Anti-factor VIII antibodies of hemophiliac patients are frequently directed towards nonfunctional determinants and do not exhibit isotypic restriction

A significant proportion of hemophilia A patients receiving transfusions of factor VIII (FVIII) develop a specific antibody response towards FVIII. These antibodies are usually detected by assays in which they inhibit the function of the molecule, such as the Bethesda clotting test. We have prepared anti-FVIII antibodies by specific immunoadsorption from the plasma of four hemophiliacs with stable inhibitor levels. The isotypic distribution of such antibodies was determined and their capacity to bind to insolubilized FVIII was compared with their inhibitory activity in two functional assays, namely, the Bethesda assay and a chromogenic assay. In addition, the FVIII epitope specificity was determined by competition with monoclonal antibodies for the binding to insolubilized FVIII. We show here that (1) anti-FVIII antibodies are not isotypically restricted; thus, a significant proportion of specific IgG2 was found; (2) antibodies are frequently directed towards epitopes of FVIII that are not directly involved in the function of the molecule and therefore escape detection in the Bethesda method or chromogenic assay; and (3) each patient shows a unique pattern of FVIII epitope recognition. We conclude that evaluation of anti-FVIII antibodies by a functional method does not provide an accurate evaluation of the specific antibody response. These findings have important implications for the comparison of the immunogenicity of FVIII molecules produced by different technologies and for the development of methods to control anti-FVIII antibody production.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

Amyloidosis of the breast mimicking recurrence in a previously treated early breast cancer

Amyloid involvement of the breast is infrequently reported and may have clinical and radiological features suspicious for a primary breast malignancy. We describe a case of amyloid of the breast in which asymptomatic mammographic findings were suspicious for locally recurrent disease in a patient with previously treated breast cancer.     

Technique for axillary radiotherapy using computer‐assisted planning for high‐risk skin cancer†

High‐risk skin cancer arising on the upper limb or trunk can cause axillary nodal metastases. Previous studies have shown that axillary radiotherapy improves regional control. There is little published work on technique. Technique standardization is important in quality assurance and comparison of results especially for trials. Our technique, planned with CT assistance, is presented. To assess efficacy, an audit of patients treated in our institution over a 15‐month period was conducted. Of 24 patients treated, 13 were treated with radical intent, 11 with this technique. With a follow up of over 2 years, the technique had more than a 90% (10/11) regional control in this radical group. Both of the radical patients who were not treated according to the technique had regional failure. One case of late toxicity was found, of asymptomatic lymphoedema in a radically treated patient. This technique for axillary radiotherapy for regional control of skin cancer is acceptable in terms of disease control and toxicity as validated by audit at 2 years.