Immunologic reconstitution after haploidentical bone marrow transplantation for immune deficiency disorders: treatment of bone marrow cells with monoclonal antibody CT-2 and complement.
Patients with congenital T lymphocyte deficiency disorders received transplants with parental bone marrow depleted of mature T cells by the use of an anti-T cell monoclonal antibody (CT-2) and complement. Our results with 16 consecutive patients (20 transplants) showed rapid engraftment of donor cells; cytoreduction (busulfan, cytosine arabinoside [ara-C], cyclophosphamide) was used in six transplants, and marrow ablation was used in six (ara-C, cyclophosphamide, 1,365-cGy total body irradiation). No patient received prophylactic anti-graft-v-host disease (GVHD) therapy posttransplant, and only one patient developed significant GVHD, which involved the skin, liver, and gastrointestinal tract. Seven others showed some manifestations of GVHD, but these were of minimal clinical significance and required only occasional steroid therapy. Overall, eight patients are alive and well; eight did not survive. Polyclonal immunoglobulin synthesis by donor memory B cells was seen shortly after transplantation, with peak donor-derived serum levels seen approximately 2 months after transplantation. After this initial immunoglobulin synthesis waned, another wave of B cell responses developed. This immunoglobulin response appears to be permanent. T cell functions appeared as soon as 3 weeks after transplantation. This experience in a variety of patients with combined immunodeficiency who received transplants with monoclonal antibody T cell-depleted marrow shows gratifying results with a consistent T and B cell benefit.
Moen
R C
RC
Horowitz
S D
SD
Sondel
P M
PM
Borcherding
W R
WR
Trigg
M E
ME
Billing
R
R
Hong
R
R
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000473:pathology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002648:Child; D003165:Complement System Proteins / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000209:etiology; D006238:Haploidy; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000628:therapy*; D007167:Immunotherapy / Q000009:adverse effects; D008875:Middle Aged; D013601:T-Lymphocytes / Q000473:pathology
D000911:Antibodies, Monoclonal; D003165:Complement System Proteins