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1.
Br J Haematol ; 189(3): 551-558, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32086819

RESUMO

Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo-immunization resulting in platelet transfusion refractoriness and a high risk for life-threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo-antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo-immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10-60 min and 18-24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post-transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA-incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo-immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos HLA/imunologia , Imunização/métodos , Transfusão de Plaquetas/métodos , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
3.
Cancer Lett ; 216(2): 227-41, 2004 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-15533599

RESUMO

The cancer recognition (CARE) antibody (Ab) test is a serologic assay for a specific IgM that is elevated in cancer patients. All tests are measured using an indirect enzyme-linked immunosorbent assay (ELISA) of human serum. The target polypeptide in the CARE Ab test is the IgM binding epitope (LT-11) of the CARE antigen (Ag) consisting of a 16 mer structure that has been produced synthetically. The mean relative concentration (MRC) is determined relative to standard, normalized human plasma. Non-parametric analysis showed median MRC values of healthy volunteers (HVs) with no history of cancer (n =47), family history of cancer (n = 126) and a previous cancer history (n = 24) to be 26, 34 and 46, respectively. It was determined that there was no significance found among the medians of the three HV groups (P = 0.53). The specificity of the HV types was between 87 and 98%. Benign/non-cancer surgical patients (n = 27) had a median value of 20 with a specificity of 96%. The cancer patients (n = 61) had a median value of 246 with a sensitivity of 89%. There was a significant difference between the HV and cancer patients (P < 0.0001) as well as between the benign/surgical non-cancerous group and cancer patients (P < 0.0001). The IgM antibody is heat stable at room temperature for two days versus being frozen at -80 degrees C (r2 = 0.97). Either serum or plasma samples may be used in the CARE Ab test (r2 = 0.92). The CARE Ab was almost exclusively IgM with no serum conversion to IgG in sequential measurements of patients with cancer over a six-month period. Preliminary data from patients undergoing post-operative cancer treatment showed that decreasing Ab levels revealed patients negative for residual cancer or undergoing remission, while relapsing patients show an increase in Ab levels. A return to a positive Ab level shortly after treatment is a poor prognostic sign while in advanced cancers the Ab levels may be depressed significantly.


Assuntos
Anticorpos Antineoplásicos/sangue , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/sangue , Epitopos Imunodominantes/imunologia , Neoplasias/diagnóstico , Testes Sorológicos/métodos , Estudos de Casos e Controles , Linhagem Celular Tumoral/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina M/sangue , Estadiamento de Neoplasias , Neoplasias/sangue , Neoplasias/imunologia , Prognóstico , Sensibilidade e Especificidade
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