I previously worked

  3. Options for Stem Cell Transplant • Obtain stem cells directly from bone marrow • Obtained via invasive procedure in the operating room • Are able to collect all the cells you need

  4. Options for Stem Cell Transplant • Peripheral blood stem cells • Very often can obtain needed cell dose

  5. Options for Stem Cell Transplant • Cord Blood • Limiting factor is small cell dose

  6. Choosing a Stem Cell Product • Most important parameter: HLA match-Prefer a matched sibling donor (30%)-Want a “6 out of 6” match-HLA-A, HLA-B, and HLA-DR genes-Typically use PBSC, but can do marrow if unable to get enough cells via apheresis • No matched sibling?-Unrelated HLA matched donor (30%)-Not enough donors (HLA type and race)-Many month delay before transplant Majhail, N, Brunstein, C, & Wagner, J. Double umbilical cord blood transplantation. Current Opinion in Immunology 2006; 18:571–575

  7. Choosing a Stem Cell Product • HLA-matched unrelated cord blood • Cell dose needed = (TNC) 2.5 X 107/ Kg • Only 25% of adults are small enough given typical cell doses in cord blood units • Can increase the dose by using two cord blood units (double cord blood transplant) • Sustained hematopoiesis after DUCBT is usually from one donor • Increasingly common at U of MN Majhail, N, Brunstein, C, & Wagner, J. Double umbilical cord blood transplantation. Current Opinion in Immunology 2006; 18:571–575

  8. Advantages of Cord Blood • Ease of procurement • Absence of risk for donors • Decrease likelihood of infections (CMV) • Store HLA-typed units frozen for rapid use Cord compared to unrelated matched PBSC • Decreased graft-vs-host disease • Similar long term survival • Less well HLA-matched have similar outcome Gluckman, E. History of cord blood transplantation. Bone Marrow Transplantation 2009; 44:621–626

  9. Bensinger, W, and Storb, R. Allogeneic peripheral blood stem cell transplant. Rev Clin Exp Hematol 2001; 5(2):67-86

  10. Haspel, R & Ballen, K. Double cord blood transplants: filling a niche? Stem Cell Rev 2006; 2(2):81-6

  11. Brunstein, C & Laughlin, MJ. Extending cord blood transplant to adults: dealing with problems and results overall. Semin Hematol 2010; 47(1):86-96

  12. What Parameter Not Considered? • Donor and recipient ABO type • Recipients become donor ABO type over time so one would think this would have an impact • 25% or so are mismatched for ABO • ABO mismatch does not impact:-Overall graft failure-Graft vs. host disease-Survival Yazer, M. & Triulzi, D Immune hemolysis following ABO mismatched stem cell or solid organ transplantation. Current Opinion in Hematology 2007, 14:664–670

  13. Consequences to ABO Mismatch • There is a downside to ABO mismatch • Antibodies stay around for many weeks post-transplant • Destroy red cells and precursors 1. Delayed red cell engraftment • Increased RBC transfusion requirements • Pure red cell aplasia • Post-transplant hemolysis

  14. Consequences to ABO Mismatch • Delayed RBC engraftment:41 days for mismatched20 days for matched • Pure red cell aplasia (Not graft failure?) • Recipients engrafts with white cells and platelets but has no red cell production • ABO antibodies destroy red cell precursors • Frequency 8 - 38% of mismatched Yazer, M. & Triulzi, D Immune hemolysis following ABO mismatched stem cell or solid organ transplantation. Current Opinion in Hematology 2007, 14:664–670

  15. Post-Transplant Hemolysis Example: Recipient A Donor B • Acute hemolysis of the B red cells in the stem cell product by the recipient’s anti-B • Subacute hemolysis of recipient’s A red cells due to anti-A from infused donor lymphocytes (passenger lymphocyte syndrome) • Delayed hemolysis of recipient-type A red cells as the donor immune system engrafts • Do not want to potentiate this by transfusing mismatched red cells

  16. Post-Transplant Hemolysis Petz, L. Immune hemolysis associated with transplantation. Seminars in Hematology 2005; 42:145-155

  17. ABO Type Post-Transplant Over weeks to months, recipient develops donor hematopoiesis and immune function • Recipient red cell type at first • Slowly transitions to donor type • Will have mixed field in the transition • Recipient back type at first (anti-A and/or B) • Is often weak due to chemotherapy • Slow transition to donor back type • Often is weak, incomplete, or not present • Transfused products can obscure transition

  18. Isoagglutinins and RBC Engraftment • Comparison of RBC engraftment to determine if preparative regimen matters • Myeloablative (SCT) PBSC transplant • Non-myeloablative (NST) PBSC transplant • January 1997 - May 2000 at NIH • Groups were concurrent, consecutive patients with HLA matched family members • Major ABO mismatch patients • 16 NST and 12 SCT (90 day survivors) Bolan, C. et al. Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation. Blood. 2001; 98:1687-1694

  19. Time to Donor RBC “Chimerism” Chimerism = Detect donorRBCs on two consecutiveperipheral blood samples(2 - 5 % donor cells)

  20. Time to absence of Isohemagglutinin

  21. RBC Chimerism and Isohemagglutinin NST Patients

  22. Red Cell Transfusion Strategy Yazer, M., Triulzi, D. Immune hemolysis following ABO-mismatched stem cell or solid organ transplantation. Curr Opin Hematol 2007; 14:664–670

  23. 1993-1997 292 BMTs Before Remove Plasma n = 153 Matched Mismatched n = 139 120 BMTs After Remove Plasma Benjamin, R, & Antin, J.Transfusion 1999; 39: 1273-4

  24. Protocol to Switch to Donor-type Blood Criteria to switch to donor-type blood: 1. Only donor-type red cells present 2. Back-type does not have to match donor to give donor cells* 3. No transfusions for 120 days 4. 100% donor type by molecular studies *Cells must be compatible with back-type

  25. Monthly Percent O- Use UMMC (1/03 – 4/07)

  26. Who Was Using O- RBCs? • We performed a retrospective review of all O- transfusions over a 2 month period • Noted in particular instances where O- cells given to non-O- patients

  27. O- for Non-O- Patients

  28. Which Transplants Used O-Neg? • Retrospective review of all allogeneic stem cell transplants over a 5 month period • Noted transplant type, and whether recipient switched to requiring O or O negative cells post transplant given our policy • 52 allogeneic transplants • 29 one donor (PBSC, CBT, or BMT) • 23 double cord blood transplants (DCBT)

  29. Which Transplants Used O-Neg?

  30. Amount of Blood Products Used McCullough J. Collection and use of stem cells; role of transfusion centers in bone marrow transplantation Vox Sang 1994; 67 (Suppl 3):35-42

  31. Do DCBT Patients Use Blood? • Looked at red cell use in 41 DCBT patients • Participants in the platelet dosing study • Counted RBCs used by switched to O- group

  32. Conclusions • Half the O- cells used in non-O- patients went to stem cell transplant patients • Many non-O- DCBT recipients required O- blood post transplant, and they used a substantial number of O- units • Should alert blood supplier of increased O- blood if implementing a DCBT program • Current DCBT programs should alert blood supplier when DCBT procedures increase

  33. Follow-up Study • Wanted to confirm our findings with a higher number of transplants • Contacted cell therapy lab to see what data were available • Cell therapy lab has database of all transplants and ABO types (donor / recipient) • Pulled data from 1st quarter 2005 to 1st quarter 2008 (n = 566 transplants) • Parameters: transplant type (BMT, PBSC, UCBT, DUCBT), ABO of recipient / donor

  34. Total Transplants Per Quarter

  35. ABO Types / Recipients and Donors SDT DUCBT

  36. Mismatches

  37. Red Cells Post-Transplant

  38. Plasma / Platelets Post-Transplant

  39. Results Summary • The majority (76%) of SDTs require O RBCs • Nearly all DUCBTs (91%) require O RBCs • About a third of DUCBTs require O- RBCs (34%), which is approximately double the percent for SDTs (18%) • Approximately 4 times as many DUCBTs (44%) require AB plasma than do SDTs (12%) • In the majority of cases, choosing matched donors would prevent AB and O- use

  40. Discussion • Why is using more O RBCs problematic? • Universal donor, but many can only receive O • O units needed for reference lab cases • Why is using O- RBCs problematic? • Needed for trauma cases / emergency release • Needed for O- females of child bearing age • Needed for neonatal transfusions • What about AB platelets / plasma? • Surgeons want available for emergency trauma • Plasma exchanges on AB patients • Increased work for the blood bank staff

  41. Implications • DUCBT becoming the predominant transplant • TRALI mitigation • Current effort underway to reduce TRALI • Common strategy is to limit female donation • We need female donors to meet CURRENT AB plasma / platelet demand • Platelet additive solutions • Currently the Europeans use platelet additive solutions to remove much of the plasma • DUCBT programs could push this in the US

  42. Implications • Increased pressure on blood suppliers to not only supply lots of blood, rather to supply the KIND of blood needed for the medical care in the community • Pressure to make more effort to ABO match stem cell products when available? • There ARE clinical consequences to ABO mismatch • There are consequences to the blood supply

  43. Conclusions • Due to very real clinical concerns (hemolysis, delayed red cell engraftment, pure red cell aplasia), blood that is compatible with recipients & donors is necessary • DUCBT becoming more common procedure • Multiple blood types involved in DUCBT procedures results in a requirement for an increased number of rare blood products • 34% require O- RBCs • 44% require AB platelets / plasma

  44. Conclusions • The majority of the time the need for rare blood is due to choosing an ABO incompatible stem cell product • DUCBTs put pressure on blood centers to innovate (platelet additive solutions, apheresis, targeted donor programs, engineering of blood products) to meet increasing need for specific blood products • Pressure on transplant physicians and cell therapy labs to carefully choose products

  45. Blood Types in the US http://www.givebloodtoday.org/images/blood%20type%20compat%20chart.jpg

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