Highly Sensitized Patients: Miami Transplant Institute Experience.
BACKGROUND
Transplantation continues to be challenging in highly sensitized patients. Herein, we compared induction immunosuppression (IS) based on immunologic risk stratification and desensitization with intravenous immunoglobulin (IVIG).


METHODS
Of the 42 highly sensitized kidney and 3 kidney-pancreas transplant recipients who underwent IVIG for desensitization from 2008-2014, 10 (Control group) received standard induction IS with antithymocyte globulin, basiliximab, and methylprednisolone, and 35 (Rituximab group) received standard IS with rituximab ± IVIG ± plasmapheresis. Immunologic risk stratification was based on donor specific antibodies (DSA), flow crossmatch ratio, and calculated panel reactive antibody. All patients received tacrolimus, mycophenolate, and steroids for maintenance IS. Unacceptable antigen cut-offs for class I and II DSA were 6000 and 9000 mean fluorescence intensity and 2.0 and 4.4 channel shift ratios for T and B cell flow cytometry crossmatch, respectively. All complement dependent cytotoxicity T cell crossmatch negative patients were transplanted.


RESULTS
Characteristics between groups, including high risk level, previous transplantation rate, number of human leukocyte antigen mismatches, delayed graft function rate, rejection rate, serum creatinine, and estimated glomerular filtration rate at 1 year (1.48 ± 0.6 and 50 ± 17 versus 1.1 ± 0.4 mg/dl and 66 25 ml/min) were not statistically significant between the Control and the Rituximab groups, respectively. Waiting time for the Control group was 6.4 years versus 4.1 years for the Rituximab group (p = 0.009). The cumulative proportion of patients who remain free of death or allograft failure was significantly higher in the Rituximab (87%) versus the Control group (60%) (p = 0.047).


CONCLUSIONS
In highly sensitized patients who received desensitization with IVIG, the addition of Rituximab to our standard IS (and/or IVIG and plasmapheresis as per the immunologic risk stratification model) resulted in higher cumulative patient and graft survival.
Adela D
AD
Mattiazzi
Alexandra
A
Centeno
Alexandra
A
Amador
Casiana
C
Fernandez-Bango
Catherine Dillard
CD
Scowby
Marian
M
O'Rourke
Tamieka
T
Hill-Matthie
Ronak
R
Patel
Frances
F
Barrios
Phillip
P
Ruiz
Linda
L
Chen
Junichiro
J
Saghesima
Gaetano
G
Ciancio
George W
GW
Burke
Michael
M
Goldstein
Jayanthi
J
Chandar
Gabriel
G
Contreras
David
D
Roth
Warren
W
Kupin
Giselle
G
Guerra
Rodrigo
R
Vianna
D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D005431:Florida; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000401:mortality; D010956:Plasmapheresis; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab