Use of intravenous immune globulin and rituximab for desensitization of highly HLA-sensitized patients awaiting kidney transplantation.
BACKGROUND.: We have shown that high-dose intravenous immune globulin (IVIG; 2 g/kg x2 doses)+rituximab (1 g x2 doses) was effective in lowering anti-human leukocyte antigen (HLA) antibodies and improving rates of transplantation. The aim of this report was to evaluate the efficacy of IVIG+rituximab on reduction of anti-HLA antibodies to a level that was permissive for living donor (LD) or deceased donor (DD) transplantation without incurring the risk of antibody-mediated rejection and immediate graft loss. METHODS.: From July 2006 to February 2009, 76 HLA-sensitized (HS) patients who met strict sensitization criteria received kidney transplants after desensitization using IVIG 2 g/kg (days 1 and 30)+rituximab (1 g, day 15). Parameters evaluated included rates of transplantation, previous transplants, panel reactive antibodies, donor specific antibody, crossmatches (CMXs), patient and graft survival, acute rejection, serum creatinines, and infections. RESULTS.: Seventy-six HS CMX treated patients (31 LD/45 DD) were transplanted. For LD and DD recipients, significant reductions were seen in T-cell flow cytometry CMXs from pretreatment (T cell 183.5+/-98.4 mean channel shifts (MCS) for LD and 162.8+/-41 MCS for DD) to time of transplant (T cell 68.2+/-58 MCS for LD [P<0.00006] and 125+/-49 for DD [P=0.05]), respectively. Time on wait list for DD recipients was reduced from 95+/-46 months to 4.2+/-4.5 months after treatment. Twenty-eight patients (37%) experienced acute rejection (29% C4d/8% C4d). Patient and graft survival up to 24 months was 95% and 84%, respectively. The mean serum creatinines, at 12 and 24 months were 1.5+/-1.1 and 1.3+/-0.3 mg/dL, respectively. Viral infections were seen in six patients. CONCLUSIONS.: IVIG and rituximab seems to offer significant benefits in reduction of anti-HLA antibodies allowing improved rates of transplantation for HS patients, especially those awaiting DD, with acceptable antibody-mediated rejection and survival rates at 24 months.
Vo
Ashley A
AA
Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Ashley.Vo@cshs.org
Peng
Alice
A
Toyoda
Mieko
M
Kahwaji
Joseph
J
Cao
Kai
K
Lai
Chih-Hung
CH
Reinsmoen
Nancy L
NL
Villicana
Rafael
R
Jordan
Stanley C
SC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D000077562:Valganciclovir; D014777:Virus Diseases / Q000188:drug therapy / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D001323:Autoantibodies; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab; D000077562:Valganciclovir; D015774:Ganciclovir