Transfusion and Stem Cell and Solid Organ Transplantation: Issues and Solutions

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1 Transfusion and Stem Cell and Solid Organ Transplantation: Issues and Solutions Hedyeh Shafi, M Objectives: escribe the different phases of transfusion support in hematopoietic stem cell transplantation escribe challenges associated with ABO-incompatible hematopoietic stem cell transplantation Understand the mechanism for Passenger Lymphocyte Syndrome efinitions Hematopoietic Stem Cell(HSC)- immature cells that have the potential to divide and also mature into all hematopoietic cell Hematopoietic Progenitor Cell(HPC)- More mature cells that initially maintain the capacity to renew, but also become committed to a cell line type (eg. Myeloid or lymphoid lineage) Shafi, Heidi 1

2 efinitions Hematopoietic Stem Cell Transplant (HSCT)- the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow (HPC-M), peripheral blood (HPC-A), or umbilical cord blood (HPC-C), from a donor to a recipient. Autologous- the patient's own stem cells are used Allogeneic- the stem cells come from a donor efinitions Engraftment- dynamic cellular process of stem cells homing and differentiating in a recipient (should occur within 100 days of transplant) Graft Failure- Loss of function or failure to gain function of the transplanted organ or tissue Allogeneic onor Compatibility Human Leukocyte Antigen (HLA) compatibility- most important HLA-A, HLA-B, HLA-C, HLA-RB1 HPCs express HLA Antigens ABO incompatible transplants are possible HPCs don t express ABO Antigens Shafi, Heidi 2

3 Compatibility for HSCT by ABO Blood Group of onor and Recipient: Szczepiorkowski ZM. Core Principles in Cellular Therapy. Bethesda, M, AABB, 2008: Compatibility for HSCT by ABO Blood Group of onor and Recipient: Recipient ABO Group onor ABO Group O A B AB O Identical Major Major Major A Minor Identical Bidirectional Major B Minor Bidirectional Identical Major AB Minor Minor Minor Identical Phase I - from the time patient/recipient is prepared for HPC transplant until initiation of transplant Phase II - from the initiation of chemotherapy until engraftment Phase III - after engraftment; when the front and back type of the patient/recipient is consistent with donor's ABO group Shafi, Heidi 3

4 Phase I - from the time patient/recipient is prepared for HPC transplant until initiation of transplant Prevent HLA immunization (leukocyte-reduced products) Prevent Graft vs. Host isease- Irradiated blood products CMV-negative products* Transfuse all components per recipient ABO group* For incompatible transplants- consider giving type O PRBCs or recipient type products Phase II - from the initiation of chemotherapy until engraftment: Prevent HLA immunization (leukocyte-reduced products) Prevent Graft vs. Host isease- Irradiated blood products CMV-negative products For ABO-mismatched transplants transfuse all components per following table Recipeint Type onor Type Red Cell Type FFP/PLT Type O A O A, AB O B O B, AB O AB O AB A AB A,O AB B AB B,O AB A O O A, AB B O O B, AB AB O O AB AB A A, O AB AB B B, O AB A B O AB B A O AB Shafi, Heidi 4

5 Major ABO Incompatibility: Issues: Immediate: Hemolysis of the infused donor red cells within the graft elayed: Hemolysis of red cells produced by engrafted marrow (recipient ABO antibodies may persist 3-4 mo) elayed onset of erythropoiesis (40-60 days) Pure red-cell aplasia Major ABO Incompatibility: Solutions: Red cell removal from the graft during collection or processing Red cell depletion (HPC-M, HPC-C, HPC-A (only a few red cells)) Cryopreservation (HPC-C) ABO antibody reduction using apheresis Rarely needed Transfuse components compatible with donor and recipient Red Cell epletion Method Advantage isadvantage Hetastarch Errors other than leakage are recoverable Not extremely operator dependent Closed system Non-toxic Hetastarch with centrifugation Same advantages as hetastarch alone Rapid processing for time critical procedures Good for smaller volumes Cell Washer Closed system Errors other than leakages are recoverable ensity Gradient Common equipment Open system Long sedimentation period Citrate-containing anticoagulants interfere with rouleaux formation Increased risk of bag breakage due to centrifugation ifficult for large volume products Citrate-containing anticoagulants interfere with rouleaux formation Time Older technology Requires investment in equipment Usually reserved for research use or processing of products under an IN, not routine clinical use Operator dependent Known toxicity to cells Cell Washer with ensity Gradient Closed system Large volume Errors other than leakages are recoverable Time Older technology Requires investment in equipment SEPAX II Automated Closed system Good Recovery Can be used for both RBC and plasma depletion Requires investment in equipment Machine processes one unit at a time Adapted from RBC epletion by eborah L. Griffin, MS Shafi, Heidi 5

6 Minor ABO Incompatibility: Issues: Immediate: Hemolysis of recipient s red cells upon infusion of donor ABO antibodies within the graft Mild and Self-limited elayed: Hemolysis (5-16 days after infusion of HPCs), due to rapid generation of antibodies by donor lymphocytes (passenger B-cells) Minor ABO Incompatibility: Solutions: Plasma depletion Recipient's dilution of red cells by RBC exchange using donor compatible RBCs Transfuse components with plasma which is compatible with donor and recipient RBCs Bidirectional ABO Incompatibility: Issues: Immediate: Hemolysis caused by donor and/or recipient s red cells antibodies elayed: Hemolysis caused by donor and/or recipient s red cells antibodies elayed engraftment of RBCs Pure red cell aplasia Shafi, Heidi 6

7 Bidirectional ABO Incompatibility: Solutions: Combination of practice used in minor and major ABO incompatibility: Red cell depletion Plasma depletion Incompatibility Related to Non-ABO Antigens Less frequent than those related to ABO Antigens Red Cell Antibodies in Recipient Red Cell Antibodies in onor (less common) Phase III after engraftment; when the front and back type of the patient/recipient is consistent with donor's ABO group Prevent HLA immunization (leukocyte-reduced products) Prevent Graft vs. Host isease- Irradiated blood products CMV-negative products Transfuse all components per donor ABO group Shafi, Heidi 7

8 Red blood cells: 7g/dl in stable, non-postoperative adult HSCT recipient 8g/dl for adults with preexisting heart disease and/or at risk of end organ damage Platelets: 10,000 /ul for prophylaxis 20,000/uL in febrile patients* 50,000/uL in bleeding patients Platelet Refractoriness: Issues: HLA-alloimmunization is observed in 7% to 34% of hematooncologic patients Increases platelet transfusion requirements Increases risk of delayed bleeding post transplant Solutions: Transfusion of antigen-negative, cross-matched or HLAmatched platelets Prevention is the best solution! Shafi, Heidi 8

9 Plasma and Cryoprecipitate: No specific recommendations Solid Organ Transplantation and Transfusion A 57 yo male (blood type B-) with end stage liver disease receives a liver transplant from a O- deceased donor. He has a relatively uneventful postoperative period, however by postoperative day 15 his total bilirubin has slowly increased to 8.2 mg/dl. Clinical team is concerned and orders a few more tests, and consults Transfusion Medicine. What do you think are their main concerns? Shafi, Heidi 9

10 Solid Organ Transplantation In 2014: 29, 533 transplants in US Solid Organ Transplantation ABO compatibility is the most important ABO incompatible transplants are possible (eg. Kidney transplants) Require desensitization of recipient through plasma exchange and immunosuppressive therapies Use of A2 donor organs Transfusion Support in Solid Organ Recipients Prevent HLA immunization (leukocyte-reduced products) CMV-negative products for CMV negative recipients receiving CMV-negative organs Transfusion requirements: Liver>Heart>Kidney Shafi, Heidi 10

11 Transfusion Support in Solid Organ Recipients Liver Transplants Red Cells, Plasma and Platelets Rh () type switch Alloimmunization to RBC antigens Use antigen (-) units at the beginning and end If necessary use antigen (+) units in the middle Inventory management: For A and O patients use ABO identical RBCs For AB patients, consider using Type A RBCs For B patients, consider using Type O RBCs Communication between Transplant team and Blood bank is Key! Transfusion Strategy for ABO Mistmatched Solid Organ Transplants Recipient onor RBCS Plasma/Platelets O A B AB A O A, AB B O B, AB AB O AB B O AB AB A,O AB O O A, AB A O AB AB B,O AB O O B, AB A A,O AB B B,O AB O O AB A 57 yo male (blood type B-) with end stage liver disease receives a liver transplant from a O- deceased donor. He has a relatively uneventful postoperative period, however by postoperative day 9 his total bilirubin has slowly increased to 8.2 mg/dl. Clinical team is concerned and orders a few more tests, and a consult from Transfusion Medicine. What do you think are their main concerns? hemoglobin level is 5.8g/dl Shafi, Heidi 11

12 R O- donor RBCs onor B-lymphocytes Recipient B- RBCs onor anti-b antibodies 1-2 weeks later R R R R R R Passenger Lymphocyte Syndrome (PLS) Immune-mediated hemolysis following ABO mismatched solid organ and/or bone marrow transplantation Most often seen in transplantation with a minor ABO mismatch Mediated by donor B-lymphocytes Occurs 7-10 days post transplantation Usually resolves with 4 weeks (some report cases up to 3 mos) Patient may require transfusions and steroids To avoid PLS, transfuse O RBCs in the post transplant period PLS Involving Non-ABO Antibodies A 58 yo male (blood type O+) with CML received a stem cell transplant from A- donor who had an identifiable anti-. Stem cell product was plasma reduced prior to infusion. On post transplant day 8, he developed significant hemolysis and the antibody screen and direct antiglobulin test were positive. Post Transplant ay Hemoglobin (g/dl) LH (IU) Total Bilirubin (mg/dl) Antibody Screen irect Antiglobulin Test Eluate Negative Negative Not one 4 Negative Negative Not one Positive Positive Anti Positive Positive Anti- Anti- was still present 12 months after the transplant. Transfus Med Hemother Apr;41(2): Shafi, Heidi 12

13 References: 1. Szczepiorkowski ZM. Core Principles in Cellular Therapy. Bethesda, M, AABB, 2008: Cohn CS, Transfusion support issues in hematopoietic stem cell transplantation. Cancer Control Jan;22(1): Cunard R, Marquez II, Ball E, Nelson CL, Corringham S, Clopton P, Sanchez AP, Lane T, Ward M. Prophylactic red blood cell exchange for ABO-mismatched hematopoietic progenitor cell transplants. Transfusion Jul;54(7): Solves P, Mirabet V, Roig R. Volume reduction in routine cord blood banking. Curr Stem Cell Res Ther ec;5(4): Bonstein L 1, Stemer G, ann EJ, Zuckerman T, Fineman R, Haddad N. Alloimmune platelet transfusion refractoriness circumvented by allogeneic stem cell transplantation. Transfusion May;53(5): Romero S, Solves P, Lancharro A, Cano I, Moscardó F, Carpio N, Sanz MA. Passenger lymphocyte syndrome in liver transplant recipients: a description of 12 cases. Blood Transfus July;13(3): Squires JE. Passenger Lymphocyte Syndrome: A Case Report Involving Non-ABO Antibodies. Transfus Med Hemother Apr;41(2): Fung MK, editor. Technical Manual, 18 th ed. Bethesda, M: American Association of Blood Banks; Shafi, Heidi 13