AMYLOIDOSIS OF THE AL-TYPE - CLINICAL, MORPHOLOGIC AND BIOCHEMICAL ASPECTS OF THE RESPONSE TO THERAPY WITH ALKYLATING-AGENTS AND PREDNISONE

A patient with nephrotic syndrome was found to have amyloid deposition in the kidneys, skin and gastrointestinal tract. His serum and urine contained monoclonal λ light chains. In the serum, the light chains were found as tetramers and dimers, whereas the urinary form was primarily dimer. His marrow contained 16 per cent plasma cells at the time of diagnosis. He was treated with the alkylating agents melphalan and cyclophosphamide plus prednisone. He exhibited remarkable clinical improvement during the period of therapy concomitant with the eventual disappearance of monoclonal light chain production, marked reduction in proteinuria, increased normal serum protein production and documented reduction in tissue amyloid deposition. Biosynthetic studies were carried out with the patient's bone marrow cells obtained before, during and after cytotoxic therapy. Initially, λ-chain tetramers were noted in cytoplasmic extracts and secretions of the marrow cells in short-term tissue culture. Reduction and alkylation of the molecules precipitable with anti-light chain antiserums revealed light chain monomer and a smaller molecule of approximately 10 to 12,000 daltons in size. Experiments carried out after the completion of therapy revealed no detectable excess light chain synthesis. Similar studies in three other patients with AL fibril deposition indicated that all synthesized light chain dimers, but none produced larger polymers either intra- or extracellularly. A smaller molecule was identified in one of the three. These observations support the previously suggested association of the occurrence of high molecular weight light chain polymers in the serum with AL amyloid deposition. In addition, the clinical improvement noted in conjunction with cytotoxic therapy raises the possibility of the existence of subsets of patients with AL deposition who will respond to these agents. © 1979.