Dangerous small B-cell clones

Abstract

The detection of a monoclonal immunoglobulin in serum or urine usually raises concerns about the size of the underlying B-cell-derived clone and possible systemic effects caused by its expansion. However, a small clone can synthesize a very toxic protein, producing devastating systemic damage and protean clinical presentations. The resulting "monoclonal componentrelated diseases," although difficult to diagnose, may be progressive and even fatal. The monoclonal protein can aggregate and deposit systemically as occurs in light-chain amyloidosis, monoclonal immunoglobulin deposition disease, crystal-storing histiocytosis, and monoclonal cryoglobulinemia. Alternatively, some monoclonal proteins possess antibody activity toward autogenous antigens and cause chronic cold agglutinin disease, mixed cryoglobulinemia, and peripheral neuropathies. Other humoral mediators may contribute to neuropathy in variant disorders such as the POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. The clone synthesizing the noxious monoclonal proteins is often small, and sensitive techniques may be required to detect these immunoglobulins. A delay in diagnosis can allow irreversible organ damage and dramatically shorten survival. Prompt recognition of suggestive signs and symptoms should trigger a thorough diagnostic approach to reach the correct diagnosis quickly, because this is the key to effective therapy. Although the treatment of these conditions is not optimal, significant advances have been made, improving the duration and quality of life.

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

“…1 The natural history of this disease is primarily determined by the severity of cardiac dysfunction. 2 Patients who present with advanced heart involvement, defined by very high levels of the cardiac biomarker N-terminal pro-natriuretic peptide type-B (NT-proBNP), survive only a few months and represent the most difficult challenge for treating physicians.…”

Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide

“…In primary (AL) amyloidosis, not only is survival dependent on the presence of cardiac involvement but heart dysfunction also limits the feasibility of intensive and effective therapy [1]. The advent of dexamethasone-based regimens, particularly the combinations with melphalan (M-Dex) [2,3] and with cyclophosphamide and thalidomide (CTD) [4], offered patients with advanced disease effective and less toxic alternatives to autologous stem cell transplantation (ASCT).…”

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

“…However, the notion that a malignancy, such as MM or lymphoma, is necessary for the development of kidney disease is no longer valid. Many kidney lesions are, in fact, associated with low-grade plasma cell dyscrasia or lymphoproliferative disorders rather than their malignant counterpart (2). In a large study of patients with Ig light-chain (AL) amyloidosis, 40% were found to have .10% plasma cells in the marrow, but only 8% had evidence of MM (3).…”