Transfusionsmedizinische Versorgung von Patienten nach allogener Blutstammzelltransplantation

Zusammenfassung

Im Rahmen einer allogenen Blutstammzelltransplantation kommt es häufig zu immunhämatologischen Phänomenen, die im Rahmen der Diagnostik und der supportiven Hämotherapie berücksichtigt werden müssen. Durch Diskrepanzen der AB0-Merkmale von Spender und Empfänger können verschiedene Komplikationen auftreten. Die wesentlichsten sind ein verzögertes Engraftment der Erythropoese nach majorinkompatibler Transplantation (sogenannte Pure-red-Cell-Aplasie [PRCA]) und die verzögerte Hämolyse durch Aktivierung von minorinkompatiblen Lymphozyten im Transplantat, das sogenannte Passenger-Lymphocyte-Syndrom (PLS). Durch ein gezieltes immunhämatologisches Monitoring der Patienten können diese Phänomene zeitgerecht erkannt und adäquat therapiert werden. Ein Wechsel im Bereich des Rhesusantigens D ist ebenfalls bei der Hämotherapie allogen transplantierter Patienten zu berücksichtigen, verursacht allerdings nur selten Komplikationen. Hinsichtlich der Thrombozytenversorgung sollte rechtzeitig vor Konditionierungsbeginn eine gezielte Diagnostik von Immunisierungen gegen HLA- (humane Leukozytenantigene) und plättchenspezifische Antigene erfolgen, um die Thrombozytenversorgung mit ausgewählten Spendern in der Aplasiephase zuverlässig gewährleisten zu können. Bei sehr breit und hochtitrig immunisierten Patienten kann eine Immunsuppression mit Rituximab und Immunadsorption vor Transplantation die Inkremente nach Thrombozytensubstitution verbessern und im Falle von einem HLA-Mismatch des Transplantats auch das Engraftment unterstützen.

Abstract

Allogeneic hematopoietic stem cell transplantations frequently cause immunohematological phenomena that require specific diagnostics and transfusion support. Crossing the AB0 blood group barrier between donor and recipient can elicit various complications. The most important challenges are the pure red cell aplasia, PRCA, a delayed red blood cell engraftment that can occur after major AB0 mismatch transplantations, and the passenger lymphocyte syndrome, PLS, a delayed hemolysis due to activated, transplant-derived minor AB0 mismatch lymphocytes. Focussed immunohematological monitoring allows diagnosing these complications permitting therapeutic decisions. RhD factor mismatches have to be considered regarding the transfusion strategy but rarely account for complications. Screening for alloimmunisation against human leukocyte antigens (HLA) or human platelet antigens (HPA) should take place before the conditioning starts to ensure that compatible platelet concentrates will be available during the aplasia phase. In patients with exceptionally high immunization, immunosuppression with rituximab and pre-transplant immunoadsorption may improve the post-transfusion platelet counts and support engraftment in the case of a crossmatch-positive HLA mismatch transplant.

Schlüsselwörter

Blutstammzelltransplantation - Hämolyse - Refraktärzustand bei Thrombozytentransfusion - Transfusionsstrategie

Key words

blood stem cell transplantation - hemolysis - refractoriness to platelet transfusion therapy - transfusion strategy

• Literatur

• 1 Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med 2007; 357: 1472-1475
• 2 Worel N. Transfusionsstrategie und Maßnahmen zur Hämolyseprävention nach allogener Stammzelltransplantation mit AB0-Mismatch. Transfusionsmedizin 2013; 3: 143-146
• 3 Malfuson JV, Amor RB, Bonin P. et al. Impact of nonmyeloablative conditioning regimens on the occurrence of pure red cell aplasia after AB0-incompatible allogeneic haematopoietic stem cell transplantation. Vox Sang 2007; 92: 85-89
• 4 Bolan CD, Childs RW, Procter JL. et al. Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor AB0 incompatibility. Br J Haematol 2001; 112: 787-795
• 5 Worel N, Greinix HT, Keil F. et al. Severe immune hemolysis after minor AB0-mismatched allogeneic peripheral blood progenitor cell transplantation occurs more frequently after nonmyeloablative than myeloablative conditioning. Transfusion 2002; 42: 1293-1301
• 6 Kim-Wanner SZ, Bug G, Steinmann J. et al. Erythrocyte depletion from bone marrow: performance evaluation after 50 clinical-scale depletions with Spectra Optia BMC. J Transl Med 2017; 15: 174-180
• 7 Del Fante C, Scudeller L, Recupero S. et al. Automated red blood cell depletion in AB0 incompatible grafts in the pediatric setting. Transfus Apher Sci 2017; 56: 895-899
• 8 Nussbaumer W, Schweighofer H, Gratwohl A. et al. Transfusion of donor-type red cells as a single preparative treatment for bone marrow transplants with major AB0-incompatibility. Transfusion 1995; 35: 592-595
• 9 Moog R. In vivo adsorption of isoagglutinins with incompatible red blood cell transfusion in stem cell transplant recipients. Transfus Med Hemother 2016; 43: 307
• 10 Stussi G, Muntwyler J, Passweg JR. et al. Consequences of AB0 incompatibility in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2002; 30: 87-93
• 11 Worel N, Greinix HT, Schneider B. et al. Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: A major AB0 mismatch means problems. Transfusion 2000; 40: 543-550
• 12 Schetelig J, Breitschaft A, Kröger N. et al. Cooperative transplantations study group: After major AB0-mismatched allogeneic hematopoietic progenitor cell transplantation, erythroid engraftment occurs later in patients with donor blood group A than donor blood group B. Transfusion 2005; 45: 779-787
• 13 Stussi G, Halter J, Bucheli E. et al. Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins. Haematologica 2009; 94: 239-248
• 14 Bolan CD, Leitmann SF, Griffith LM. et al. Delayed donor red cell chimerism and pure red cell aplasia following AB0-incompatible nonmyeloablative hematopoietic stem cell transplantation. Blood 2001; 98: 1687-1694
• 15 Aung FM, Lichtiger B, Basetti R. et al. Incidence and natural history of pure red cell aplasia in major AB0-mismatched haematopoietic cell transplantation. Br J Hematol 2013; 160: 798-805
• 16 Gmür JP, Burger J, Schaffner A. et al. Pure red cell aplasia of long duration complicating major AB0-incompatible bone marrow transplantation. Blood 1990; 75: 290-295
• 17 Heyll A, Aul C, Runde V. et al. Treatment of pure red cell aplasia after major AB0-incompatible bone marrow transplantation with recombinant erythropoietin. Blood 1991; 77: 906
• 18 Zecca M, de Stefano P, Nobili B. et al. Anti-CD20 monoclonal antibody for the treatment of severe immune-mediated pure red cell aplasia and hemolytic anemia. Blood 2001; 97: 3995-3997
• 19 Poon LM, Koh LP. Successful treatment of isohemagglutinin-mediated pure red cell aplasia after AB0-mismatched allogeneic hematopoietic cell transplant using bortezomib. Bone Marrow Transplant 2012; 47: 870-871
• 20 Fang B, Song Y, Li N. et al. Mesenchymal stem cells for the treatment of refractory pure red cell aplasia after major AB0-incompatible hematopoietic stem cell transplantation. Ann Hematol 2009; 88: 261-266
• 21 Larghero J, Rea D, Esperou H. et al. AB0-mismatched marrow processing for transplantation: results of 114 procedures and analysis of immediate adverse events and hematopoietic recovery. Transfusion 2006; 46: 398-402
• 22 Daniel-Johnson J, Schwartz J. How do I approach AB0-incompatible hematopoietic progenitor cell transplantation?. Transfusion 2011; 51: 1143-1149
• 23 Cohn CS. Transfusion support issues in hematopoietic stem cell transplantation. Cancer Control 2015; 22: 52-59
• 24 Hows J, Beddow K, Gordon-Smith E. et al. Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation. Blood 1986; 67: 177-181
• 25 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
• 26 Bornhäuser M, Ordemann R, Paaz U. Rapid engraftment after allogeneic AB0-incompatible peripheral blood progenitor cell transplantation complicated by severe hemolysis. Bone Marrow Transplant 1997; 19: 295-297
• 27 Oziel-Taieb S, Faucher-Barbey C, Chabannon C. et al. Early and fatal immune hemolysis after so-called “minor” AB0-incompatible peripheral blood stem cell allotransplantation. Bone Marrow Transplant 1997; 19: 1155-1156
• 28 Worel N, Greinix HT, Supper V. et al. Prophylactic red blood cell exchange for prevention of severe immune hemolysis in minor AB0-mismatched allogeneic peripheral blood progenitor cell transplantation after reduced intensity conditioning. Transfusion 2007; 47: 1494-1502
• 29 Snell M, Chau C, Hendrix D. et al. Lack of isohemagglutinin production following minor AB0 incompatible unrelated HLA mismatched umbilical cord blood transplantation. Bone Marrow Transplant 2006; 38: 135-140
• 30 Sandler SG, Han S, Langeberg A. et al. Nonhemolytic passenger lymphocyte syndrome. Transfusion 2017; 57: 2942-2945
• 31 Rosner A, Schetelig J, Bornhäuser M. et al. Irregular alloantibodies and rare red cell phenomena after hematopoietic stem cell transplantation. Transfus Med Hemother 2014; 41 (Suppl. 01) 14
• 32 Cassens U, Eichler H, Klüter H. et al. Stellungnahme der Sektion „Transplantation und Zelltherapie“ zur Transplantation hämatopoetischer Stammzellen mit Blutgruppendifferenz. Transfus Med Hemother 2004; 31: 56-60
• 33 Worel N, Panzer S, Reesink HW. et al. Transfusion policy in AB0-incompatible allogeneic stem cell transplantation. Vox Sang 2010; 98: 455-467
• 34 Tormey CA. Transfusion Support for hematopoietic Stem Cell Transplant Recipients. In: Roback JD, Grossman BJ, Harris T, Hillyer CD. AABB technical Manual, 17th ed. Bethesda: AABB; 2011: 687-705
• 35 Rosner A, Schetelig J, Bornhäuser M. et al. Transfusion strategy in rhesus-mismatched stem cell transplantations in times of scarce D-negative red blood cell supply. Transfus Med Hemother 2016; 43 (Suppl. 01) 61-62
• 36 Bailén R, Kwon M, Perez-Corral AM. et al. Transient hemolysis due to anti-D and anti-A1 produced by engrafted donorʼs lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation. Transfusion 2017; 57: 2355-2358
• 37 Contentin N, Lenain P, Chamouni P. et al. Transient anti rhesus alloantibody produced by graft after non-myeloablative allogeneic stem cell transplant. Transfus Apher Sci 2004; 31: 191-197
• 38 Cid J, Lozano M, Fernandez-Aviles F. et al. Anti-D alloimmunization after D-mismatched allogeneic hematopoietic stem cell transplantation in patients with hematologic diseases. Transfusion 2006; 46: 169-173
• 39 Bashey A, Zhang X, Sizemore CA. et al. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol 2013; 31: 1310-1316
• 40 Hod E, Schwartz J. Platelet transfusion refractoriness. Br J Haematol 2008; 142: 348-360
• 41 Bayer WL, Bodensteiner DC, Tilzer LL. et al. Use of platelets and other transfusion products in patients with malignancy. Semin Thromb Hemost 1992; 18: 380-391
• 42 Juskewitch JE, Norgan AP, De Goey SR. et al. How do I manage the platelet transfusion-refractory patient?. Transfusion 2017; 57: 2828-2835
• 43 Kiefel V, König C, Kroll H. et al. Platelet alloantibodies in transfused patients. Transfusion 2001; 41: 766-770
• 44 Morales-Buenrostro LE, Terasaki PI, Marino-Vázquez LA. et al. “Natural” human leukocyte antigen antibodies found in nonalloimmunized healthy males. Transplantation 2008; 86: 1111-1115
• 45 Greinacher A, Kiefel V, Klüter H. et al. Empfehlungen zur Thrombozytentransfusion der Thrombozytenarbeitsgruppe der DGTI, GTH und DGHO. Transfus Med Hemother 2006; 33: 528-543
• 46 Hoppe JD, Scriba PC, Klüter H. Hrsg. Querschnitts-Leitlinien (BÄK) zur Therapie mit Blutkomponenten und Plasmaderivaten – 4. aktualisierte und überarbeitete Auflage. Köln: Deutscher Ärzte-Verlag; 2014
• 47 Comont T, Tavitian S, Bardiaux L. et al. Platelet transfusion refractoriness in patients with acute myeloid leukemia treated by intensive chemotherapy. Leuk Res 2017; 61: 62-67
• 48 Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med 1997; 337: 1861-1869
• 49 Stanworth SJ, Estcourt LJ, Powter G. et al. A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med 2013; 368: 1771-1780
• 50 Wandt H, Schaefer-Eckart K, Wendelin K. et al. Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study. Lancet 2012; 380: 1309-1316
• 51 Schiffer CA, Bohlke K, Delaney M. et al. Platelet transfusion for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2018; 36: 283-302
• 52 Liu W, Wu D, Hu T. et al. Efficiency of treatment with rituximab in platelet transfusion refractoriness: a study of 7 cases. Int J Clin Exp Med 2015; 8: 14080-140804
• 53 Rosner A, Bornhäuser M, Passauer J. et al. Immunoadsorption in a hyperimmunized patient undergoing mismatched allogeneic haematopoetic stem cell transplantation. EBMT 2011, Poster P713.
• 54 Parissiadis A, Bilger K, Laplace A. et al. [Occurrence of severe, persistent thrombocytopenia following allogeneic bone marrow transplantation, attributable to anti-HPA-1 allo-immunisation of the host]. Transfus Clin Biol 2010; 17: 265-268