Related Plasma Cell Dyscrasias Research Articles

Immunophenotypic characterization of normal and abnormal plasma cells in bone marrow of newly diagnosed multiple myeloma patients

Identification of plasma cells into abnormal (APC) and normal (NPC) compartments is of utmost importance in flow cytometric (FC) analysis of multiple myeloma (MM) and related plasma cell dyscrasias for diagnosis, prognosis, and follow-up. No single phenotypic marker is sufficient to distinguish NPC from APC. 43 newly diagnosed cases of MM and 13 controls were included in the study. Bone marrow (BM) samples from the 2nd pass were processed on the same day with antibodies against CD38, CD138, CD19, CD81, CD45, CD117, CD200, CD56, cytoKappa, and cytoLambda in a 4-color experiment with CD38 and CD138 as gating antibodies. Mean APC% in cases was 96.5%. The expected Immunophenotype (IP) of APC which is CD19-/56+/45-/81-/117+/200+ was found in only 13/43 MM cases. In 30/43 cases, APC revealed deviation from expected IP either for single or a combination of markers. Sensitivity for APC detection was highest for CD19 (95.2%) followed by CD56 (90.4%) and CD81 (83.7%). Specificity was highest for CD19 (100%), CD56 (100%), and CD81 (100%) followed by CD117 (92.3%). Combination of markers with maximum sensitivity to detect APC (97.6%) was CD81- or CD19- and CD200+ or CD56+ (two markers); and for NPC (92.3%) was CD81+ and CD19+ and CD56- (three markers). Plasma cell IP can be highly variable with multiple minor subpopulations in both cases and normal controls. CD 19 and CD56 are highly informative markers for a 4-color experiment. Assessment of multiple markers in an 8-10 color experiment is more informative but the lack of advanced flow cytometers should not limit the use of FC in a 4-color approach. Our results emphasize that even basic equipment with limited fluorochrome can provide meaningful information if used appropriately.

OAB-049: Poor post-vaccination anti-SARS-CoV-2-antibody response in patients with Multiple Myeloma correlates with low CD19+ B-lymphocyte count and anti-CD38 treatment

BackgroundUp to now, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma (MM) and related plasma cell dyscrasias, after the first dose of anti-SARS-CoV-2 vaccination.MethodsIn this single-center study, patients aged 18 years and older with a confirmed diagnosis of MM, monoclonal gammopathies of clinical significance (MGCS) or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations were included. Data were collected between January 1st and May 21th, 2021, at the department of oncology and hematology at the University Medical Center Hamburg-Eppendorf, Germany. The primary aim of this study was to evaluate a possible correlation between antibody titers and CD19+ B lymphocyte count and secondary to identify other possible factors influencing immune response. This study is part of the COVIDOUT trial (NCT04779346). Written informed consent was provided by each patient according to local requirements.ResultsA total of 82 patients were included in this study. The median age was 67.5 years (range 40-85 years). 78 patients had MM, 2 MGCS, and 2 AL. Overall, 63 patients were vaccinated with mRNA-based and 19 with vector-based vaccines, respectively. At the time of vaccination, 69 (84.1%) patients were under current anti-myeloma treatment. In total, 34 (41%) patients received anti-CD38-targeting therapies and 52 (63%) patients received IMiD-based therapies. 57 (69.5%) patients were in deep remissions (very good partial remission or better) at the time of vaccination. Assessment of anti-SARS-CoV-2 spike protein antibody titer (SP-AbT) took place on a median of 25 days after the first vaccination (SD ± 11.8). A positive SP-AbT was detected in 23% (17/74) of assessable patients. A cut-off value of ≥ 30 CD19+ B cells/µl was significantly positively correlating with higher SARS-CoV-2 SP-AbT. Individuals with current anti-CD38-antibody treatment showed lower SP-AbT and the likelihood for positive titer results was significantly lower in patients with current anti-CD38 treatment compared to those without. Treatment with immunomodulatory drugs did not harm the development of antibody titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease (≤ partial remission) were significantly negatively correlated with SARS-CoV-2 SP-AbT.ConclusionBased on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination. Since both low CD19+ B lymphocyte count and CD38-directed therapy negatively impact vaccination response, booster vaccination seems therefore of utter importance.

Outpatient Autologous Stem Cell Transplants for Multiple Myeloma: Analysis of Safety and Outcomes in a Tertiary Care Center

BackgroundAutologous stem cell transplant (ASCT) is the preferred consolidation strategy to treat eligible patients with multiple myeloma (MM) and related plasma cell dyscrasias. Given the increasing volume of patients and longer wait time, outpatient ASCT for MM is the standard of care at the Vancouver General Hospital. Patients and MethodsPatients with MM, POEMS syndrome, and amyloidosis undergoing ASCT were included in this analysis. We analyzed patient characteristics, the number of patients requiring admission, duration of admission, 30-day and 100-day mortality, and overall survival. ResultsBetween January 2007 and June 2016, 724 patients underwent 752 ASCTs. Of these, 702 were first ASCTs, 44 were second, and 6 were third. The median age was 60 years (interquartile range [IQR], 54-65 years). Reasons for ASCTs were MM (96.9%) amyloidosis (2.4%), and POEMS syndrome (0.7%). There were 431 (59.5%) males in this group. The median time from diagnosis to transplant was 5 months. Conditioning was melphalan 200 mg/m2 for 89.6% of the patients. Admission to the inpatient ward was required by 245 (32.6%) patients within the first 30 days. The median time to admission was 9 days post-transplant (IQR, 5-13 days). The median duration of admission was 6 days (IQR, 3-9 days). The day 100 all-cause mortality rate was 0.9%, and transplant-related mortality was 0.4%. ConclusionOutpatient ASCT is a safe and feasible treatment strategy with low transplant-related mortality. Overall resource utilization is significantly lower than inpatient ASCT: however, this requires a multidisciplinary approach with close follow-up.

European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias.

The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease. The management of light chain amyloidosis depends on the presence and severity of heart disfunction. If present, intensification with an autologous stem cell transplantation (ASCT) is not recommended. Further aggregation of misfolded light chains could be prevented by doxycycline or monoclonal antibodies targeting amyloid deposits. Initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens. For relapsing patients, one can consider proteasome inhibitors, immunomodulatory agents, melphalan or daratumumab. Because intact or light-chain immunoglobulins are also the culprits for MIDD, the small monoclonal plasma cells' clones should be treated and generally respond well to bortezomib-based treatment. POEMS syndrome is a well-defined clinical entity that can present as solitary bone lesions or disseminated disease. Radiation therapy is used for patients with localized disease and result in long-lasting response. Systemic treatment should be proposed to patients with disseminated disease, but regimens that can worsen a pre-existing polyneuropathy should be avoided. PPCL is located at the other end of the spectrum of plasma cell disorders and is associated with an aggressive disease course and poor prognosis. It requires an imminent, multi-phase and novel agents-based therapy, including induction, ASCT, consolidation and maintenance, with short treatment-free intervals. Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic stem cell transplantation can be used in selected patients.

Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias.

Monoclonal immunoglobulins are markers of plasma cell proliferative diseases and have been described as the first (and perhaps best) serological tumor marker. The unique structure of each monoclonal protein makes them highly specific for each plasma cell clone. The difficulties of using monoclonal proteins for diagnosing and monitoring multiple myeloma, however, stem from the diverse disease presentations and broad range of serum protein concentrations and molecular weights. Because of these challenges, no single test can confidently diagnose or monitor all patients. Panels of tests have been recommended for sensitivity and efficiency. In this review we discuss the various disease presentations and the use of various tests such as protein electrophoresis and immunofixation electrophoresis as well as immunoglobulin quantitation, free light chain quantitation, and heavy-light chain quantitation by immuno-nephelometry. The choice of tests for inclusion in diagnostic and monitoring panels may need to be tailored to each patient, and examples are provided. The panel currently recommended for diagnostic screening is serum protein electrophoresis, immunofixation electrophoresis, and free light chain quantitation.

A Phase I Trial of Pomalidomide, Bortezomib (Velcade), and Dexamethasone (PVD) As Initial Treatment of AL Amyloidosis and Light Chain Deposition Disease

Introduction: AL amyloidosis (AL) and Light Chain Deposition Disease (LCDD) are plasma cell dyscrasias in which misfolded monoclonal light chains form insoluble extracellular protein deposits (fibrillar and amorphous, respectively). In AL particularly, toxic soluble light chain oligomers also play a role in disease pathogenesis. Treatment of AL and LCDD aims at eliminating the abnormal plasma cell clone. Typical agents used include corticosteroids, bortezomib (btz), alkylators, or immunomodulatory drugs (IMiDs) such as lenalidomide (len) or pomalidomide (pom). Len-btz-dexamethasone (dex) is a highly efficacious frontline regimen commonly used for multiple myeloma, a related plasma cell cancer. Despite this, prospective studies using btz-IMiD combos as initial therapy of AL or LCDD are lacking. Here we report our experience with pom-btz-dex(PVD) for pts with AL or LCDD.Methods: This is a prospective Phase I trial using a standard 3+3 dose escalation scheme (described in Table 1). The primary objective is to establish the maximally tolerated dosing (MTD), with assessment for dose limiting toxicity (DLT) extending through cycles 1 and 2 for each pt. Hematologic and organ responses (HR and OR) were assessed using recently updated guidelines. PVD was administered in repeating 28-day cycles until either DLT or progressive disease. Key inclusion/exclusion criteria: biopsy proven AL amyloidosis or LCDD; no more than 1 prior cycle of anti-plasma cell therapy; measurable disease defined as at least a 5 mg/dL difference between the involved (iFLC) and uninvolved (uFLC) serum free light chains, or a serum M-protein of 0.5 g/dL or greater (latter not permissible without measurable sFLCdifference after protocol amendment); ECOG PS of 2 or less; adequate renal, hepatic, and marrow function; no Grade 3 or higher peripheral neuropathy (PN; pts with painful grade 2 PN also excluded). Abnormal left ventricular ejection fraction or cardiac biomarkers allowed, but pts with NYHA class III/IV congestive heart failure or uncontrolled ventricular arrhythmias were excluded. Antithrombotic/antiviral prophylaxis was required for all pts.Results: Six pts have been enrolled thus far (3 each in cohorts 1 and 2, respectively). Three additional pts have already been identified for cohort 3. Five of 6 pts had AL, and 1 had LCDD. Median age was 65.5 yrs (range 49-74 yrs). 5 pts were female. Mayo cardiac stage I/II/III in 1, 2, and 3 pts, respectively. Three pts had one prior cycle of therapy (the others had none). The iFLC was lambda type in all 5 AL pts, and kappa for the pt with LCDD. Median number of organs involved by AL/LCDD was 2 (range, 2-4; 4 with both cardiac and renal, and 1 additional pt with cardiac). The median number of PVD cycles administered was 3 (range 1-6). Two pts are still on therapy. The reasons for stopping PVD in the other 4 pts were: sudden death due to underlying cardiac AL (during cycle 3 of PVD), pt preference after reaching maximal HR (after cycle 6), lack of HR (after cycle 3), and toxicity (after cycle 4). Baseline dex dose adjustment was required for protocol-specified reasons in all pts. One pt required further dex reduction during cycle 4 of PVD. No pts required baseline or subsequent modification of pom or btz. Table 2 summarizes reported adverse events (AEs). No DLTshave been observed. Two pts achieved HR (0 CR, 1 VGPR, 1 PR, 3 SD, 0 PD). Organ responses have not been observed, but the first protocol-specified OR assessment takes place after 4 cycles of PVD and some pts have yet to reach this time point.Conclusions: PVD was well tolerated in this group of pts with AL and LCDD. Importantly, no significant myelosuppression or PN was noted in the first 2 (out of a planned 4) dose cohorts. Most AEs have been related to the ptsÕ underlying AL/LCDD, though dex has posed difficulties for some pts. Hematologic responses have been seen, but organ responses are predictably lagging. Once the MTD is established, an 18-pt expansion cohort dosed at that level willfurther examine the efficacy of PVD as up-front treatment for AL and LCDD. [Display omitted] DisclosuresZonder:Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Off Label Use: Pomalidomide and Bortezomib are approved drugs for multiple myeloma; they are used in this trial as treatment for the related plasma cell dyscrasias AL amyloidosis and light chain deposition disease. . Tuchman:Celgene: Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Research Funding, Speakers Bureau. Kukreti:Celgene: Honoraria. Burt:Celgene: Speakers Bureau. Matous:Takeda Pharmaceuticals International Co.: Speakers Bureau; Onyx: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Seattle Genetics, Inc.: Research Funding, Speakers Bureau.

Imaging of Multiple Myeloma and Related Plasma Cell Dyscrasias

Multiple myeloma (MM) is an incurable plasma cell malignancy of the bone marrow. MM has 3 components: diffuse marrow infiltration, focal bone lesions, and soft-tissue (extramedullary) disease. The hallmark biomarker in blood or urine is a monoclonal immunoglobulin, the monoclonal protein. Waldenstrom macroglobulinemia is a similar disease with secretion of IgM. Staging is classically performed with the 1975 Durie-Salmon system, which includes conventional radiographs. Recently updated, the Durie-Salmon Plus staging system includes CT, MRI, and (18)F-FDG PET/CT. The hallmark radiographic lesion of symptomatic MM is a well-demarcated, focal osteolytic bone lesion. The number of focal bone lesions correlates inversely with outcome. Extramedullary disease is typically an aggressive, poorly differentiated form of MM that confers inferior outcome, with median survival of less than 1 y if present at diagnosis. Achievement of a complete response on (18)F-FDG PET before stem-cell transplantation correlates with a superior outcome.

An In Vivo Model To Investigate the Nature of the Cell-of-Origin of Multiple Myeloma.

Multiple myeloma (MM) and related plasma cell dyscrasias are characterized by monoclonal expansion of terminally differentiated plasma cells. However, it is puzzling how the quiescent plasma cell can be the source of often aggressive and relapsing neoplasms. We and others have postulated that the myeloma clonogenic progenitor may reside in a more immature compartment with greater self-renewal capacity, most probably a maturing plasmablast precursor in the germinal center. To investigate the nature of cell-of-origin for these diseases and the genetic requirements for pathogenesis, we have created a novel flexible mouse model system that enables the delivery of stochastic, sequential, somatic mutations to precisely defined compartments of the germinal center in secondary lymphoid tissues. To this end, we have used BAC transgenic technology to express distinct types of avian leukosis virus (ALV) receptors, TVA and TVB, in the expanding centroblast of the dark zone and the committed plasmablast of the light zone, respectively. Mammalian tissues are refractory to transduction by retroviruses of the ALV family unless they ectopically express the cognate avian-derived receptors. Thus, the coding sequences for the TVA receptor, fused to a fluorescent protein tag were placed under the control of transcription factor A-myb, expressed in centroblasts of the dark zone. Similarly, sequences encoding a fluorescent-tagged TVB receptor were placed under the control of transcription factor Blimp1, expressed in the earliest committed plasmablasts as well as mature plasma cells. Analysis of the Blimp1: TVB mice showed that expression of the avian retroviral receptor in the hematopoietic system is limited to the light zone of germinal centers, extrafollicular collections of CD138+ cells in the spleen and lymph nodes as well as long-lived bone marrow plasma cells. Analysis of A-myb: TVA transgenic mice demonstrated expression of the fusion receptor to be restricted to B cells in the immunized spleen but not T cells. Both transgenic systems have been crossed into an Ink4a/Arf-deficient background. We have been transducing plasma cell precursors generated in the course of immune responses to T-dependent antigens with retroviral vectors carrying genes important in myelomagenesis, such as cyclin D1 or c-Myc. Animals are being monitored for development of plasma cell dyscrasias by periodical serum protein electrophoresis (SPEP) and other assays.

Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation.

Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL-6 and GM-CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G-banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.

Radioimmunodetection of human myeloma xenografts with a monoclonal antibody directed against a plasma cell specific antigen, HM1.24.

To develop a new immunologic approach to multiple myeloma, the authors generated a monoclonal antibody against a human plasma cell specific antigen, HM1.24. Their previous study showed the antitumor effect of this antibody in severe combined immunodeficiency (SCID) mice bearing human myeloma xenografts. In the current study, the efficacy of anti-HM1.24 immunoglobulin (Ig) G and its F(ab')2 fragment were evaluated for radioimmunologic detection of the myeloma xenografts. SCID mice bearing subcutaneous RPMI 8226 tumors were injected with 125I-labeled antibodies, and radioactivity in the tumor and normal tissues was measured. Radioimmunoscintigraphy and autoradiography were performed to investigate the distribution of the antibodies. In comparative biodistribution studies, the maximum tumor localization index of anti-HMl.24 F(ab')2 fragment was significantly higher than that of anti-HM1.24 IgG. Anti-HM1.24 F(ab')2 consistently had higher tumor-to-tissue ratio than anti-HM1.24 IgG and gave distinct tumor images by radioimmunoscintigraphy. Autoradiographic study showed that anti-HM1.24 F(ab')2 penetrated the tumor mass more uniformly than whole IgG antibody. These results indicate that anti-HM1.24 antibody has the potential to provide a new approach to the immunodetection and immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Interleukin-6 in multiple myeloma and related plasma cell dyscrasias

Since the discovery a decade ago that interleukin-6 is a growth factor for human multiple myeloma (MM) cells, great strides have been made in understanding the relationship of this cytokine to multiple myeloma. A plethora of studies on this topic has confirmed that interleukin-6 is a key growth and survival factor for myeloma cells, as well as a major morbidity factor for patients with MM. Their is strong evidence for both an autocrine (in MM cells) as well as a paracrine sources of interleukin-6 induction (from bone marrow stromal cells and osteoblast cells), with bone marrow stromal cells likely serving as the main center of production of interleukin-6 in patients with MM. Moreover, bone marrow stromal cells from patients with MM express viral interleukin-6, a functional homolog of human interleukin-6 that is produced by Kaposi's sarcoma-associated herpesvirus and may further enhance MM cell growth and survival. Soluble interleukin-6 receptor serum levels are elevated in patients with MM; soluble interleukin-6 receptor may amplify circulating interleukin-6 in patients with MM, and complex with interleukin-6, resulting in proliferation of MM cells that either express low or no detectable surface interleukin-6 receptor. Recent advances in our understanding of interleukin-6 signaling cascades mediating MM growth and survival, as well as its impact on cell cycle regulation in MM cells, may lead to therapeutics designed to interfere with these pathways. Finally, considerable progress has been made in identifying and developing agents including antibodies, biologic agents, hormones and drugs that interfere with the interleukin-6 signaling pathways and may therefore have a role in the treatment of MM.

Immunotherapy of Multiple Myeloma With a Monoclonal Antibody Directed Against a Plasma Cell-Specific Antigen, HM1.24

AbstractMultiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents. Alternative strategies are needed to solve these problems. To develop a new strategy, we have generated a monoclonal antibody (MoAb), which detects a human plasma cell-specific antigen, HM1.24. In this report, we evaluated the in vivo antitumor effect of unconjugated anti-HM1.24 MoAb on human myeloma xenografts implanted into severe combined immunodeficiency (SCID) mice. Two models of disseminated or localized tumors were established in SCID mice by either intravenous or subcutaneous injection of human myeloma cell lines, ARH-77 and RPMI 8226. When mice were treated with a single intraperitoneal injection of anti-HM1.24 MoAb 1 day after tumor inoculation, the development of disseminated myeloma was completely inhibited. In mice bearing advanced tumors, multiple injections of anti-HM1.24 MoAb reduced the tumor size and significantly prolonged survival, including tumor cure, in a dose-dependent manner. The proliferation of cultured human myeloma cells was inhibited in vitro by anti-HM1.24 IgG-mediated complement-dependent cytotoxicity, but not by the antibody alone. Moreover, spleen cells from SCID mice mediated antibody-dependent cell cytotoxicity against RPMI 8226 cells. These results indicate that anti-HM1.24 MoAb can be used for immunotherapy of multiple myeloma and related plasma cell dyscrasias.

A novel membrane antigen selectively expressed on terminally differentiated human B cells

A monoclonal antibody (MoAb) that defines a novel terminal B-cell- restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenstrom's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig- secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non- plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

A Novel Membrane Antigen Selectively Expressed on Terminally Differentiated Human B Cells

A monoclonal antibody (MoAb) that defines a novel terminal B-cell-restricted antigen, termed HM1.24, was developed against a human plasma cell line. The MoAb, designated anti-HM1.24, reacted with five different human myeloma cell lines, as well as with monoclonal neoplastic plasma cells obtained from the bone marrow or peripheral blood of patients with multiple myeloma or Waldenström's macroglobulinemia. The HM1.24 antigen was also expressed by mature Ig-secreting B cells (plasma cells and lymphoplasmacytoid cells) but not by other cells contained in the peripheral blood, bone marrow, liver, spleen, kidney, or heart of normal individuals or patients with non-plasma-cell-related malignancies. The anti-HM1.24 MoAb bound to human myeloma RPMI 8226 cells with an affinity constant of 9.2 x 10(8) M-1, indicating approximately 84,000 sites/cell. By immunoprecipitation assay under reducing conditions, this MoAb identified a membrane glycoprotein that had a molecular weight of 29 to 33 kD. Our studies indicate that the HM1.24-related protein represents a specific marker of late-stage B-cell maturation and potentially serves as a target antigen for the immunotherapy of multiple myeloma and related plasma cell dyscrasias.

Monoclonal plasmacytic ulcerative stomatitis: A plasma cell dyscrasia?

We report a case of extramedullary plasmacytoma that appeared in an uncharacteristic manner as an ulcerative stomatitis affecting particularly the tongue and buccal mucosa. The lesions were associated with a transient lichenoid skin rash. The literature is reviewed and comparisons made between this tumor and the related plasma cell dyscrasias of multiple myeloma and monoclonal gammopathy.

Multiple Myeloma and Related Plasma Cell Dyscrasias

THE PLASMA cell dyscrasias (PCDs), of which multiple myeloma is the most common and also the prototype disease, represent a group of conditions that have as their common feature an abnormal and frequently, but not invariably, neoplastic proliferation of plasma cells.^1-3The term<i>plasma cell</i>is used to describe all cells capable of synthesizing and releasing all classes of immunoglobulins and their subunits, recognizing that this functional definition includes cells with some morphological diversity, variously referred to as "lymphocytoid plasma cells" and "plasmacytoid lymphocytes." As schematically shown in Fig 12-1, the unbalanced or disproportionate proliferation (ie, dyscrasia) of one or a limited number of clones of plasma cells or their B-cell precursors is characteristically associated with the elaboration of excessive quantities of a homogeneous molecular population of one of these proteins, ie, IgG, IgA, IgM, IgD, or IgE, their constituent heavy or light polypeptide components, or both (Fig 12-2).

Multiple myeloma and related plasma cell dyscrasias

Multiple myeloma and related plasma cell dyscrasias