Abstract
To evaluate longtime survival after matched unrelated donor (MUD) transplantation
a group of patients (n = 10) with intensified GVHD prophylaxis were compared to patients
receiving matched sibling (MSD) transplantation (n = 10); all transplantations were
done between 1989 and 1995 in the same institution. A murine monoclonal antibody against
CD25 was assessed in addition to standard GVHD prophylaxis for reducing GVHD in children
with advanced leukemia after MUD BMT (group I). We compared the incidence of GVHD,
relapse and survival under prophylaxis with either anti-CD25 (group I, n = 10) or
MSD BMT without anti-CD25 (group II, n = 10) with respect to known risk factors of
transplant related morbidity, mortality and outcome. 3/10 leukemia patients in both
groups were in CR3 or in relapse at time of transplant. Whereas incidence of acute
GVHD grade III and IV was significantly higher in group I compared to group II (0.4
vs. 0.0), no differences in engraftment, or chronic GVHD were seen between both groups.
In addition, overall (0.5 vs. 0.6) and leukemia free survival (0.5 vs. 0.6) was not
different after 8 respectively 10 years from transplant. Murine anti-CD25 therapy
may have contributed to matching outcome of MUD vs. MSD marrow transplants in children
with advanced leukemia. In conclusion, the use of anti-CD25 in modulation of CD25+
regulatory and effector T cells in allo- and leukemia recognition merrits further
exploration of its potential to improve both tolerance and leukemia control. Since
the outcome of children with leukemia that received intensified GVHD prophylaxis in
MUD BMT was similar to children with MSD transplants, MUD BMT has to be considered
as an equivalent therapeutic option for patients, who have no HLA-identical sibling
donor.
Zusammenfassung
Das Überleben von Patienten nach allogener unverwandter Stammzelltransplantation (KMT)
wird wesentlich durch das Auftreten einer Spender-gegen-Empfänger-Krankheit (GVHD)
beeinflusst. Um das Langzeitüberleben von Kindern und Jugendlichen nach HLA-identischer
unverwandter (MUD) KMT zu untersuchen, wurden 10 dieser zwischen 1989 und 1995 transplantierten
Patienten mit 10 Patienten nach einer HLA-identischen verwandten (MSD) Knochenmarktransplantation
verglichen. Zusätzlich zur Standard-GVHD-Prophylaxe erhielt die MUD-Gruppe einen Mausantikörper
gegen CD25 (Inolimomab). Die beiden Gruppen wurden hinsichtlich Stammzellart, HLA-Identität,
Remissionsstadium und Erkrankung in Bezug auf die transplantationsbedingte Mortalität
und Morbidität verglichen. Während die Inzidenz der akuten GVHD Grad III und IV signifikant
höher in der MUD-Gruppe war (0,4 vs 0,0), fanden sich keine Unterschiede beim Zeitpunkt
des Engraftments oder der chronischen GVHD. In der MUD-Gruppe verstarben 3 Patienten
an Komplikationen (DOC) und 2 am Rückfall der Leukämie (DOD), während in der MSD-Gruppe
ein Patient an DOC und 3 an DOD verstarben. 2 der 3 DOC-Patienten aus der MUD-Gruppe
verstarben im Zusammenhang mit einer schweren GVHD, wobei bei einem Patienten wegen
eines Rezidives die Immunsuppression abgesetzt wurde, er eine erneute Remission erreichte
und an den Folgen einer schweren GVHD starb. Das Gesamtüberleben in beiden Gruppen
ist nach 8 und 10 Jahren nach KMT mit 0,5 versus 0,6 vergleichbar. CD25+ T-Lymphozyten spielen sowohl bei der Toleranzinduktion als auch bei der Kontrolle
der Leukämie eine wesentliche Rolle. Die dargestellten Ergebnisse illustrieren die
mögliche Bedeutung der CD25-positiven T-Lymphozyten in der Behandlung der GVHD nach
MUD-Stammzelltransplantation. Weitere Erkenntnisse zum Verständnis der komplexen Rolle
des CD25-Rezeptors auf regulatorischen T-Zellen und Effektor-T-Zellen bei der Erkennung
von Allo-Antigenen und von leukämiespezifischen Antigenen sind notwendig, um die Wirkungen
von CD25-Antikörpern bei Patienten nach MUD-KMT besser zu verstehen und zu bewerten. Da das Gesamtüberleben von Kindern und Jugendlichen mit Leukämie nach MUD-KMT vergleichbar
ist zu Kindern nach MSD-KMT, stellt die HLA-identische, unverwandte Stammzelltransplantation
eine gleichwertige Therapieoption für Kinder mit Hochrisiko-Leukämie und fehlendem
Familienspender dar.
Key words
CD25 - BMT - GVHD - matched unrelated donor - leukemia
Schlüsselwörter
Leukämie - unverwandte Stammzelltransplantation - GVHD - CD25-Antikörper
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A. Wawer
Division of Pediatric Hematology/Oncology and Department of Pediatrics · Munich University
of Technology (TUM)
Kölner Platz 1
80804 München
Germany
Email: angela.wawer@lrz.tum.de