Recurrent graft failure following syngeneic bone marrow transplantation for aplastic anaemia.
We present the case of a 60-year-old woman with drug-induced aplastic anaemia with a healthy monozygotic twin. Proof of monozygosity was confirmed by studies using the hypervariable minisatellite probe to obtain identical DNA fingerprints in donor and recipient. In vitro co-culture studies performed showed no evidence of a recipient-derived cellular or humoral inhibitor of donor haemopoiesis. Despite this, there was no engraftment following simple marrow infusion without preconditioning. A second syngeneic transplant following high dose cyclophosphamide therapy produced trilineage engraftment but severe thrombocytopenia developed at 3 months, followed later by pancytopenia with generalized marrow failure. Following a third syngeneic transplant with cyclophosphamide and total lymphoid irradiation there was good initial engraftment but graft failure occurred at 14 weeks. A fourth transplant using Campath 1G as preconditioning resulted in no engraftment and the patient died of septicaemia 8 weeks following her fourth transplant. We suggest that the cause of the recurrent aplastic anaemia in this case was a defect of marrow stroma as neither an inhibitor of donor haemopoiesis nor an intrinsic defect of donor stem cell growth could be demonstrated in vitro.
Marsh
J C
JC
Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Harhalakis
N
N
Dowding
C
C
Laffan
M
M
Gordon-Smith
E C
EC
Hows
J M
JM
D000741:Anemia, Aplastic / Q000209:etiology / Q000235:genetics / Q000601:surgery*; D016026:Bone Marrow Transplantation / Q000276:immunology; D004200:Diseases in Twins; D005260:Female; D006084:Graft Rejection; D006801:Humans; D008875:Middle Aged; D012086:Reoperation; D014185:Transplantation, Isogeneic; D014430:Twins, Monozygotic