scholarly journals Case report of acquired hemophagocytic lymphohistiocytosis associated with progression of monoclonal gammopathy of unknown significance (MGUS)

2018 ◽  
Vol 5 (1) ◽  
pp. 19
Author(s):  
Li Liu ◽  
Lydia C Contis ◽  
Octavia Melvina Palmer
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
Patient Treatment ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Unknown Significance ◽  
Novel Association ◽  
Prompt Diagnosis

Background: Acquired hemophagocytic lymphohistiocytosis (HLH) is an aggressive hyperinflammatory syndrome. Without prompt diagnosis and proper treatment, it can be life-threatening. HLH is commonly present in the setting of other autoimmune disorders, infection, organ transplantation, and malignancy.  However, to our knowledge, HLH associated with monoclonal gammopathy of undetermined significance (MGUS) has not been reported.Case presentation: A 67-year-old woman with an extensive history of MGUS and renal transplant presented with progressive fatigue, weight loss, intermittent fevers, splenomegaly, and pancytopenia. Serum protein electrophoresis with immunofixation identified a new monoclonal protein IgG lambda and a rapidly increasing pre-existing free kappa light chain. A bone marrow biopsy revealed focal clusters of kappa restricted plasma cells which comprised less than 10\% of marrow cellularity. Skeletal survey was negative for osteolytic lesions. She was also free of any end-organ damage.  Histological examination showed a prominent increase in histiocytes and macrophages, many of which show erythrophagocytosis and lymphophagocytosis. Together with her clinical presentation along with a hyperferritinemia, a diagnosis of HLH was confirmed utilizing the criteria of the Histiocyte Society. The patient underwent a splenectomy. Prompt treatment with etoposide and high dose dexamethasone eventually stabilized the patient and resulted in a full recovery, which coincided with the disappearance of the serum monoclonal IgG lambda.Conclusions: This report reveals a novel association of HLH with the progression of MGUS. Familiarity with this syndrome and its association with other conditions is indicated to ensure prompt diagnosis and appropriate patient treatment.

Phenotypic Analysis of Plasma Cells in Monoclonal Gammopathy and Multiple Myeloma Subjects.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4755-4755
Author(s):  
Lucie Kovarova ◽  
Ivana Buresova ◽  
Ludek Pour ◽  
Renata Suska ◽  
Zdenek Adam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Concentration Level ◽  
Newly Diagnosed ◽  
Phenotypic Analysis ◽  
Benign Monoclonal Gammopathy ◽  
Unknown Significance ◽  
Population Ratio

Abstract Introduction: Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells (PCs). MM and benign monoclonal gammopathy of unknown significance (MGUS) are routinely distinguished on the basis of paraprotein concentration, level of PCs infiltration and the presence or absence of other clinical features. Flowcytometric detection of PCs according to the expression of CD38 and CD138 has limitation in discrimination between normal and abnormal PCs, but this is possible in multicolor phenotypic analysis. The aim of this study is to compare the numbers of normal and abnormal PCs in MGUS and MM subjects and to find some parameter useful for evaluation PCs distribution. Materials and methods: 51 newly diagnosed untreated MM patients (63,9±10,0 years old) and 31 non-treated MGUS subjects (64,2±13,8 years old) were analysed. Lysed whole bone marrows were analysed by flowcytometric immunophenotyping and PCs were indentified by expression of CD38, CD138, CD45 and also CD56 and CD19. Results: Discrimination between normal CD19+ PCs and abnormal CD56+ PCs was done on CD38+CD138+ population. Ratio of normal PCs count and abnormal PCs counts (normal/abnormal=N/A) was used to describe a distribution of PCs. Subjects with MGUS had 0,97±1,65% (average±SD) of CD38+CD138+ cells (median 0,45; range 0,03–7,47%) with average N/A ratio 2,91±3,94 (median 1,36; range 0,01–18,44). Newly diagnosed MM patients had 4,96±9,94% of CD38+CD138+ cells (median 0,85; range 0,02–41,80%) with average N/A ratio 1,70±3,03 (median 0,13; range 0–11,5). In 9,7% MGUS subjects evaluation of distibution of PCs showed transformation of MGUS into MM. In some newly diagnosed MM patients (31,4%) CD38+CD138+ plasma cells were positive for CD19 although they were aberrant and these PCs were mostly CD45+. In some patients (9,7% of MGUS; 17,6% of MM) PC did express neither CD19 nor CD56 and this fact may complicate further evaluation of PCs. Conclusions: Results confirmed that in MGUS subjects we can find lower numbers of PCs which are mostly CD45+CD19+. A majority of plasma cells in newly diagnosed MM patients are abnormal CD56+ PCs and these plasma cells are usually CD45−. Further follow-up of patients can confirm the N/A ratio as a predictive factor for transformation of MGUS into MM and its value for evidence of relapse or progression to active myeloma.

scholarly journals Follow-up Care of Monoclonal Gammopathy of Undetermined Significance: A Guide for Primary Care Physicians

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Hammad Z ◽  
◽  
Hernandez E ◽  
Tate S ◽  
◽  
...  
Keyword(s):  
Plasma Cell ◽  
Primary Care Physicians ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
M Protein ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
End Organ Damage ◽  
Undetermined Significance

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a condition in which M protein, an abnormal monoclonal immunoglobulin, is present in the blood at a nonmalignant level. Specifically, it is defined by: blood serum M protein concentration <3 g/dL (<30 g/L), <10% plasma cells in the bone marrow, and no evidence of end organ damage [1,2]. Evidence of end organ damage includes hypercalcemia, renal insufficiency, anemia, and bone lesions. These are indicative of MGUS progression and which can be attributed to the monoclonal plasma cell proliferative process [3]. MGUS occurs in 3% of the general population older than 50 years. Incidence increases with age and varies with sex with higher rates observered in males than females [1,4]. MGUS is the most common plasma cell disorder, with 60% of patients that present to the Mayo Clinic with a monoclonal gammopathy being diagnosed with MGUS [3]. While it is typically an asymptomatic condition, it is premalignant disorder to other monoclonal gammopathies. Multiple Myeloma (MM) is almost always preceded by MGUS and the majority of patients will have detectable levels of M protein for at least 5 years prior to MM diagnosis [5,6]. MGUS also precedes immunoglobulin light chain (AL) amyloidosis and Waldenstrom Macroglobulinemia (WM) and tends to progress to disorders at a fixed but unrelenting rate of 1% per year [4].

Gene expression profiling (GEP) of cd 138-purified plasma cells (pc) in previously treated multiple myeloma (PTMM): Validating prognostic models developed in newly diagnosed MM (NDMM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8598-8598
Author(s):  
Y. Alsayed ◽  
J. Haessler ◽  
B. Barlogie ◽  
J. Crowley ◽  
J. Shaughnessy
Keyword(s):  
High Risk ◽  
Plasma Cells ◽  
Clonal Evolution ◽  
Single Agent ◽  
Treatment Strategies ◽  
Prognostic Models ◽  
High Dose ◽  
Molecular Subgroup ◽  
Chromosome 1Q ◽  
High Dose Dexamethasone

8598 Background: We have previously reported on the strong discriminatory power in NDMM of GEP-derived 70-gene risk in CD138-purified plasma-cells developed in 351 patients enrolled in TT2 and validated in 441 patients enrolled in two TT3 trials and in PTMM treated with single agent high-dose dexamethasone or bortezomib. Here we report on the overall survival outcomes in 137 patients with PTMM. Methods: Treatment regimens included further autotransplantation and novel agent combinations. The purpose of the investigation was to determine whether PTMM OS was also governed by GEP features, such as high-risk (HR) score, proliferation score (PS), proliferation (PR) molecular subgroup, gain/amplification of chromosome 1q (amp1q) and deletion of the short arm (del1p) and TP53 deletion. Results: Compared with NDMM, PTMM was characterized by greater proportions with HR (32% v 16%, p<0.001), PS (20% v 10%, p=0.002) and PR (24% v 11%, p < 0.001); no difference was observed for TP53 deletion (21% v 30%, p=0.11); amp1q/del1p was more common in PTMM (17% v 9%, p=0.01). OS was 60% at 8yr in NDMM compared to a median of only 2.4yr in PTMM. According to HR, 4-yr OS estimates were 80% for LR v 37% for HR in NDMM (p<0.0001) and 52% for LR v 24% for HR in PTMM (p<0.01). On multivariate analysis of both standard prognostic factors and GEP HR, OS in PTMM was adversely affected by HR status (HR=2.00, p=0.047) and albumin <3.5g/dL (HR=2.66, P=0.013), accounting for a cumulative R2 value of 20%. Conclusions: GEP-derived high-risk features are more prevalent in PTMM relative to NDMM in terms of HR, PS, PR and amp1q/del1p status. As in NDMM, HR status confers poor OS in PTMM. Consistent with serial sampling where LR to HR transformation routinely occurs, these data support the concept that HR in PTMM is derived from clonal evolution. Treatment strategies that presume the existence of underlying HR cells even in LR disease, should be pursued. [Table: see text]

Phase II Trial of Bevacizumab Combined with Low Dose Dexamethasone and Lenalidomide (BEV/REV/DEX) for Relapsed or Refractory Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1173-1173 ◽  
Author(s):  
Martha Raschko ◽  
Stephanie Markovina ◽  
Shigeki Miyamoto ◽  
Walter Longo ◽  
Eliot Williams ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Low Dose ◽  
Plasma Cells ◽  
Response Rate ◽  
Myeloma Cell ◽  
Median Number ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Grade 3

Abstract The interaction between malignant plasma cells and non malignant bone marrow microenvironment has been recognized as both an important feature of MM propagation and a therapeutic target. One critical interaction appears to involve angiogenesis as evidenced by increased blood vessel density in areas of myeloma cell proliferation. The potent anti MM compound lenalidomide may work partly through down regulation of VEGF expression by bone marrow stromal cells. We hypothesized that the addition of the VEGF-A receptor inhibitor, bevacizumab, in combination with low dose weekly dexamethasone, would provide more complete blockade of VEGF activation and translate to increased activity in MM patients with relapsed or refractory disease. ELIGIBILTY: relapsed or refractory MM patients (pts), failing >1 therapy, with no previous exposure to lenalidomide, measurable M protein in serum and/or urine, no current history of unstable cardiovascular disease or uncontrolled thrombosis, no therapy for ≥28 days, and no contraindication to aspirin. METHODS: Each 4 week cycle consisted of lenalidomide 25 mg PO d1–21, bevacizumab 10 mg/kg IV over 2 hours every two weeks, and dexamethasone 40 mg PO q week. All pts received aspirin 325 mg PO daily. Prior to therapy pts underwent bone marrow biopsy and aspirate. MM and stromal cells were isolated for analysis of STAT 3 activation to assess the treatment’s effect on stromal/MM cell interactions. Clinical responses were assessed using IBMTR criteria. RESULTS: 17 pts have been enrolled, ages 53––89, with median number of previous regimens 3 (range 1–6). Two pts were taken off study during the first cycle, one due to GI perforation occurring d 6 of therapy, and one pt due to rapidly progressive disease during first week of therapy. Ten pts have completed ≥ 4 cycles and can be evaluated for response. Seven of 10 pts achieved a PR after a median of two cycles and have maintained that response. One pt progressed after completing one cycle, one pt progressed after 5 cycles, and one pt had stable disease after 6 cycles. Expected grade 3 toxicities included DVT in 2 patients (both of whom were on aspirin but received erythropoiesis stimulating agents) and 2 pts developed shortness of breath attributed to bevacizumab, with resolved after discontinuation of the drug; one patient developed atrial fibrillation which spontaneously converted. No patient developed hypertension or proteinuria. Most required a dose reduction of lenalidomide due to fatigue. Analysis of STAT3 DNA-binding in MM cells alone or in co-culture with MM-BMSCs revealed variable low levels of constitutive STAT3 activity and enhanced activity in co-culture. No additional effect of bevacizumab + revlimid on constitutive STAT3 activity was observed. CONCLUSIONS: the combination of lenalidomide, bevacizumab and low dose dexamethasone has activity in relapsed and refractory myeloma. The initial 70% response rate compares favorably with the 58% response rate reported by Stadtmauer et al (Blood 108:3552) in previously treated MM pts receiving lenalidomide and high dose dexamethasone. Toxicities of this regimen are predictable but manageable. The use of ESAs may contribute to the development of DVT and the protocol has been modified to preclude their use.

scholarly journals Pulsed high-dose dexamethasone treatment of polyneuropathy associated with monoclonal gammopathy

1997 ◽  
Vol 244 (7) ◽  
pp. 462-463 ◽  
Author(s):  
N. C. Notermans ◽  
H. M. Lokhorst ◽  
P. A. Van Doorn ◽  
L. H. Van den Berg ◽  
J. H. J. Wokke ◽  
...  
Keyword(s):  
Monoclonal Gammopathy ◽  
High Dose ◽  
Dexamethasone Treatment ◽  
High Dose Dexamethasone

Multiple myeloma and related conditions

2018 ◽  
Author(s):  
Graham Collins ◽  
Chris Bunch
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Cell Clone ◽  
Bone Marrow Failure ◽  
Organ Damage ◽  
End Organ Damage ◽  
Clonal Proliferation ◽  
Uncertain Significance

Multiple myeloma is a cancerous disorder of the bone marrow and arises from a clonal proliferation of plasma cells, resulting in end-organ damage (e.g. renal failure, hypercalcaemia, bone disease, and bone marrow failure). When a plasma cell clone is only detected in one site (either bony or soft tissue), it is termed a plasmacytoma. Monoclonal gammopathy of uncertain significance is also a clonal proliferation of plasma cells but, by definition, does not result in end-organ damage. This chapter addresses the diagnosis and management of multiple myeloma.

Autologous stem cell transplantation as a treatment modality for type 1 cryoglobulinemia in monoclonal gammopathy of renal significance.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19500-e19500
Author(s):  
Joshua Ryan Richter ◽  
Zhen Wang ◽  
David H. Vesole ◽  
Noa Biran ◽  
Michele Donato ◽  
...  
Keyword(s):  
Stem Cell ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
High Dose ◽  
Type I ◽  
Peripheral Blood Stem Cells ◽  
Post Transplant

e19500 Background: Type I cryoglobulinemia (CRYO) can be driven by disorders such as plasma cell dyscrasias. Monoclonal gammopathy of renal significance (MGRS) represents a group of kidney disorders characterized by the presence of a paraprotein; though not fitting the criteria for a hematologic malignancy. There exists no standard approach to manage these patients. Our patient is a 56-year-old man who was initially evaluated for edema. Workup revealed worsening renal function and proteinuria (Figure 1). Renal biopsy revealed abundant cryofibrinogen deposits and cryoglobulinemic glomerulonephritis with membranoproliferative pattern. Bloodwork showed type I (IgG Kappa) CRYO. Bone marrow evaluation revealed 7% clonal plasma cells. Further evaluation did not confirm a diagnosis of myeloma. Methods: Treatment was initiated with bortezomib, cyclophosphamide and dexamethasone. After 3 cycles of therapy the patient had normalization of his creatinine and marked improvement in edema. Peripheral blood stem cells were mobilized following the administration of high-dose cyclophosphamide (2gm/m2) plus filgrastim. He was subsequently conditioned for transplantation with high-dose melphalan (200mg/m2; HDM) followed by autologous stem cell rescue. He tolerated the procedure well without any unexpected toxicities; achieving prompt hematologic recovery Results: Evaluations post transplant revealed resolution of any circulating cryoglobulins and reduction in proteinuria. At 1 year post transplant, the patient has returned to his premorbid condition. Conclusions: Type 1 CRYO associated MGRS represents a complicated disorder for which there is no consensus treatment approach. As this process may be driven by clonal plasma cells, classical anti-myeloma therapy may provide a strategy for management. Given the typical low plasma cell burden in these patients, HDM has the potential to offer deep and durable remissions. Prospective studies are needed to validate this approach. [Table: see text]

scholarly journals Advances in MGUS diagnosis, risk stratification, and management: introducing myeloma-defining genomic events

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 662-672
Author(s):  
Ola Landgren
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
Low Risk ◽  
Intermediate Risk ◽  
Cell Percentage ◽  
Smoldering Myeloma ◽  
Monoclonal Proteins

Abstract In the 1960s, Dr Jan Waldenström argued that patients who had monoclonal proteins without any symptoms or evidence of end-organ damage represented a benign monoclonal gammopathy. In 1978, Dr Robert Kyle introduced the concept of “monoclonal gammopathy of undetermined significance” (MGUS) given that, at diagnosis, it was not possible with available methods (ie, serum protein electrophoresis to define the concentration of M-proteins and microscopy to determine the plasma cell percentage in bone marrow aspirates) to determine which patients would ultimately progress to multiple myeloma. The application of low-input whole-genome sequencing (WGS) technology has circumvented previous problems related to volume of clonal plasma cells and contamination by normal plasma cells and allowed for the interrogation of the WGS landscape of MGUS. As discussed in this chapter, the distribution of genetic events reveals striking differences and the existence of 2 biologically and clinically distinct entities of asymptomatic monoclonal gammopathies. Thus, we already have genomic tools to identify “myeloma-defining genomic events,” and consequently, it is reasonable to consider updating our preferred terminologies. When the clinical field is ready to move forward, we should be able to consolidate current terminologies—from current 7 clinical categories: low-risk MGUS, intermediate-risk MGUS, high-risk MGUS, low-risk smoldering myeloma, intermediate-risk smoldering myeloma, high-risk smoldering myeloma, and multiple myeloma—to future 3 genomic-based categories: monoclonal gammopathy, early detection of multiple myeloma (in which myeloma-defining genomic events already have been acquired), and multiple myeloma (patients who are already progressing and clinically defined cases). Ongoing investigations will continue to advance the field.

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