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Topic: ABO Incompatibility and Cord Blood Transplantation

Question:

A physician enquires: Are there any issues regarding donor-recipient ABO incompatibility in cord blood transplantation that are different than with marrow or peripheral blood hematopoietic cell transplants?

Response:

There is little emphasis on donor-recipient ABO-compatibility in reports of cord blood transplantation. Although significant adverse effects have frequently been reported after ABO incompatible BM/PBSC transplants, there are no publications devoted to such complications after cord blood transplants.

There may be critical differences in cord bloods which mitigate the adverse effects of ABO incompatibility. However, the one complication one would certainly expect to occur  regardless of the source of stem cells is delayed hematopoiesis (1), particularly delayed erythropoiesis (2-16) following major ABO incompatibility (e.g., donor, group A; recipient, group O). This is true because the cause of the delayed onset of hematopoiesis is the reaction of the ABO-antibody in the patient’s serum versus newly engrafting hematopoietic cells. One would expect the antibody to react with the engrafting cells regardless of their source.

 The passenger lymphocyte syndrome (17), which occurs following minor ABO-incompatible transplants (e.g., donor group O, patient group A) and which occasionally causes massive (18-24) and even fatal hemolysis (21), has not been reported following cord blood transplantation. This may be due to the fact that the incidence and severity of the syndrome is related to the lymphoid content of the graft (25-27). The higher lymphoid content of PBSCs compared to conventional marrow harvests (28;29) may be the explanation for the higher incidence and greater severity of the passenger lymphocyte syndrome after PBSC transplantation (20-23;27;30-34).

 Also, reduced intensity regimens may be associated with a higher incidence of delayed erythropoiesis (9;35;36) and  the passenger lymphocyte syndrome (27;34). Such regimens are being used increasingly in cord blood transplants. One wonders if these complications will be observed in cord blood transplants when reduced intensity regimens are used.

Finally, some reported data suggest that the incidence of acute GVHD is higher in patients receiving an ABO incompatible marrow graft, especially with minor ABO incompatibility (37-39). There are no comparable data regarding cord blood transplants.

Reference List 

1. Blacklock HA, Gilmore MJ, Prentice HG, Hazlehurst GR, Evans JP, Ma DD et al. ABO-incompatible bone-marrow transplantation: Removal of red blood cells from donor marrow avoiding recipient antibody depletion. Lancet 1982; 2:1061-1064.

2. Hows JM, Chipping PM, Palmer S, Gordon Smith EC. Regeneration of peripheral blood cells following ABO incompatible allogeneic bone marrow transplantation for severe aplastic anaemia. Br J Haematol 1983; 53:145-151.

3. Petz LD. Immunohematologic problems associated with bone marrow transplantation. Transfus Med Rev 1987; 1:85-100.

4. Gmur J, Burger J, Schaffner A, et al. Pure red cell aplasia of long duration complicating major ABO-incompatible bone marrow transplantation. Blood 1990; 75:290-295.

5. Sniecinski IJ, Oien L, Petz LD, et al. Immunohematologic consequences of major ABO-mismatched bone marrow transplantation. Transplantation 1988; 45:530-534.

6. Bar BMAM, Van Dijk BA, Schattenberg A, et al. Erythrocyte repopulation after major ABO incompatible transplantation with lymphocyte-depleted bone marrow. Bone Marrow Transplant 1995; 16:793-799.

7. Lasky LC, Warkentin PI, Kersey JH, Ramsay NK, McGlave PB, McCullough J. Hemotherapy in patients undergoing blood group incompatible bone marrow transplantation. Transf 1983; 23:277-285. 

8. Bensinger WI, Buckner CD, Thomas ED, Clift RA. ABO-incompatible marrow transplants. Transplantation 1982; 33:427-429.

9. Bolan CD, Leitman SF, Griffith LM, Wesley RA, Procter JL, Stroncek DF 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.

10. Yang MH, Hsu HC. Pure red cell aplasia after ABO-incompatible allogeneic stem cell transplantation in severe aplastic anemia with response to steroids: a case report and literature review. Ann Hematol 2001; 80:299-301.

11. Santamaria A, Sureda A, Martino R, Domingo-Albos A, Muniz-Diaz E, Brunet S. Successful treatment of pure red cell aplasia after major ABO- incompatible T cell-depleted bone marrow transplantation with erythropoietin. Bone Marrow Transplant 1997; 20:1105-1107.

12. Bierman PJ, Warkentin P, Hutchins MR, Klassen LW. Pure red cell aplasia following ABO mismatched marrow transplantation for chronic lymphocytic leukemia: response to antithymocyte globulin. Leuk Lymphoma 1993; 9:169-171.

13. Benjamin RJ, Connors JM, McGurk S, Churchill WH, Antin JH. Prolonged erythroid aplasia after major ABO-mismatched transplantation for chronic myelogenous leukemia. Biol Blood Marrow Transplant 1998; 4:151-156.

14. Sniecinski I, O'Donnell MR. Hemolytic Complications of Hematopoietic Cell Transplantation. In: Thomas ED, Blume KG, Forman SJ, editors. Hematopoietic Cell Transplantation. Malden, MA: Blackwell Science, Inc., 1999: 674-684.

15. Lee JH, Lee JH, Choi SJ, Kim S, Seol M, Kwon SW et al. Changes of isoagglutinin titres after ABO-incompatible allogeneic stem cell transplantation. Br J Haematol 2003; 120:702-710.

16. Marmont AM, Damasio EE, Bacigalupo A, Giordano D, Rossi E, Reali G et al. A to O bone marrow transplantation in severe aplastic anaemia: dynamics of blood group conversion and demonstration of early dyserythropoiesis in the engrafted marrow. Br J Haematol 1977; 36(\):511-518.

17. Hows J, Beddow K, Gordon Smith E, Branch DR, Spruce W, Sniecinski I et al. Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation. Blood 1986; 67:177-181.

18. Gajewski JL, Petz LD, Calhoun L, O'rourke S, Landaw EM, Lyddane NR et al. Hemolysis of transfused group O red blood cells in minor ABO-incompatible unrelated-donor bone marrow transplants in patients receiving cyclosporine without posttransplant methotrexate. Blood 1992; 79:3076-3085.

19. Greeno EW, Perry EH, Ilstrup SJ, Weisdorf DJ. Exchange transfusion the hard way:  Massive hemolysis following transplantation of bone marrow with minor ABO incompatibility. Transf 1996; 36:71-74.

20. Laurencet FM, Samii K, Bressoud A, Tajeddin M, Easton J, Stelling MJ et al. Massive delayed hemolysis following peripheral blood stem cell transplantation with minor ABO incompatibility. Hematol Cell Ther 1997; 39:159-162.

21. Oziel-Taieb S, Faucher-Barbey C, Chabannon C, Ladaique P, Saux P, Gouin F et al. Early and fatal immune haemolysis after so-called 'minor' ABO-incompatible peripheral blood stem cell allotransplantation. Bone Marrow Transplantation 1997; 19:1155-1156.

22. Toren A, Dacosta Y, Manny N, et al. Passenger B-lymphocyte-induced severe hemolytic disease after allogeneic peripheral blood stem cell transplantation. Blood 1996; 87:843-844.

23. Broketa G, Simpson JK, Hammert L, Ball E. Delayed hemolysis after minor ABO mismatched peripheral blood stem cell transplantation. Transf 1997; 37:37S.

24. Tiplady CW, Fitzgerald JM, Jackson GH, Conn JS, Proctor SJ. Massive haemolysis in a group A recipient of a group O peripheral blood stem cell allogeneic transplant. Transfus Med 2001; 11:455-458.

25. Ramsey G. Red cell antibodies arising from solid organ transplants. Transf 1991; 31:76-86.

26. Magrin GT, Street AM, Williams TJ, Esmore DS. Clinically significant anti-A derived from B lymphocytes after single lung transplantation. Transplantation 1993; 56:466.

27. Bolan CD, Childs RW, Procter JL, Barrett AJ, Leitman SF. Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility. Br J Haematol 2001; 112:787-795.

28. Pan L, Delmonte J, Jr., Jalonen CK, Ferrara JL. Pretreatment of donor mice with granulocyte colony-stimulating factor polarizes donor T lymphocytes toward type-2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood 1995; 86:4422-4429.

29. Korbling M, Huh YO, Durett A, Mirza N, Miller P, Engel H et al. Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy- 1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease. Blood 1995; 86:2842-2848.

30. Salmon JP, Michaux S, Hermanne JP, Baudoux E, Gerard C, Sontag-Thull D et al. Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation. Transf 1999; 39:824-827.

31. Bornhauser M, Ordemann R, Paaz U, Schuler U, Kompf J, Holig K et al. Rapid engraftment after allogeneic ABO-incompatible peripheral blood progenitor cell transplantation complicated by severe hemolysis. Bone Marrow Transplant 1997; 19:295-297.

32. Delamaire M, le Berre CI, Dauriac C, et al. Fatal hemolysis following allogeneic peripheral blood stem cells (PBSC) transplantation. Vox Sanguinis 74 (Suppl), 1533. 1998. Ref Type: Abstract

33. Rowley SD. Hematopoietic stem cell transplantation between red cell incompatible donor-recipient pairs. Bone Marrow Transplant 2001; 28:315-321.

34. Worel N, Greinix HT, Keil F, Mitterbauer M, Lechner K, Fischer G et al. Severe immune hemolysis after minor ABO-incompatible allogeneic peripheral blood stem cell transplantation occurs more frequently after nonmyeloablative than myeloablative conditioning. Transf 2002; 42:1293-1301.

35. Peggs KS, Morris EC, Kottaridis PD, Geary J, Goldstone AH, Linch DC et al. Outcome of major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation may be influenced by conditioning regimen. 99 ed. 2002.

36. Veelken H, Wasch R, Behringer D, Bertz H, Finke J. Pure red cell aplasia after allogeneic stem cell transplantation with reduced conditioning. Bone Marrow Transplant 2000; 26:911-915.

37. Barone B, Cordeiro de Paiva TM, da Silva Bouzas LF, Barbosa ML, Maciel CM, Paraguassu-Braga FH et al. ABO system incompatibility and graft versus host disease (GVHD) frequency in bone marrow transplanted patients. Blood 98, 374b. 2001. Ref Type: Abstract

38. Stussi G, Seebach L, Muntwyler J, Schanz U, Gmur J, Seebach JD. Graft-versus-host disease and survival after ABO-incompatible allogeneic bone marrow transplantation: a single-centre experience. Br J Haematol 2001; 113:251-253.

39. Stussi G, Muntwyler J, Passweg JR, Seebach L, Schanz U, Gmur J et al. Consequences of ABO incompatibility in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2002; 30:87-93.

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