Re-Transplantation from the Same Unrelated Donor in Three Adolescents with Severe Aplastic Anemia After Graft Rejection

Abstract

Hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD) has become the accepted salvage treatment for patients with severe aplastic anemia (SAA) lacking a matched sibling donor and failing immunosuppressive treatment. However, non-engraftment and early rejection remain main reasons for treatment related morbidity and mortality. We report on three adolescents who were grafted from MUD, rejected their graft and were re-grafted 47–51 days after first HSCT from the same donor. For conditioning, fludarabine, cyclophosphamide, ATG and/or OKT3 in combination with total lymphoid irradiation was used. Unmanipulated peripheral blood stem cells at a minimum dose of 8×10⁶/kg CD34+cells were infused. Acute toxicity was low. Two patients are alive and well for more than 3 years, one patient developed extended chronic graft-versus-host disease from which he died 34 months after second HSCT. Re-transplantation from MUD in the case of non-engraftment or rejection from the same donor is possible following immunoablation combined with intensive serotherapy in young patients with SAA.

Zusammenfassung

Die hämatopoetische Stammzelltransplantation (HSZT) vom unverwandten Spender (MUD) stellt die Salvagetherapie für Patienten mit schwerer aplastischer Anämie (SAA) ohne passenden Geschwisterspender und nach erfolgloser immunsuppressiver Therapie dar. Nonengraftment und frühe Abtoßung sind Hauptursachen für therapieassoziierte Morbidität und Mortalität. Wir berichten über drei Jugendliche mit SAA und HSZT von einem MUD mit nachfolgender Abstoßung, die 47–51 Tage nach erster Transplantation vom gleichen Spender retransplantiert wurden. Die Konditionierung erfolgte mit Fludarabin, Cyclophosphamid, ATG und/oder OKT3 kombiniert mit totaler Lymphknotenbestrahlung. Es wurden unmanipulierte periphere Blutstammzellen (≥8×10⁶/kg CD34+Zellen) transplantiert. Die Akuttoxizität war gering. Zwei Patienten leben mehr als 3 Jahre nach HSZT, ein Patient entwickelte eine chronisch extensive Transplantat-gegen-Wirt-Erkrankung, an der er 34 Monate nach zweiter HSZT verstarb. Eine Re-Transplantation vom gleichen MUD ist bei Nonengraftment bzw. Abstoßung nach Immunoablation in Kombination mit intensiver Serotherapie bei jungen Patienten mit SAA möglich.

Key words

aplastic anemia - stem cell transplantation - graft rejection - matched unrelated donor - adolescent - re-transplantation

Schlüsselwörter

aplastische Anämie - Stammzelltransplantation - Abstoßung - unverwandter Spender - Jugendlicher - Re-Transplantation

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