Donor-HLA-incompatible marrow transplantation with an anti-donor cytotoxic antibody in the serum of the patient.
A 42-year-old female with acute mixed lineage leukemia received a marrow transplantation from an HLA non-identical sibling. The serum of the patient showed a positive crossmatch for anti-donor lymphocytotoxic antibody and exhibited a complement-mediated cytotoxicity to donor hematopoietic progenitor cells. In an attempt to reduce the risk of graft rejection, a large volume plasma exchange was performed, which was followed by an infusion of irradiated donor lymphocytes to eliminate remaining antibodies from her serum. The level of anti-donor antibody fell below the sensitivity of the anti-human immunoglobulin lymphocytotoxicity test after the infusion of donor lymphocytes. The cytotoxic activity against donor progenitor cells also disappeared from the serum. Cyclosporin had been administered for 2 weeks before marrow infusion, and methylprednisolone and prednisolone for 1 week before the initiation of conditioning chemoradiotherapy. Conditioning comprised cytosine arabinoside 5.6 g/m2, cyclophosphamide 4500 mg/m2 and fractionated total body irradiation with 15 Gy followed by an infusion of 4.0 x 10(8) cells/kg of unmodified marrow cells. Engraftment of donor cells was documented by HLA typing of peripheral lymphocytes. A sustained engraftment may be obtained in a donor-incompatible HLA non-identical marrow transplantation with anti-donor antibody by elimination of the antibody and achieving an intensive immunosuppression in the recipient before marrow infusion.
Maruta
A
A
Department of Hematology-Chemotherapy, Kanagawa Cancer Center, Japan.
Fukawa
H
H
Kanamori
H
H
Harano
H
H
Noguchi
T
T
Kodama
F
F
Kase
N
N
Matsuzaki
M
M
Miyashita
H
H
Motomura
S
S
D000328:Adult; D000906:Antibodies / Q000032:analysis / Q000502:physiology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D006680:HLA Antigens