Bone marrow transplantation for Fanconi anemia using low-dose cyclophosphamide/thoracoabdominal irradiation as conditioning regimen: chimerism study by the polymerase chain reaction.
Since 1976, patients grafted at the Hôpital Saint-Louis for Fanconi anemia (FA) without evidence of leukemic transformation have been given a uniform conditioning regimen that consisted of low-dose cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI). The use of low-dose Cy raised the question of whether it is sufficient for the establishment of a complete hematopoietic chimerism in all patients. We therefore initiated a study of chimerism early during hematopoietic reconstitution after bone marrow transplantation (BMT) and thereafter in transplanted FA patients. Minisatellite probes were used after DNA amplification by the polymerase chain reaction (PCR). From July 1989 to October 1992, 24 consecutive patients underwent BMT for FA, 19 of whom were assessable for chimerism. Our results using this sensitive technique showed that, among these 19 patients, all but one successfully engrafted. Engraftment was complete early after BMT in 12. The persistence of a small proportion of recipient's cells was detected in six. This partial hematopoietic chimerism was demonstrated to be only transient in at least five of the six patients. The one patient who failed to engraft showed a recipient-type profile for circulating cells early posttransplantation, indicating autologous bone marrow recovery. A second graft in this patient was also rejected. For both transplantations, the patient was grafted from a matched, unrelated donor. Therefore, 17 of 17 patients successfully grafted and with complete follow up data presented complete hematopoietic chimerism, within the sensitivity limit of the method used. In conclusion, lowering the Cy dose in the conditioning regimen of patients with FA could still allow complete engraftment to occur, at least in patients with an identical sibling donor.
Socié
G
G
Service de Greffe de Moëlle, Hôpital Saint-Louis, Paris, France.
Gluckman
E
E
Raynal
B
B
Petit
T
T
Landman
J
J
Devergie
A
A
Brison
O
O
D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods; D002678:Chimera; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004247:DNA / Q000097:blood*; D005199:Fanconi Anemia / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000503:physiopathology; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D017619:Hemibody Irradiation; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods*
D003520:Cyclophosphamide; D004247:DNA