Zusammenfassung
1989 wurde von E. Gluckman über die erfolgreiche Nabelschnurblutransplantation bei einem Jungen mit Fanconi-Anämie berichtet. Seither wurden weltweit über 1500 allogene Nabelschnurbluttransplantationen durchgeführt. Dies ist u. a. durch den Aufbau von öffentlichen Nabelschnurblutbanken ermöglicht worden, die kryokonservierte Nabelschnurblutprodukte unverwandter Spender zur Verfügung stellen. Die Nabelschnurbluttransplantation ist allerdings mit spezifischen Risiken behaftet, die ihren Einsatz bisher einschränken. Hauptproblem ist die limitierte Zellmenge, die mit einer lang andauernden Neutropenie und einem erhöhten Risiko für ein Transplantatversagen einhergeht. Aufgrund dieser Probleme wird bisher nur bei etwa 1 - 2 % aller Stammzelltransplantationen im Kindesalter Nabelschnurblut als Stammzellquelle genutzt. Der große Vorteil der Nabelschnurbluttransplantation ist das niedrige Risiko für eine Transplantat-gegen-Wirt-Erkankung (Graft-versus Host Disease [GvHD]), einer der Hauptursachen für die hohe transplantationsassozierte Morbidität und Mortalität insbesondere bei unverwandten Stammzellspendern. Das geringe GvHD-Risiko wird auf die niedrige Dosis transplantierter T-Zellen und die funktionelle Unreife der neonatalen Lymphozyten zurückgeführt. Weiterer Vorteil der Nabelschnurbluttransplantation ist die rasche Verfügbarkeit des Stammzellprodukts. Basierend auf den Erfahrungen der allogenen Nabelschnurbluttransplantation werden die Indikationen zur „gerichteten” und „ungerichteten” Nabelschnurblutspende diskutiert.
Abstract
In 1989 E. Gluckman reported the successful cord blood transplantation in a boy with Fanconi anemia. Since then more than 1500 allogeneic cord blood transplantations have been performed worldwide. This has been possible because non-profit cord blood banks have been established that provide cryopreserved cord blood products from unrelated donors. However, cord blood transplantation is associated with specific risks that have sofar limited its more widespread use. Its main problem is the limited stem cell dose that is associated with a long aplasia and a high rate of engraftment failure. Therefore, cord blood is used as the stem cell source in only about 1 - 2 % of stem cell transplantations in childhood. The main advantage of cord blood transplantation lies in its low risk for graft-versus-host-disease (GvHD), one of the major causes for posttransplant morbidity and mortality particularily with unrelated stem cell donors. The low risk for GvHD is attributed to the low number of transplanted T cells and their functional immaturity. Another advantage of cord blood transplantation lies in the imediate availability of the cord blood units. Based on the experiences with allogeneic cord blood transplantation the indications for cord blood donation will be discussed.
Schlüsselwörter:
Nabelschnurblut - Stammzelltransplantation - Nabelschnurblutspende
Key words:
Cord blood - Stem cell transplantation - Cord blood donation
Literatur
-
1
Work Group on Cord Blood Banking .
Cord blood banking for potential future transplantation: Subject review. American Academy of Pediatrics.
Pediatrics.
1999;
104
116-118
-
2
Wissenschaftlicher Beirat der Bundesärztekammer .
Richtlinien zur Transplantation von Stammzellen aus Nabelschnurblut.
Dt. Ärztebl.
1999;
94
A1297-1304
-
3
Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Artistei C, Latini P, Reisner Y, Martelli M F.
Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype.
N Engl J Med.
1998;
339
1186-1193
-
4
Bader P, Hancock J, Kreyenberg H, Goulden N J, Niethammer D, Handgretinger R, Oakhill A, Steward C G, Beck J F, Klingebiel T.
Minimal residual disease status prior to allogeneic stem cell transplantation (allo-SCT) in children with ALL has a profound impact on post-transplant outcome.
Bone Marrow Transpl.
2001;
27
(1)
S54
-
5
Bader P, Klingebiel T, Schaudt A, Theurer-Mainka U, Handgretinger R, Lang P, Niethammer D, Beck J F.
Prevention of relapse in pediatric patients with acute leukemias and MDS after allogeneic SCT by early immunotherapy initiated on the basis of increasing mixed chimerism: a single center experience of 12 children.
Leukemia.
1999;
13
2079-2086
-
6
Barker J N, Davies S M, DeFor T, Ramysay N KC, Weisdorf D J, Wagner J E.
Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis.
Blood.
2001;
97
2957-2961
-
7
Barker J N, Weisdorf D J, DeFor T E, Davies S M, Verfaille C M, Wagner J E.
Impact of multiple unit unrelated donor umbilical cord blood transplantation in adults: preliminary analysis of safety and efficacy.
Blood.
2001;
11
666a
-
8
Broxmeyer H E, Douglas G W, Hangoc G, Cooper S, Bard J, English D, Arny M, Thomas L, Boyse E A.
Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.
Proc Natl Acad Sci USA.
1989;
86
3828-3832
-
9
Cairo M S, Wagner J E.
Placental and/or umbilical cord blood: An alternative sourc eof hematopoietic stem cells for transplantation.
Blood.
1997;
90
4665-4678
-
10
Carow C E, Hangoc G, Broxmeyer H E.
Human multipotential progenitor cells (CFU-GEMM) have extensive replating capacity for secondary CFU-GEMM: an effect enhanced by cord blood plasma.
Blood.
1993;
18
942-949
-
11
Dallorso S, Manzitti C, Morreale G, Faraci M.
High dose therapy and autologous hematopoietic stem cell transplantation in poor risk solid tumors of childhood.
Haematologica.
2000;
85
66-70
-
12
Eyrich M, Lang P, Lal S, Bader P, Handgretinger R, Klingebiel T, Niethammer D, Schlegel P G.
A prospective analysis of the pattern of immune reconstitution in a paediatric cohort following transplantation of positively selected human leucocyte antigen-disparate haematopoietic stem cells form parental donors.
Br J Haematol.
2001;
114
422-432
-
13
Fruchtman S M, Isola L, Hurlet A, Dracker R, Richard S, Singh H, Goldman B, Emre S.
Autologous cord blood infusion for severe aplastic anemia (SAA).
Blood.
2001;
98
687a
-
14
Gluckman E.
Hematopoietic stem-cell transplants using umbilical-cord blood (editorial).
N Engl J Med.
2001;
344
1860-1861
-
15
Gluckman E, Broxmeyer H E, Auerbach A D, Friedman H S, Douglas G W, Devergie A, Esperou H, Thierry D, Socie G, Lehn P, Cooper S, English D, Kurtzberg J, Bard J, Boyse E A.
Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling.
N Engl J Med.
1989;
321
1174-1178
-
16
Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte J P, Fernandez M, Chastang C.
Outcome of cord-blood transplantation from related and unrelated donors.
N Engl J Med.
1997;
337
373-381
-
17
Gryn J, Harris D T, Shadduck R K, Lister J, Raymond J, Ziegler Z, Lech J, Thimmons M.
Multiple unmatched unrelated umbilical cord units (MUCs) for adult allogeneic transplantation.
Blood.
2001;
11
666a
-
18
Hakenberg P, Kogler G, Wernet P.
NETCORD: a cord blood allocation network.
Bone Marrow Transpl.
1998;
22
(1)
S17-18
-
19
Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A, Bader P, Schlegel P G, Greil J, Stachel D, Herzog R J, Niethammer D.
Megadose transplantation of purified peripheral blood CD34+ progenitor cells from HLA-mismatched parental donors in children.
Bone Marrow Transpl.
2001;
27
777-783
-
20
Hows J M, Bradley B A, Marsh J CW, Luft T, Coutinho L, Testa N G, Dexter T M.
Growth of human umbilical-cord blood in longterm haemopoietic cultures.
Lancet.
1992;
340
73-76
-
21
Knechtli C JC, Goulden N J, Hancock J P, Gandage V LG, Harris E L, Garalnd R J, Jones C G, Rowbottom A W, Hunt L P, Green A F, Clarke E, Lankester A W, Cornish J M, Pamphilon D H, Steward C G, Oakhill A.
Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia.
Blood.
1998;
92
4072-4079
-
22
Kogler G, Nürnberger W, Fischer J, Niehues T, Somville T, Göbel U, Wernet P.
Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia.
Bone Marrow Transpl.
1999;
24
397-403
-
23
Kogler G, Somville T, Göbel U, Hakenberg P, Knipper A, Fischer J, Adams O, Krempe C, McKenzie C, Rüttgers H, Meier W, Bellmann O, Streng H, Ring A, Rosseck U, Rocha V, Wernet P.
Haematopoietic transplant potential of unrelated and related cord blood: the first six years of the EUROCORD/NETCORD Bank Germany.
Klin Pädiatr.
1999;
211
224-232
-
24
Korbling M, Anderlini P.
Peripheral blood stem cell versus bone marrow allotransplantation: does the source of hematopoietic stem cells matter?.
Blood.
2001;
98
2900-2908
-
25
Kurtzberg J, Laughlin M, Graham M L, Smith C, Olson J F, Halperin E C, Ciocci G, Carrier C, Stevens C E, Rubinstein P.
Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.
N Engl J Med.
1996;
335
157-166
-
26
Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissmann I L, Grompe M.
Purified hematopoietic stem cell can differentiate into hepatocytes in vivo.
Nature Med.
2000;
6
1229-1234
-
27
Laughlin M J, Barker H, Bambach B, Koc O N, Rizzieri D A, Wagner J E, Gerson S L, Lazarus H M, Cairo M, Stevens C E, Rubinstein P, Kurtzberg J.
Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.
N Engl J Med.
2001;
344
1815-1822
-
28
Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M, Messina C, Ortega J, Badell-Sera I, Plouvier E, Souillet G, Jouet J-P, Pasquini R, Ferreira E, Garnier F, Gluckman E.
Factors associated with outcome after cord blood transplantation in children with acute leukemia.
Blood.
1999;
93
3662-3671
-
29
Mayani H, Lansdorp P M.
Biology of human umbilical cord blood-derived hematopoietic stem/progenitor cells.
Stem Cells.
1998;
16
153-165
-
30
Mezey E, Chandross K J, Harta G, Maki R A, McKercher S R.
Touring blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow.
Science.
2000;
290
1779-1782
-
31
Müller S M, Schulz A S, Reiss U M, Schwarz K, Schreiner T, Wiesneth M, Debatin K-M, Friedrich W.
Definition of a critical T cell threshold for prevention of GVHD after HLA non-identical PBPC transplantation in children.
Bone Marrow Transpl.
1999;
24
575-581
-
32
Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson S M, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine D M, Leri A, Anversa P.
Bone marrow cells regenerate infarcted myocardium.
Nature.
2001;
410
701-705
-
33
Ottinger H D, Müller C R, Goldmann S F, Albert E, ARnold R, Beelen D W, Blascyk R, Bunjes D, Casper J, Ebell W, Ehninger G, Eiermann T, Einsele H, Fauser A, Ferencik S, Finke J, Hertenstein B, Heyll A, Klingenbiel T, Knipper A, Kremens B, Kolb H J, Kolbe K, Lenartz E, Lindemann M, Müller C A, Mytilineos J, Niederwieser D, Runde V, Sayer H, Schaefer U W, Schmitz N, Schröder S, Schulze-Rath R, Schwerdtfeger R, Siegert W, Thiele B, Zander A R, Grosse-Wilde H.
Second German consensus on imunogenetic donor search for allotransplantation of hematopoietic stem cells.
Ann Hematol.
2001;
80
706-714
-
34
Peters C, Matthes-Martin S, Fritsch G, Holter W, Lion T, Witt V, Hocker P, Fischer G, Dieckmann K, Handgretinger R, Klingebiel T, Gadner H.
Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment.
Leukemia.
1999;
13
2070-2078
-
35
Reyes M, Lund T, Lenvik T, Anguiar D, Koodie L, Verfaille C M.
Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.
Blood.
2001;
98
2615-2625
-
36
Rocha V, Cornish J, Sievers E L, Filipovich A, Locatelli F, Peters C, Remberger M, Michel G, Arcese W, Dallorso S, Tiedemann K, Busca A, Chan K-W, Kato S, Ortega J, Vowels M, Zander A, Souillet G, Oakill A, Woolfrey A, Pay A L, Green A, Garnier F, Ionescu I, Wernet P, Sirchia G, Rubinstein P, Chevret S, Gluckman E.
Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.
Blood.
2001;
97
2962-2971
-
37
Rocha V, Wagner J E, Sobocinski K A, Klein J P, Zhang M-J, Horowitz M M, gluckman E.
Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling.
N Engl J Med.
2000;
342
1846-1854
-
38
Rubinstein C, Carrier C, Scardavou A, Kurtzberg J, Adamson J, Migliaccio A R, Berkowitz R L, Cabbad M, Dobrila N L, Taylor P E, Rosenfield R E, Stevens C E.
Outcomes among 562 recipients of placental-blood transplants from unrelated donors.
N Engl J Med.
1998;
339
1565-1577
-
39
Volpi I, Perruccio K, Tosti A, Capanni M, Ruggeri L, Posati S, Aversa F, Tabilio A, Romani L, Martelli M F, Verlardi A.
Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants.
Blood.
2001;
97
2514-2521
-
40
Vormoor J, Lapidot T, Pflumio F, Risdon G, Patterson B, Broxmeyer H E, Dick J E.
Immature human cord blood progenitors engraft and proliferative to high levels in severe combined immunodeficient mice.
Blood.
1994;
83
2489-2497
-
41
Wiemels J L, Cazzaniga G, Daniotti M, Eden O B, Addison G M, Masera G, Saha V, Biondi A, Greaves M F.
Prenatal orogin of acute lymphoblastic leukaemia in children.
Lancet.
1999;
354
1499-1503
Dr. med. Josef Vormoor
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