Mieloma de células plasmáticas secretor de IgD, un reto diagnóstico. Reporte de un caso

RESUMEN El mieloma de células plasmáticas secretor de IgD es una neoplasia de células plasmáticas poco frecuente y agresivo, generalmente afecta individuos más jóvenes que los demás mielomas. Es de difícil diagnóstico, ya que no se observa el pico de proteína monoclonal característico de los mielomas; no obstante, la inmunofijación, la cuantificación de IgD y el estudio de orina son pruebas de gran utilidad para su diagnóstico. Con respecto a las manifestaciones clínicas, es frecuente anemia, falla renal y múltiples lesiones óseas; además, la enfermedad tiene un curso agresivo, con poca respuesta a la quimioterapia convencional. A continuación, se describe un caso de una mujer de 57 años con antecedentes de dolor óseo y múltiples lesiones líticas óseas, quien fue diagnosticada con mieloma secretor de IgD a partir de la electroforesis de proteínas en suero, la inmunofijación en suero y orina, la cuantificación de IgD y el estudio medular. ABSTRACT Immunoglobulin D plasma cell myeloma is a rare and aggressive plasma cell disorder, which usually occurs in younger patients than other myelomas. Immunoglobulin D multiple myeloma is usually misdiagnosed because of the lack of a typical monoclonal protein spike; however, immunofixation electrophoresis, Immunoglobulin D serum levels and urine analysis are highly useful for diagnosis of the disease. Regarding clinical manifestations, patients commonly have anemia, renal failure, and multiple bone lesions. In addition, patients show an aggressive clinical course with poor response to conventional treatment and unfavorable prognosis. We report a 57 years-old female who presented with bone pain and multiple osteolytic bone lesions; according to serum protein electrophoresis, serum and urine immunofixation, IgD serum levels, and bone marrow biopsy, a final diagnosis of immunoglobulin D plasma cell myeloma was made. KEY WORDS Multiple myeloma, immunoglobulin D, renal insufficiency

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Paracoccidioidomycosis in children: clinical presentation, follow-up and outcome

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652004000300002 ◽

2004 ◽

Vol 46 (3) ◽

pp. 127-131 ◽

Cited By ~ 52

Author(s):

Ricardo Mendes Pereira ◽

Fábio Bucaretchi ◽

Eliana de Melo Barison ◽

Gabriel Hessel ◽

Antonia Teresinha Tresoldi

Keyword(s):

Treatment Effectiveness ◽

Clinical Manifestations ◽

Serum Levels ◽

Severe Malnutrition ◽

Bone Lesions ◽

First Line ◽

Lymph Node Enlargement ◽

Lytic Lesions ◽

Lymphoproliferative Syndrome

From February, 1981 to May, 2001, 63 children under 15 y old (ages 2 - 15 y, median = 8 y, mean ± 1 SD = 8 ± 3 y) presenting 70 episodes of Paracoccidioidomycosis were admitted. The main clinical manifestations and laboratory features observed upon admission were: lymph node enlargement (87.1%), fever (75.7%), weakness (48.6%), pallor (41.4%), hepatomegaly (40%), splenomegaly (35.7%), anemia (90%), hypergammaglobulinemia (88.5%), eosinophilia (75.5%) and hypoalbuminemia (72.5%). Moderate to severe malnutrition was detected in 35.7% of the episodes (Gomez's criterion). Radiographic and technetium studies showed bone lesions in 20 of the episodes, most of them being multiple lytic lesions, involving both long (70%) and plain bones (30%). First line treatment consisted of an association of sulfametoxazole-trimethoprin, which was used, exclusively, in 50 episodes. Follow-up of hemoglobin levels, number of eosinophils in the peripheral blood, albumin and gammaglobulin serum levels revealed significant sequential improvement one and six months after hospital admission, being quite useful to evaluate treatment effectiveness. Six patients died (9.3%) and four developed sequelae (6.3%) . In conclusion, the juvenile and disseminated forms can be observed in about 70% of the episodes of PCM occurring in children younger than 15 y old, most of them presenting with a febrile lymphoproliferative syndrome associated to anemia, eosinophilia and hypergammaglobulinemia.

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Clinical Significance of the Tumor Suppressor p53 Codon 72 Polymorphic Variants in Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.5102.5102 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5102-5102

Author(s):

Natalia C. Gonzalez-Paz ◽

Wee Joo Chng ◽

Shaji Kumar ◽

Tammy Price-Troska ◽

Scott Van Wier ◽

...

Keyword(s):

Multiple Myeloma ◽

Tumor Suppressor ◽

Plasma Cell ◽

Survival Data ◽

Clinical Manifestations ◽

Cellular Transformation ◽

Response To Treatment ◽

Codon 72 ◽

Number Of Patients ◽

Polymorphic Variants

Abstract Background: The p53 tumor suppressor gene has a common sequence polymorphism that results in either proline or arginine at amino-acid position 72. The Pro72 and Arg72 variants have been reported to differ in its functional activity. The Arg72 variant induces apoptosis more efficiently than Pro72 variant by its greater ability to localize to the mitochondria and increase the release of cytochrome c into the cytoplasm. In addition, recent studies have demonstrated that Arg72 variant was a better suppressor of cellular transformation, an activity believed to rely on the pro-apoptotic function of p53. Moreover, the Pro72 variant has been associated with a higher incidence of tumors. Aim: To evaluate the effect of the polymorphic variants of codon 72 and clinical outcome in patients with plasma cell malignancies. Patients and Methods: We analyzed 79 patients with plasma cell malignancies seen at Mayo Clinic between 2000 and 2003. Genomic DNA was extracted from CD138+ sorted plasma cell from bone marrow aspirates. PCR amplification of codon 72 and posterior sequencing was used for the analysis. Results: A total of 79 patients were analyzed. Thirty-four patients (34%) were heterozygous for p53, 57 (59%) homozygous for Arginine and 6 (6%) homozygous for Proline. The distribution among disorders was as follow, 52 patients had MM, 14 patients with SMM and 13 with MGUS. Among patient with MM 25% were Pro/Arg heterozygous, 71 % were Arg/Arg homozygous and 3.8% Pro/Pro homozygous. Survival data among MM patients and genotype were analyzed to Kaplan- Meier method. No significant differences were found among patients who carried homozygous (72R) or heterozygous genotype and overall survival. We exclude the analysis in MGUS and SMM for a low number of patients available. Conclusions: These findings indicate that codon 72 arginine p53 may not be associated with a prolonged survival in patients with Multiple Myeloma, but further study is needed to assess whether this polymorphism is associated with progression of MGUS to MM, age of onset, clinical manifestations, response to treatment etc.

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Serum Concentrations of DKK-1 Correlate with the Extent of Bone Disease in Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.3518.3518 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3518-3518

Author(s):

Martin Kaiser ◽

Maren Mieth ◽

Peter Liebisch ◽

Susanne Rötzer ◽

Christian Jakob ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Disease ◽

Serum Levels ◽

Conventional Radiography ◽

Bone Lesions ◽

X Rays ◽

Myeloma Bone Disease ◽

Lytic Lesions ◽

Significant Difference ◽

First Time

Abstract Objectives: Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells was reported to cause inhibition of osteoblast precursors. DKK-1 is an inhibitor of the Wnt/β-catenin signaling, which is a critical signaling pathway for the differentiation of mesenchymal stem cells into osteoblasts. So far there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions. Methods: DKK-1 serum levels were quantified in 184 previously untreated MM patients and 33 MGUS patients by ELISA, using a monoclonal anti-DKK-1 antibody. For the evaluation of bone disease, skeletal X-rays were performed. Results: Serum DKK-1 was elevated in MM as compared to MGUS (mean 11,963 pg/mL versus 1993 pg/mL, P < 0.05). Serum DKK-1 levels significantly correlated with myeloma stage according to Durie and Salmon (mean 2223 pg/mL versus 15,209 pg/mL in stage I and II/III, respectively; P = 0.005). Importantly, myeloma patients without lytic lesions in conventional radiography had significantly lower DKK-1 levels than patients with lytic bone disease (mean 3114 pg/mL versus 17,915 pg/mL; P = 0.003). Of interest, serum DKK-1 correlated with the number of bone lesions (0 vs. 1–3 vs. >3 lesions: mean 3114 pg/mL vs. 3559 pg/mL vs. 24,068 pg/mL; P = 0.002). Conclusion: This is the largest study of DKK-1 serum levels in multiple myeloma patients and data show for the first time a correlation between DKK-1 serum concentration and the amount of lytic bone disease, suggesting that DKK1 is an important factor for the extent of bone disease and supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

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IgM Multiple Myeloma: A Rare Subtype Highly Sensitive to Lenalidomide

Blood ◽

10.1182/blood.v112.11.5220.5220 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5220-5220

Author(s):

Alvaro Moreno-Aspitia ◽

Antony Charles ◽

Tejal Patel ◽

Celine Bueno ◽

Abba Zubair ◽

...

Keyword(s):

Multiple Myeloma ◽

Transient Response ◽

Low Dose ◽

Plasma Cells ◽

Poor Response ◽

Response To Therapy ◽

Bone Lesions ◽

Best Response ◽

M Spike

Abstract Background: IgM multiple myeloma (MM) are very rare plasmaproliferative disorders representing 0.5–1.2% of all cases of MM and < 0.2% of all IgM monoclonal gammopathies. Clinical criterion are not always helpful in differentiating IgM MM from Waldenstrom macroglobulinemia. However, the presence of lytic bone lesions, absence of lymphadenopathy and/or hepatosplenomegaly, presence of translocation of the immunoglobulin heavy chain locus at 14q32 [t(11;14), t(14;16), t(4;14)], and strong expression of CD138 by the plasma cells are useful in the diagnosis of IgM MM. It has been our experience and of others that these cases have an aggressive behavior at presentation, shorter survival than IgG and IgA MM and poor response to therapy for lymphoplasmacytoid lymphomas. We present here 2 cases of IgM MM with a dramatic response to Lenalidomide and low dose dexamethasone (Rev/Dex) Results: Baseline patient characteristics at time of diagnosis of IgM MM and therapy outcome are presented in the following 2 tables: Table 1. Case 1 2 Age and sex 72 (F) 73 (F) Serum M-spike (g/dL) 5.3 6.2 Urine M-spike (mg/dl/24 hrs) 72 412 Serum IgM (mg/dL) 8,590 11,000 BM plasma cells percentage 90 20 Plasma cell immunophenotyping CD138+++, partial CD20, CD56− CD138+++, partial CD20, CD56− Cytogenetics (Standard and/or FISH) Standard: normal FISH: not done on initial biopsy. On follow up there were insufficient number of plasma cells to perform test Standard: of 20 metaphases, 6 had a complex hypotetraploid karyotype with relative loss of 13q, 14, 15, 16, 20, and 22, and numerous unbalanced rearrangements. FISH: a plasma cell clone with monosomy 13 and IGH/c-MAF fusion, t(14;16). In addition, approximately 60% of plasma cells had a tetraploid clone with the same anomalies as well as relative loss of p53 Bone lesions Multiple non-traumatic spinal fractures and of stenum Several lytic lesions of long bones Renal insufficiency No No Anemia (Hbg g/dL) Yes (8.7) Yes (8.1) Hypercalcemia (Ca mg/dL) Yes (12.5) Yes (11.4) Beta 2 microglobulin (mg/dL) 5.79 8.51 Serum viscosity (cpoise) 5.9 4.8 Table 2. Best Response to therapy Case Therapy Best Response Comments 1 Rituxan, then Fludarabine based therapy Transient response Rapid progression after partial and transient response to each therapy 1 Lenalidomide + LD-Dex sCR after cycle #6. Currently on CR 18 months later IgM declined from 8,590 to 43 mg/dL after 4 cycles of Rev/Dex. 2 Lenalidomide + LD-Dex VGPR after cycle #2 IgM declined from 11,000 to 463 mg/dL after cycle 3. Complete disappearance of M-spike in serum; BM to be done after cycle #4 Conclusions: This is the first report that we are aware of a rapid and dramatic response to lenalidomide and low dose dexamethasone in these rare cases of IgM MM with poor response to NHL-type treatment. Lenalidomide-based therapy might abrogate poor prognosis cytogenetics in this unusual subtype of MM (case #2), however, follow up for this patient is still very short.

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Epidemiology and etiopathogenesis of multiple myeloma and monoclonal gammapathy of undetermined significance

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0012.7296 ◽

2018 ◽

Vol 72 ◽

pp. 953-965

Author(s):

Anna Suska ◽

Artur Jurczyszyn

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Genetic Predisposition ◽

Hematologic Malignancy ◽

Clinical Manifestations ◽

Bone Lesions ◽

First Degree Relatives ◽

Monoclonal Gammapathy ◽

Increased Risk ◽

Undetermined Significance

Multiple myeloma (MM) accounts for about 13% of haematological malignancies. Etiopathogenesis is still not fully understood. Confirmed risk factors include the following: age, male sex, black race and MM among first-degree relatives. MM may be preceded by monoclonal gammapathy of undetermined significance (MGUS). The risk of progression is about 1% per year. Genetic changes, proinflammatory and proangiogenic cytokines and some infections may play a role in this risk. With regard to lifestyle risk factors, only obesity and overweight were associated with increased MM incidence and elevated risk for transformation of MGUS to MM. Regarding occupational exposure, there is an increased risk of MM among farmers, firefighters and hairdressers. As far as autoimmune diseases are concerned, only ankylosing spondylitis and pernicious anemia are associated with significantly increased MM risk. Increased risk of MM was also reported in relatives of MM patients, especially in first-degree relatives and in African-American families. The risk of MGUS is elevated in both first-degree relatives of MM and MGUS patients. Data from genetic analysis indicated translocations involving immunoglobulin heavy chain (IGH) loci, hyperphosphorylation of several proteins which are the targets for paraproteins produced by malignant plasma cells and single nucleotide polymorphisms (susceptibility loci) as the potential genetic predisposition to multiple myeloma. The mechanism of heterogeneity of clinical manifestations of MM is not known. Anemia is less frequent in patients whose relatives were diagnosed with hematologic malignancy compared to those with a negative family history. In patients from a younger age group, osteolytic bone lesions were more common than in older patients. In conclusion, environmental exposures modify the genetic predisposition to MM and MGUS.

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Plasma Cell Dyscrasias in HIV, Epidemiology, Presentation and Treatment Characteristics and Its Strong Association with Hepatitis C- Report Form a Large HIV Cohort

Blood ◽

10.1182/blood-2018-99-119222 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5607-5607

Author(s):

Nishi Shah ◽

Sakshi Jasra ◽

Ana Acuna-Villaorduna ◽

Urvi A Shah ◽

Gurbakhash Kaur ◽

...

Keyword(s):

Multiple Myeloma ◽

Retrospective Study ◽

Plasma Cell ◽

Heavy Chain ◽

Autologous Transplantation ◽

Bone Lesions ◽

Cell Transplant ◽

Hiv Diagnosis ◽

Plasma Cell Dyscrasias ◽

Successful Outcomes

Abstract Introduction: As people with HIV live longer, the epidemiology of plasma cell disorders (PCD) including MGUS, smoldering myeloma and Multiple myeloma (MM) becomes relevant and remains unknown. Moreover, patients with HIV have a higher incidence of monoclonal proteins which may not be related to an underlying lymphoproliferative disorder[1, 2] . There are mostly anecdotal reports and very few studies in HIV myeloma[3]. A retrospective study of 10 patients with HIV+ve symptomatic MM reported possible therapeutic benefit of ART and reported better overall survival of HIV+ve MM on ART as compared to HIV -ve MM. There is a paucity of data in PCD in this population whose incidence can be expected to increase globally. We conducted a single-institution retrospective study to look at the incidence of PCD. Methodology:We reviewed an electronic database of patients with HIV related PCD treated at Montefiore Medical Center between 2001 and 2018. All patients with a new diagnosis of PCD between January 1 2001 to July 15 2018 were identified. Data on patient demographics, HIV status, clinical outcomes (including mortality) and therapy was collected. Results: Between 2001 and 2018, 14438 patients were identified with HIV and 1986 patients had a monoclonal band in SPEP (13.8%). Based on our previous study, patients who had a definitive monoclonal band or suspected MM underwent a BM biopsy. 34 patients were diagnosed with PCD --MGUS 16 (47.05%), Smoldering MM 1 (2.94%), MM 16 (47.05%) and Primary plasma cell leukemia (PCL) 1 (2.94%). The majority of the patients were AA consistent with demographics of the Bronx. Interestingly HCV co-infection was identified in 50% (n=17) of patients and HBV co-infection was present in 15% (n=5) patients. The median CD4 count was 381 (12-1080), median viral load 237 (0-501534) and 53% patients were on ART at the time of diagnosis. The median time from HIV diagnosis was 13.9 (-2.8 to 29) years. In patients with MGUS the predominant heavy chain involvement was IgG, the median protein on SPEP was 1.1 g (0.7-1.9 g) and percentage of BM involvement was 5% (2-10%). In patients with MM IgG was the predominant heavy chain involved. On presentation, ISS Stage was Stage I in 2 patients (15.4%), 4 (30.7%) had at least Stage 2, 7 patients (53.9%) had stage 3. On presentation, 10 (58.8%) patients presented with anemia, 10 (58.8%) presented with renal impairment (Cr>=1.3), 16 (94.1%) presented with bone lesions, 6 (37.5%) presented with hypercalcemia. 5 patients (34.6%) had extramedullary presentation including 1 patient (2.9%) with PCL, 2 (5.8%) with anaplastic plasmacytoma. All patients were treated with an imid or bortezomib based regimen and there were no unusual side effects in these patients. 5 patients (29.4%) underwent autologous stem cell transplant with successful outcomes. Discussion: The prevalence of a positive SPEP is 13.8% in patients with HIV and the prevalence of plasma cell dyscrasias (PCD) in our population is 0.02%. A previous study from this cohort[2] showed that approximately 6.4% of patients with a positive SPEP developed hematological malignancy and all patients with a faint monoclonal band had lymphoma (70.5%) and those with a definite monoclonal band had myeloma (29.5%). Even though prevalence is less than the general population rate of 3%, as patients with HIV live longer this number may increase. In our study there was a high rate of co-infection with HCV in patients who had a PCD and this needs further investigation to determine causality. PCD developed at a median of 13.9 years after HIV diagnosis. The ISS staging distribution in patients presenting with myeloma is consistent with non HIV myeloma. People with HIV tolerate standard imid or proteasome inhibitor based triple drug therapy and have successful outcomes with autologous transplantation. This is the largest cohort and report describing PCD in HIV population. References:Jou, E., et al., Viral co-infections and paraproteins in HIV: effect on development of hematological malignancies. Ann Hematol, 2016. 95(4): p. 575-80.Jou, E., et al., Retrospective study of the prevalence and progression of monoclonal gammopathy in HIV positive versus HIV negative patients. Hematol Oncol, 2017. 35(1): p. 64-68.Li, G., et al., A retrospective analysis of ten symptomatic multiple myeloma patients with HIV infection: A potential therapeutic effect of HAART in multiple myeloma. Leukemia Research, 2014. 38(9): p. 1079-1084. Disclosures Janakiram: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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Clinical implication of PET/CT and skeletal bone survey in evaluation of multiple myeloma and related monoclonal disorders.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18574 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18574-e18574

Author(s):

Muhammad Jawad Popalzai ◽

Homam Alkaied ◽

Maryah Mansoor ◽

Arnold Brenner ◽

Qun Dai

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Skeletal Survey ◽

Whole Body ◽

Bone Lesions ◽

Positive Finding ◽

Pet Ct ◽

Plasma Cell Disorders ◽

Smoldering Myeloma

e18574 Background: Whole body skeletal x-ray is considered a gold standard for detecting bone lesions in patients with plasma cell disorders. PET/CT has been increasingly used but its role is yet to be defined. We conducted this study to compare the role of these two imaging modalities in evaluation of plasma cell disorders. Methods: This is single institution, retrospective study to evaluate the role of skeletal survey and PET/CT in patients with multiple myeloma, smoldering myeloma and MGUS. Patients’ records, imaging reports and subsequent management plan were reviewed and compared. Results: A total of 16 patients were reviewed. Among them, 11 patients had multiple myeloma, 2 had smoldering myeloma, and 3 had MGUS. 7/11 patients with multiple myeloma had concordant findings on skeletal survey and PET. 3 of these patients had negative skeletal surveys but had positive finding on PET/CT. PET/CT also identified plasmacytomas in 2 patients. In 2 patients with smoldering myeloma, both skeletal survey and PET/CT were negative. 2/3 patients with MGUS had lytic lesions on skeletal surveys which were not revealed by subsequent PET/CT’s. Both patients were observed without treatment and at 2 years follow up did not show disease progression. Conclusions: Our retrospective analysis showed that skeletal survey is still important for base-line evaluation of bone lesions in multiple myeloma and related monoclonal disorders. PET/CT is more sensitive for detection of bone lesions and can also detect extraosseous lesions such as plasmacytomas. Using tumor metabolic activity, PET/CT may improve diagnostic accuracy and is complementary to conventional skeletal survey. [Table: see text]

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Influence of Renal Failure on the Osteoprotegerin Level in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.4999.4999 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4999-4999

Author(s):

Stefcho Goranov ◽

Veselina Goranova-Marinova ◽

Emil Kumchev ◽

Pavel Pavlov ◽

Todorka Tzvetkova

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Clinical Stage ◽

Correlation Coefficients ◽

Serum Levels ◽

Function Parameter ◽

Renal Diseases ◽

Bone Lesions ◽

Low Grade ◽

Phase Dynamics

Abstract The aim of the study is to analyse the osteoprotegerin (OPG) level in patients with multiple myeloma (MM), primary renal diseases with renal failure (PRD with RF) and healthy controls and to assess the influence of RF on the correlations of OPG with basic parameters for MM. Serum levels of OPG (ELISA kits, Biomedica, Vienna) were studied in 66 newly diagnosed patients with MM, 51 with PRD and RF and 32 controls. In MM patients OPG is presented also as OPG/creatinin ratio and is studied acc to the clinical stage (Durie and Salmon), bone marrow infiltration, grade of myeloma bone disease (MBD) using the Merlini scale, b2-microglobulin and LDH. Statistics were done by SPSS v 11.0 (variative, alternative, correlative, non-parametric analyses, Mann-Whitney test, one-way ANOVA; at p<0,05). OPG levels in MM patients do not differ from PRD with RF group but are significantly higher compared with the controls (tabl.1). OPG/creatinin eliminates the difference between the MM patients and controls: 0,043±0,003 vs 0,037 ± 0,001, p>0,05. In patients with PRD OPG is significantly higher in II gr. RF (p<0,02) while in MM patients its level does not depend on the grade of RF. In I clinical stage OPG is significantly higher than in III stage (6,34 ± 0,724 vs 4,245 ±0,407 pmol/l, p<0,03). MM patients with RF have significantly higher OPG than these without RF. The proportion of MM patients with RF and elevated OPG >6,0pmol/l is about 2,5 times higher (68,7%) than the proportion of patients with low OPG<3,44pmol/l (25,0%), p<0,05. MM patients with minimal and no bone lesions+RF have significantly higher OPG than these with severe MBD + RF (9,97 ± 2,42 vs 4,92 ± 0,62 pmol/l, p<0,05). The correlations of OPG are stronger for OPG/creatinin and are most expressed in the MM group without RF. RF “masques” the clinical correlations of OPG (tabl.2). OPG levels in MM show phase dynamics: initial elevation in early clinical stages and low grade bone lesions (successful counteraction to intensive bone resorbtion) followed by decrease in the advanced stages and severe MBD. These data we explain with the combined but opposite effects of RF (elevates OPG providing skeletal resistance in uremia) and the specific, not-possible-to overcome action of myeloma tumor burden (directly degrades OPG and inhibits osteoblast function). OPG levels in patients with MM, PRD and controls Groups N OPG pmol/l mean±SEM P *vs controls Controls 32 3,77 ± 0,33 0,01 MM 66 5,36± 0,45 MM without RF 39 4,51 ± 0,30 0,001 MM with RF 27 6,60 ± 1,00 MM with I gr RF (cr 166–353 mol/l) μ 18 6,73 ± 1,37 NS MM with II gr RF (cr 353– 707 mol/l) μ 9 6,20 ± 1,32 PRD with RF 51 5,74± 0,36 0,001* PRD with I gr RF 23 4,50± 0,32 0.02 PRD with II gr RF 28 6,75± 0,51 Correlation coefficients of OPG in MM and eliminating the influence of renal function Parameter OPG pmol/l OPG/creatinin OPG pmol/l (without RF) p r p r p r Clinical stage <0,05 −0,275 <0,001 −0,616 <0,001 − 0,669 MBD <0,05 −0,323 <0,001 −0,521 <0,001 − 0,556 m. infiltration N.S. <0,001 −0,530 <0,001 − 0,562 ß2-microglobulin <0,05 +0,375 N.S N.S LDH N.S N.S <0,05 −0,338

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IgM Multiple Myeloma: Disease Definition, Prognosis, and Differentiation From Waldenstrom's Macroglobulinemia.

Blood ◽

10.1182/blood.v114.22.1828.1828 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1828-1828 ◽

Cited By ~ 2

Author(s):

Steven Schuster ◽

Angela Dispenzieri ◽

S. Vincent Rajkumar ◽

Alvaro Moreno Aspitia ◽

Robert Kyle ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Monoclonal Gammopathy ◽

Median Overall Survival ◽

Bone Lesions ◽

Lytic Lesions ◽

Lytic Bone Lesions ◽

Plasma Cell Disorder ◽

Definition Of ◽

Cell Disorder

Abstract Abstract 1828 Poster Board I-854 Background IgM Multiple Myeloma (MM) and Waldenstrom's Macroglobulinemia (WM) are two hematologic diagnoses with the common variable of an IgM monoclonal gammopathy. Distinguishing these two diagnoses is critical as the approach to therapy is different. A study by Avet-Loiseau et al demonstrated the presence of t(11;14) translocations in 7 of 8 patients with IgM MM that was absent in all of a series of 17 cases of WM (Semin Oncol 2003 30:2;153). However, 6 of the 8 IgM MM cases lacked classic lytic lesions. Method A priori, based on the literature and the natural history of MM, we defined IgM MM as a symptomatic clonal plasma cell proliferative disorder characterized by a serum IgM monoclonal protein (regardless of size) plus presence of t(11;14) on fluorescent in situ hybridization (FISH) and/or lytic bone lesions felt to be related to the underlying plasma cell disorder. The cases for the study were screened by a computerized database search for ‘IgM’ and ‘Myeloma’ of all patients seen at Mayo Clinic in the last 30 years at all three sites (Rochester, Arizona and Florida). Patients identified on the computerized screen were then audited by chart review to identify the study cohort. Results 38 cases were identified on initial screen of the computerized database as potential patients with IgM MM. Of these, a total of 22 cases met our specific definition of IgM myeloma (t(11;14 and/or lytic lesions). Of the remaining 16 cases, 8 were IgM MGUS, 5 were WM based on clinical presentation (hyperviscosity, lymphadenopathy and organomegaly) and biopsy findings of lymphoplasmacytic lymphoma, 1 was excluded due to lack of information, and the remaining 2 patients were indeed considered to have clinical IgM MM. Interestingly, these two patients did not have either the t(11;14) or lytic lesions, but rather had immunophenotypic features suggestive of MM and not WM (CD138+, CD20-). Table 1 summarizes the clinical characteristics of the 22 patients who met our criteria for IgM MM. All 22 patients had lytic bone lesions. Of the 17 evaluated with FISH, 6 (35%) demonstrated the t(11;14) abnormality. Median overall survival by Kaplan-Meier analysis was 37 months represented in Figure 1. Conclusion IgM MM is a discrete clinical entity that can and should be distinguished from WM. Our definition of IgM MM is designed to be specific and requires the presence of a symptomatic IgM secreting plasma cell proliferative disorder plus presence of t(11;14) and/or lytic bone lesions felt related to the underlying plasma cell disorder. In this, the largest series of patients with IgM MM, the t(11;14) abnormality is very specific for IgM MM, but may not be sensitive, being present in approximately 1/3 of patients. The median overall survival is similar to non-IgM myeloma patients treated during this period, and much shorter than what would be expected for WM. The minority of symptomatic patients with IgM monoclonal gammopathy who do not meet this criteria, but have immunophenotypic features more suggestive of MM rather than WM need further study. Disclosures No relevant conflicts of interest to declare.

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Secretome Analyses of Primary Bone Marrow Fibroblasts Isolated From MGUS and Multiple Myeloma Show a Stepwise Occurrence of Alterations.

Blood ◽

10.1182/blood.v114.22.1801.1801 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1801-1801

Author(s):

Johannes Drach ◽

Astrid Slany ◽

Thomas Mohr ◽

Johannes Griss ◽

Christoph C Zielinski ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Growth Factor ◽

Plasma Cell ◽

Conflicts Of Interest ◽

Cell Clone ◽

Serum Levels ◽

Plasma Cell Dyscrasia ◽

Healthy Donors ◽

Bone Marrow Fibroblasts

Abstract Abstract 1801 Poster Board I-827 The microenvironment of tumor cells in the bone marrow was demonstrated to contribute to tumor promotion and survival. The role of bone marrow fibroblasts (BMFs) in supporting the malignant plasma cell clone in multiple myeloma (MM) has been established, but it remains unclear to which extent the BM microenvironment in general and BMFs in particular are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. Therefore we performed proteomics studies on the secretome of BMFs isolated from healthy donors, patients suffering from MGUS and patients suffering from MM. Compared to normal background, BMFs derived from MGUS secreted elevated levels of proteins indicating mitogenic activity and moderate inflammation. These proteins included periostin, IL-6, CXCL5 and CSF-1. Insulin-like growth factor II, which is normally not expressed by normal BMFs, was secreted by BMF cells derived from MGUS as well as from MM. In addition to those and other proteins, BMF cells derived from MM were found to specifically secrete stem cell growth factor, MMP-28 and stanniocalcin-1. These data indicate a step-wise alteration of BMF secretion activity related to the stage of the underlying plasma cell dyscrasia. Therefore BMF might support the progression from MGUS to MM. In order to correlate the secretion performance of BMF with blood serum levels of candidate marker proteins, Luminex assays are employed. Based upon these results, it is our aim to identify serum biomarkers which allow to assess the functional state of BMF and thus the risk for the progression of MGUS to MM. Disclosures No relevant conflicts of interest to declare.

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