IN MULTIPLE-MYELOMA, CLONOTYPIC B-LYMPHOCYTES ARE DETECTABLE AMONG CD19(-BLOOD CELLS EXPRESSING CD38, CD56, AND MONOTYPIC IG LIGHT-CHAIN() PERIPHERAL)

Multiple myeloma (MM) is characterized by a plasma cell infiltrate of the hone marrow (BM). However, late-stage monotypic B cells have been detected in the blood. This work analyzes the effects of clinical trea tment on late stage CD19(+) B cells present in 752 blood samples from 152 MM patients. MM patients have 2 to 8 times as many circulating CD1 9(+) cells as do normal donors. Analysis of the Ig heavy chain (IgH) g ene rearrangements using polymerase chain reaction indicates that the CD19(+) population includes cells sharing the same clonotypic CDR3 reg ion as is detected in the BM plasma cells, for patients analyzed durin g chemotherapy or in relapse. They are also monotypic as defined by th eir cytoplasmic or surface expression of Ig kappa- or lambda light cha in. The light chain restriction is the same as that of the BM plasma c ells. Individual patients observed over 1- to 2-year periods exhibit c onsiderable variation in the number of B cells present in blood; this number does not correlate with the concentration of serum monoclonal I g. The monoclonal blood CD19(+) cells are not eliminated by any of the chemotherapy regimens analyzed and remain at high levels during trans ient remissions. Patients in the progressive phase of disease or in re lapse have significantly higher numbers of B cells than do patients in transient remission or untreated patients. During periods when the qu antity of blood B cells approaches normal, phenotypically their qualit y is highly abnormal, with physical and phenotypic heterogeneity. Most B cells express CD45R0, a high density of CD38, and CD56 characterist ic of late-stage B or pre-plasma cells. CD38(hi) blood B cells had a c yclical presence. We conclude that monoclonal B cells in the blood of myeloma patient populations include drug-resistant reservoirs of clono typic cells that may underlie relapse. (C) 1995 by The American Societ y of Hematology.