Early responder myeloma: kinetic studies identify a patient subgroup characterized by very poor prognosis.

In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity.

Download Full-text

Coexistent Multiple Myeloma or Increased Bone Marrow Plasma Cells Define Equally High-Risk Populations in Patients With Immunoglobulin Light Chain Amyloidosis

Journal of Clinical Oncology ◽

10.1200/jco.2013.50.8499 ◽

2013 ◽

Vol 31 (34) ◽

pp. 4319-4324 ◽

Cited By ~ 119

Author(s):

Taxiarchis V. Kourelis ◽

Shaji K. Kumar ◽

Morie A. Gertz ◽

Martha Q. Lacy ◽

Francis K. Buadi ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Light Chain ◽

Plasma Cells ◽

Survival Rates ◽

Bone Lesions ◽

Al Amyloidosis ◽

Characteristic Analysis ◽

Bone Marrow Plasma

Purpose There is consensus that patients with light chain (AL) amyloidosis with hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells (CRAB criteria) also have multiple myeloma (MM). The aim of this study was to examine the spectrum of immunoglobulin AL amyloidosis with and without MM, with a goal of defining the optimal bone marrow plasma cell (BMPC) number to qualify as AL amyloidosis with MM. Patients and Methods We identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between January 1, 2000, and December 31, 2010. We defined a population of patients with coexisting MM on the basis of the existence of CRAB criteria (AL-CRAB). Receiver operating characteristic analysis determined the optimal BMPC cut point to predict for 1-year mortality in patients with AL amyloidosis without CRAB to produce two additional groups: AL only (≤ 10% BMPCs) and AL plasma cell MM (AL-PCMM; > 10% BMPCs). Results Among the 1,255 patients, 100 (8%) had AL-CRAB, 476 (38%) had AL-PCMM, and 679 (54%) had AL only. Their respective median overall survival rates were 10.6, 16.2, and 46 months (P < .001). Because the outcomes of AL-CRAB and AL-PCMM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, pooled AL-CRAB and AL-PCMM retained negative prognostic value independent of age, Mayo Clinic AL amyloidosis stage, prior autologous stem-cell transplantation, and difference between the involved and uninvolved free light chain. Conclusion Patients with AL amyloidosis who have more than 10% BMPCs have a poor prognosis, similar to that of patients with AL-CRAB, and should therefore be considered together as AL amyloidosis with MM.

Download Full-text

Multiple myeloma: circulating lymphocytes that express plasma cell antigens

Blood ◽

10.1182/blood.v64.2.352.bloodjournal642352 ◽

1984 ◽

Vol 64 (2) ◽

pp. 352-356

Author(s):

GJ Ruiz-Arguelles ◽

JA Katzmann ◽

PR Greipp ◽

NJ Gonchoroff ◽

JP Garton ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Peripheral Blood ◽

Plasma Cells ◽

Peripheral Blood Lymphocytes ◽

Tumor Burden ◽

B Cell Differentiation ◽

Blood Lymphocytes ◽

Bone Marrow Plasma

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1–3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

Download Full-text

Prognostic value of bone marrow plasma cell infiltration in stage I multiple myeloma

British Journal of Haematology ◽

10.1111/j.1365-2141.1983.tb02851.x ◽

1983 ◽

Vol 55 (4) ◽

pp. 683-690 ◽

Cited By ~ 22

Author(s):

M. Cavo ◽

M. Baccarani ◽

M. Gobbi ◽

A. Lipizer ◽

S. Tura

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Prognostic Value ◽

Stage I ◽

Cell Infiltration ◽

Plasma Cell Infiltration ◽

Bone Marrow Plasma

Download Full-text

The Value of the Bone Marrow Plasma Cell Cytoplasmic Light Chain Ratio in Differentiating Between Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

Leukemia & Lymphoma ◽

10.3109/10428199209051032 ◽

1992 ◽

Vol 8 (6) ◽

pp. 491-493 ◽

Cited By ~ 3

Author(s):

G. Majumdar ◽

R. J. Grace ◽

A. K. Singh ◽

N. G. P. Slater

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Bone Marrow Plasma ◽

Undetermined Significance

Download Full-text

Complement receptors regulate differentiation of bone marrow plasma cell precursors expressing transcription factors Blimp-1 and XBP-1

Journal of Experimental Medicine ◽

10.1084/jem.20042239 ◽

2005 ◽

Vol 201 (6) ◽

pp. 993-1005 ◽

Cited By ~ 57

Author(s):

Dominique Gatto ◽

Thomas Pfister ◽

Andrea Jegerlehner ◽

Stephen W. Martin ◽

Manfred Kopf ◽

...

Keyword(s):

Bone Marrow ◽

B Cells ◽

B Cell ◽

Plasma Cell ◽

Cell Activation ◽

Plasma Cells ◽

Antibody Responses ◽

Complement Receptors ◽

Essentially Normal ◽

Bone Marrow Plasma

Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21–CD19–CD81 coreceptor complex into the B cell antigen receptor (BCR) complex, which lowers the threshold of B cell activation and increases the survival and proliferative capacity of responding B cells. To investigate the role of the CD21–CD35 complement receptors in the generation of B cell memory, we analyzed the response against viral particles derived from the bacteriophage Qβ in mice deficient in CD21–CD35 (Cr2−/−). Despite highly efficient induction of early antibody responses and germinal center (GC) reactions to immunization with Qβ, Cr2−/− mice exhibited impaired antibody persistence paralleled by a strongly reduced development of bone marrow plasma cells. Surprisingly, antigen-specific memory B cells were essentially normal in these mice. In the absence of CD21-mediated costimulation, Qβ-specific post-GC B cells failed to induce the transcriptional regulators Blimp-1 and XBP-1 driving plasma cell differentiation, and the antiapoptotic protein Bcl-2, which resulted in failure to generate the precursor population of long-lived plasma cells residing in the bone marrow. These results suggest that complement receptors maintain antibody responses by delivery of differentiation and survival signals to precursors of bone marrow plasma cells.

Download Full-text