The relationship between the anomalous and normal immunoglobulins was studied through measurement of myeloma protein (MP), Bence Jones protein (BJP), and the normal γG, γA, γM and γD-globulin levels in a large group of patients with multiple myeloma. These determinations were made prior to and after initiation of three different therapeutic protocols.

Thirteen out of 18 patients had at least a 25 per cent reduction in MP or BJP within 6 months. This response was characterized by considerable variation both in the rate and period of time before the anomalous proteins decreased. The type of response was independent of (1) light chain type (K or L) of G or A-MP, (2) heavy chain subgroup or genetic (Gm) factors of G-MP, and (3) electrophorectic mobility of the MP. The ratio among multiple components of heterogenous G or A-MP was not altered by therapy. The initial level of MP, in the case of patients with G-MP, may be one factor in the type of response observed.

The rate of reduction of MP and BJP was extremely rapid in patients who received prednisone in conjunction with melphalan. It appeared that synthesis of anomalous γ-globulin components was completely suppressed with this treatment regimen. This type of response was not observed in patients treated with melphalan alone.

The mean values for each of the normal immunoglobulin (IG) classes (γG, γA, γM and γD-globulin) were reduced below normal. Two classes, γA and γD-globulin, were particularly low. Prior to therapy, however, the extent of reduction of each IG class varied in an individual patient. An inverse relationship was found for γM-globulin and G-MP levels. Part of the normal γG-globulin in patients with G-MP was determined by measurement of Vi (γ2c) levels. Different patterns of response to therapy were noted for each class of IG. More commonly, the response of a normal IG was independent of the response of the anomalous protein and furthermore, could not be related to a particular treatment schedule. In some instances, therapy contributed to further suppression of normal IG levels.

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