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PubMed1993

[Neurologic complications induced by the treatment of the acute renal allograft rejection with the monoclonal antibody OKT3].

The treatment of the acute renal allograft rejection with the monoclonal antibody orthoclone OKT3 produces both systemic and neurologic alterations. In a series of 21 patients with an acute renal allograft rejection treated with this monoclonal antibody, 20 with a renal allograft transplantation and one with a renal and pancreatic allograft transplantation, 29% referred headache associated with fever and vomiting, and 14.2% presented severe neurological alterations induced by the treatment. We stress the need to know these secondary effects to differentiate them from other central nervous system disorders, particularly those of infectious origin.

Adolescent↗
PubMedDate not supplied

HLA-DR incompatibility predicts heart transplant rejection independent of immunosuppressive prophylaxis.

To determine whether immunosuppressive prophylaxis reduces the effect of HLA-DR incompatibility on rejection, we compared clinical and immunologic variables of patients given horse antithymocyte globulin, OKT3, or no immunosuppressive prophylaxis. Median follow-up was 27 months. Groups were similar in race; preoperative HLA reactivity; ABO matching; number of HLA-A, -B, -C, and -DR mismatches; and rejection severity. Patients given immunosuppressive prophylaxis were younger (p = 0.04), had a greater frequency of preoperative ischemic disease (p = 0.03), and had a higher 6-month rejection rate (p = 0.02). A highly significant association was found between the number of mismatches at the HLA-DR locus and rejection severity (p = 0.005). Within the OKT3-based immunosuppressive prophylaxis group and the no immunosuppressive prophylaxis group a significant association was found between the number of HLA-DR mismatches and rejection severity (p = 0.01 and p = 0.009, respectively). A similar trend was identified in the group given horse antithymocyte globulin-based immunosuppressive prophylaxis. Logistic regression, used to identify independent predictors of rejection, showed that the number of HLA-DR mismatches and not the use or type of immunosuppressive prophylaxis is significantly associated with rejection (p = 0.0009). One-year patient survival was 83% in the group with two HLA-DR mismatches and 85% in the group with one or no HLA-DR mismatch. Thus the lower rejection rates in patients with one or no HLA-DR mismatch were not associated with a 1-year survival, which was better than that of patients with two HLA-DR mismatches. The potential benefit of HLA-DR matching on rejection and patient survival must be confirmed by larger prospective studies.

Adolescent↗
PubMedDate not supplied

Triple-drug immunosuppression for heart transplantation in infants and children.

Triple-drug immunosuppression with OKT3 induction is effective rejection prophylaxis in pediatric cardiac allograft recipients. The concerns regarding prevalent lymphoproliferative disease, growth retardation, cytomegalovirus, and other opportunistic infections have not been realized. Since June 1986, 34 pediatric patients, 23 males and 11 females, (age 4 days to 15 years) have undergone orthotopic heart transplantation at our institution. Fifteen patients were less than 6 months old and 13 had type I or II hypoplastic left heart syndrome. There have been four (12%) operative and four (12%) late deaths and a survival rate of 76% after a mean follow-up of 33 months (range, 1 to 82 months). The only deaths attributed to allograft rejection occurred in two newborn recipients (2 and 10 months after surgery) who neither received maintenance steroids nor underwent routine biopsy. The only death from infection (pneumococcus) occurred 6 months after surgery in a 4-year-old patient who was not known to be asplenic. Of the 27 long-term (> 1 year) survivors, 17 (68%) had an average of two rejection episodes during the follow-up period, 10 patients (32%) have been free of graft rejection, and 26 patients (96%) have not experienced a cytomegalovirus infection despite OKT3 induction therapy. Two patients developed lymphoproliferative disease, one of whom was successfully treated by transient reduction of immunosuppression. The other patient died 13 months after transplantation of a lymphoma of the central nervous system. All survivors have demonstrated satisfactory increases in mean height and weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Prophylaxis of heart transplant rejection with either antithymocyte globulin-, Minnesota antilymphocyte globulin-, or an OKT3-based protocol.

We compared an equine antithymocyte globulin (ATGAM)-based protocol with a Minnesota antilymphocyte globulin (MALG)-based protocol and a murine monoclonal CD-3 (OKT-)-based protocol in 3 groups of heart transplant (HT) recipients. Thirty-four recipients received a four-day course of ATGAM. Thirty HT recipients received a 14-day course of OKT3. Fifteen HT recipients received MALG for an average of 10 days. The ATGAM group received cyclosporine beginning preoperatively, while the OKT3 and MALG groups received CyA beginning on post-transplant day 4. All three groups received identical azathioprine and similar steroid therapy. The 3 groups were similar in age, donor/recipient HLA mismatches, and donor/recipient gender mismatches. The MALG and OKT3 groups had 20% and 17% females, respectively, while the ATG group had 41% (p < 0.05). Average follow-up exceeded 14 months for each group. The ATGAM group received a higher dose of CyA during "induction" therapy than the OKT3 and MALG groups, and experienced a greater rise in post-transplant serum creatinine levels. We found no difference between the 3 groups in: preoperative creatinine levels, one-year post-transplant creatinine levels, number of patients who could be successfully "weaned" from steroids, or one-year survival. Other data are tabulated as episodes/patient: [table: see text] We conclude that ATG plus preoperative CyA is superior for rejection prophylaxis following heart transplantation when compared with either MALG plus postoperative CyA or OKT3 plus postoperative CyA.

Analysis of Variance↗
PubMedDate not supplied

Murine monoclonal CD3 antibody (OKT3)-based early rejection prophylaxis in pediatric heart transplantation.

The purpose of this study was to review our experience with the use of OKT3 (a murine monoclonal CD3 antibody) used as immune prophylaxis for pediatric heart transplant recipients. Orthotopic heart transplantation was performed in 18 pediatric patients, 8 girls and 10 boys, ranging in age from 17 days to 17 years. OKT3 therapy was initiated intraoperatively at a dose of approximately 0.2 mg/kg and was administered at a dose of approximately 0.1 to 0.2 mg/kg/day for a period of 11.5 +/- 2.5 days. Daily average OKT3 levels were 1132 +/- 469 ng/ml. Side effects that occurred during OKT3 therapy were fever (59%), diarrhea (24%), headaches (24%), vomiting (18%), encephalopathy (12%), pulmonary edema (6%), and rash (6%). Infections occurred in 24% of patients, all within 6 months of transplantation. In the first year after transplantation, patients experienced 3.4 +/- 2.4 episodes of mild rejection and 1.0 +/- 0.8 episodes of moderate rejection. No patient experienced severe rejection. Five of the surviving 14 patients (36%) have been weaned from chronic steroid therapy, and 42% are being maintained on alternate-day prednisone at a dose of 0.06 +/- 0.02 mg/kg/day. Coronary artery disease developed in three patients; two of whom died. Actuarial survival was 83% at 1 year and 73% at 2 years. This report shows that OKT3 prophylaxis in pediatric heart transplantation can be used with acceptable short-term adverse side effects and overall survival.

Adolescent↗
PubMedDate not supplied

Rapid growth of cutaneous neuroendocrine (Merkel cell) carcinoma during treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.

OKT3 monoclonal antibody has proved to be a potent immunosuppressive agent in treating refractory heart allograft rejections. Recently, however, an increased incidence of lymphoproliferative disorders after OKT3 therapy has been found. This short report describes the rapid growth of a cutaneous neuroendocrine (Merkel Cell) carcinoma, a rare tumor of the dermis promoted by OKT3 administration. Because OKT3 therapy seems to be associated with an increased incidence of neoplasms, frequent patient follow-up is essential.

Carcinoma, Merkel Cell↗
PubMed1993

Preclinical studies for adoptive immunotherapy in bone marrow transplantation. Generation of anti-CD3 activated cytotoxic T cells from normal donors and autologous bone marrow transplant candidates.

In order to obtain T cells for adoptive immunotherapy after autologous bone marrow transplantation (ABMT) for patients with resistant hematological malignancies, a culture system was developed for growing T cells and inducing non-MHC-restricted cytotoxicity using anti-CD3 monoclonal antibody (OKT3) activation. In this investigation, we show that (1) peripheral blood lymphocytes or bone marrow mononuclear cells (BMMNC) from normal donors and cancer patients can be activated with OKT3 and grown in interleukin-2; (2) normal BMMNC activated with OKT3/IL-2 exhibited non-MHC-restricted cytotoxicity and surface markers comparable to that exhibited by normal PBL activated with OKT3/IL-2; (3) both proliferation and cytotoxic functions were IL-2-dependent; (4) PBL activated with OKT3/IL-2 after cryogenic storage grew and killed comparable to PBL activated with OKT3/IL-2 prior to cryopreservation; (5) OKT3/IL-2-activated PBL and BMMNC obtained from 5 patients with non-Hodgkin's lymphomas (NHL) and 1 patient with acute myelogenous leukemia (AML) increased cell numbers 41-75-fold in 2 weeks of culture; 5 of 6 patients with NHL or AML had PBL and BMMNC that exhibited cytotoxic activity; and (6) contaminating leukemic cells did not overgrow in OKT3/IL-2-activated cultures and could no longer be detected on cytospin specimens after 3 weeks of culture. These data show that T cells in PBL or BMMNC from ABMT candidates can be activated with OKT3/IL-2 for adoptive immunotherapy in combination with ABMT.

Antibodies↗