Alaine Wearne

Light chain isotype associated suppression of surface immunoglobulin expression on peripheral blood lymphocytes in myeloma during plateau phase

Summary. Light chain isotype suppression in multiple myeloma has been reported in the plasma cells of the lamina propria of the gut (Leonard et ah 1979). In this paper we present further evidence of systemic suppresssion of the light chain isotype of the paraprotein expressed on normal peripheral blood lymphocytes in myeloma. Twenty patients with myeloma in plateau phase were monitored over 6 months for the expression of either kappa or lambda light chains on the surface of peripheral blood lymphocytes using monoclonal antibodies. The surface markers were analysed on an Ortho Spectrum III flow cytometer. Results of these studies indicate a selective suppression of the cells expressing the light chain isotype of the paraprotein in stable myeloma. Thus, in kappa myeloma there is a low kappa/lambda ratio and in lambda myeloma there is a high kappa/lambda ratio, and this suppression is lost with progressive disease.

Multiple myeloma: the relationship between CALLA (CD10) positive lymphocytes in the peripheral blood and light chain isotype suppression

Summary. This study describes the presence of small numbers of common acute lymphocytic leukaemia antigen (CALLA, CD10)‐positive lymphocytes in the peripheral blood of patients with multiple myeloma. A significant correlation (0.001 < P <0.01) was found between the lack of light chain isotype suppression (LCIS), which is characteristic of progressive myeloma, and the presence of CALLA‐positive lymphocytes. Sixty patients with multiple myeloma, four with benign monoclonal gammopathy (BMG) and seven with solitary plasmacytoma (SP) were monitored in this study. Nineteen of the patients with multiple myeloma demonstrated LCIS, of which only three were found to have CALLA‐positive lymphocytes. Of the 41 patients with multiple myeloma who did not have LCIS, 20 (49%) had CALLA‐bearing lymphocytes. None of the patients with BMG or SP demonstrated LCIS or were found to have CALLA‐bearing lymphocytes in their blood. Forty‐four of the patients with multiple myeloma were also monitored for serum beta‐2‐microglobulin (SB2M levels. There was no correlation between the SB2M and either LCIS or CALLA‐positivity. Detection of CALLA‐positive lymphocytes in the blood of patients with multiple myeloma may be an early marker of the onset of progressive disease. The correlation of CALLA expression on lymphocytes with lack of LCIS provides further evidence for the operation of immunoregulatory systems in these patients.

IMMUNOREGULATION AND PROGNOSIS IN MYELOMA

In patients in the plateau phase of myeloma, expression of the light-chain isotype concordant with the malignant paraprotein on peripheral-blood lymphocytes is suppressed. This light-chain-isotype suppression (LCIS) is lost when the disease becomes progressive. LCIS is identified by quantifying kappa and lambda cells in peripheral blood in an indirect immunofluorescence assay. In 27 patients presenting with myeloma, the prognosis was significantly better for patients with LCIS at presentation than for those without. Bone-marrow mononuclear cells, studied in 7 patients with myeloma and LCIS in peripheral blood, did not show LCIS.

Multiple myeloma: Light chain isotype suppression—A marker of stable disease at presentation

Prognosis in multiple myeloma (MM) is related to the establishment of an immunologically and kinetically characteristic plateau phase. Patients who present with this state may not benefit from immediate chemotherapy. We assessed 20 patients with MM who were staged according to the Salmon and Durie classification at diagnosis and monitored throughout the course of their disease. Patients with a lambda paraprotein and a kappa/lambda lymphocyte ratio in the blood greater than 4.0 were considered to demonstrate light chain isotype suppression (LCIS). Similarly, patients with a kappa paraprotein and a kappa/lambda ratio of less than 0.55 were also considered to have LCIS (1). 14 patients had LCIS; of these, 6 were classified as stage IA, 2 as stage IB, 3 as stage IIA, and 3 as stage IIIA. 6 patients did not have LCIS; 3 were classified as stage IIA, 1 as stage IIIA and 2 as stage IIIB. 10 patients with LCIS were assessed for treatment benefit following administration of melphalan and prednisone, as defined by a fall in the serum paraprotein level of > 50% over 6 months. In 8 patients the serum paraprotein levels did not fall, and the patients remained in good health without clinical deterioration. Thus LCIS at presentation may indicate patients in whom treatment can be safely deferred or in whom aggressive therapy is not indicated.

Automated enumeration of reticulocytes using acridine orange.

&NA; Manual methods of counting reticulocytes using supravital stains, such as new methylene blue, have long been recognized to be subject to technical errors. Automated reticulocyte enumeration has recently become available with the development of an automated cell flow‐cytometer, the Ortho Spectrum III. In this method a fluorescent dye, acridine orange, which stains RNA in a manner similar to supravital stains, is used to distinguish reticulocytes from mature erythrocytes. We have evaluated this technique and found that it compares favourably with manual counting methods.