Clinical Manifestation Of Multiple Myeloma Research Articles

Epidemiological data, etiology, pathogenesis, risk factors, clinical manifestations, modern methods of diagnosis and treatment, prediction of the course of multiple myeloma (literature review)

Background. Multiple myeloma (MM) is a neoplastic disease with a multistage course characterized by uncontrolled, multifocal proliferation of monoclonal plasma cells in the bone marrow, which produce monoclonal immunoglobulin or only its fragments, which lead to destruction of bone tissue and organ damage. Quite high rates of both morbidity and mortality from MM require more careful attention and deeper scientific research of this problem. Objective of the article is to investigate the epidemiology, etiology, pathogenesis, risk factors, clinical manifestations, modern methods of diagnosis and treatment, and also prediction of the course of MM. Methods. The following research methods were used: search, extraction and processing of information; assessment of the quality of sources; systematic literature review; content analysis. Research materials are thematic publications of ukrainian and foreign scientists. Results. MM accounts for ~1% of all malignant neoplasms and ~14% of hematological neoplasms worldwide. Etiological factors of MM: genetic predisposition, bacterial or viral infections, ionizing radiation, carcinogenic toxins. The clinical syndrome of MM is characterized by hypergammaglobulinemia, hypercalcemia, susceptibility to infections, and pathological fractures. Diagnosis of MM includes: general analysis of peripheral blood; diagnosis of serum and urine proteins; aspiration biopsy and trepanobiopsy of bone marrow; cytogenetic and molecular diagnostics; other laboratory diagnostics; radiography, CT, MRT and PET-CT. The main methods of treatment of MM: radiation therapy, chemotherapy, combined CT with the inclusion of new drugs, HDCT + autologous THSC. Prediction of the course of MM depends on the R-ISS stage, LDH level and high-risk cytogenetics. Conclusion. During the last years of modern oncohematology, we observe scientific achievements in the diagnosis and treatment of MM. A thorough study of the epidemiology, etiology and pathogenesis, risk factors and clinical manifestations of MM contribute to effective diagnosis and selection of the optimal treatment strategy and tactics, as well as determining the prognosis of the course of MM.

A Stepwise Screening Protocol for Multiple Myeloma

Monoclonal gammopathies and multiple myeloma should be screened in the primary care setting. The screening strategy consisted of an initial interview supported with the analysis of basic laboratory test results and the increasing laboratory workload in the following steps was developed based on characteristics of patients with multiple myeloma. The developed 3-step screening protocol includes evaluation of myeloma-related bone disease, two renal function markers, and three hematologic markers. In the second step, the erythrocyte sedimentation rate (ESR) and the level of C-reactive protein (CRP) were cross-tabulated to identify persons qualifying for confirmation of the presence of monoclonal component. Patients with diagnosed monoclonal gammopathy should be referred to a specialized center to confirm the diagnosis. The screening protocol testing identified 900 patients with increased ESR and normal level of CRP and 94 of them (10.4%) had positive immunofixation. The proposed screening strategy resulted in an efficient diagnosis of monoclonal gammopathy. The stepwise approach rationalized the diagnostic workload and cost of screening. The protocol would support primary care physicians, standardizing the knowledge about the clinical manifestation of multiple myeloma and the method of evaluation of symptoms and diagnostic test results.

Advances in the pathogenesis of multiple myeloma bone disease.

Multiple myeloma (MM) is a clonal proliferative malignant tumor of plasma cells in bone marrow. With the aging of population in China, the incidence of MM is on the rise. Multiple myeloma bone disease (MBD) is one of the common clinical manifestations of MM, and 80%-90% of MM patients are accompanied by osteolytic lesions at the time of their first visit to the clinic. MBD not only increases the disability rate of patients, but also severely reduces the physical function of patients due to skeletal lesions and bone-related events. Currently available drugs for treating of MBD are ineffective and associated with side effects. Therefore, it is important to find new therapeutic approaches for the treatment of MBD. It is generally believed that the increased osteoclast activity and suppressed osteoblast function are the main pathologic mechanisms for MBD. However, more and more studies have suggested that soluble molecules in the bone marrow microenvironment, including cytokines, extracellular bodies, and metabolites, play an important role in the development of MBD. Therefore, exploring the occurrence and potential molecular mechanisms for MBD from multiple perspectives, and identifying the predictive biomarkers and potential therapeutic targets are of significance for the clinical treatment of MBD.

Advances in Biomarkers for Multiple Myeloma

Multiple myeloma (MM) is the second most common malignancy in hematology. MM is characterized by the malignant proliferation of plasma cells in the bone marrow, accompanied by the secretion of monoclonal immunoglobulin, mainly occurring in the elderly. The clinical manifestations of MM include renal dysfunction, bone destruction, infection, anemia, hemorrhage, hypercalcemia, and hyperviscosity syndrome. The recent discovery of biomarkers related to the diagnosis or prognosis of MM provides an important basis for the diagnosis and treatment of MM. This paper reviews the research progress of biomarkers expressed in tissues and peripheral blood at home and abroad.

The role of monoclonal antibodies in treatment of refractory multiple myeloma

Multiple myeloma (MM) is a B-cell malignant tumor; its morphological substrate – plasma cells – produces monoclonal immunoglobulin. Primarily, MM is diagnosed in elderly people and is characterized by a variety of clinical manifestations caused by plasma cells infiltration and organ damage. Despite successes in MM therapy, in the majority of cases recurrences of MM or refractory process are observed. In this case, the choice of antitumor drug is usually made depending on its tolerability, toxicity, and availability. Selection of correct treatment can be complicated by such frequent clinical manifestations of MM as osteolytic vertebral lesions leading to development of pathologic compression fractures which in some cases cause spinal cord compression and full immobility in the patients with MM.A clinical case of a 62-year-old female patient with refractory MM is presented. Pathologic compression fractures of the Th12 and L2 vertebral bodies with massive extraosseous component at the Th12 vertebra level posed a threat of spinal cord compression. At the 1st stage, percutaneous vertebroplasty was performed, then antitumor therapy with daratumumab without increased intercycle intervals which significantly increased patient’s quality of life.

Digital Necrosis as Initial Manifestation of Multiple Myeloma: An Unusual Case Report

Clinical manifestations of multiple myeloma are variable. The authors report a 68-year-old female who presented to the hospital with bilateral digital necrosis and dry gangrenous toes in both left and right feet. She was diagnosed with IgA-λ multiple myeloma associated with Type I cryoglobulinaemia. Emergency management consisted in hyperhydration (plasmapheresis was not available) and thromboprophylaxis. Necrotic digits were amputated. Chemotherapy (bortezomib, lenalidomide, and dexamethasone) was started with good initial evolution. This uncommon presentation can easily be missed, and clinicians should be aware of a possible underlying malignancy.

Renal failure in patients with hematological malignancies (literature review)

Dysfunction of the natural detoxification organs remains a significant problem in patients with hematological malignancies. The reasons for the development of renal failure are associated with the individual characteristics of the malignant process, the patient’s comorbid background, the toxic effects of anticancer treatment and its complications. The efficacy of many anticancer drugs correlates with their dose, an increase in which is associated with increased toxic effects on healthy organs, including the kidneys. The main reasons for the renal failure development in hematological cancer patients and syndromes that prevent adequate antitumor therapy are considered. Diagnostic algorithm optimization and supportive intensive care of acute renal failure is the key to the successful application of highly effective modern protocols of drug anticancer treatment.A special group is represented by patients suffering from monoclonal gammopathies with acute renal injury and hyperproduction of immunoglobulins free light chains. Renal failure can be the onset and dominant clinical manifestation of multiple myeloma in 18–56 % of cases, of which 10 % require programmed hemodialysis. Antitumor therapy in presence of renal failure is limited, and in some cases impossible, while the renal function recovery is associated with an increase in survival.Organ damage in oncohematological patients can be a manifestation of paraneoplastic syndromes. Tumor lysis syndrome is an urgent problem of oncohematological practice associated with the development of acute renal injury and high mortality.The development of organ failure in oncohematological patients causes significant difficulties in antitumor therapy; a combination of organ dysfunction and the resulting change in anticancer therapy regimens worsen the prognosis. Modern methods of organ failure prevention and treatment can successfully solve complex clinical problems.

Association between Kidney Function, Proteinuria and the Risk of Multiple Myeloma: A Population-Based Retrospective Cohort Study in South Korea.

PurposeWhile renal impairment is one of the first clinical manifestations of multiple myeloma (MM), declined renal function may conversely be a risk factor for cancers including MM. In this study, we investigated the relationship between chronic kidney disease and MM at a population level.Materials and MethodsA total of 9,809,376 adults who participated in a nationwide health screening program and had no MM, cancer or end-stage renal disease at baseline were investigated for incidence of MM. The impact of estimated glomerular filtration rate (eGFR) and random urine dipstick proteinuria, and interactive associations of the two factors on the MM incidence were evaluated.ResultsThe general incidence of MM was 4.8 per 100,000 person-years (mean follow-up of 8.3 years). Participants with eGFR < 60 mL/min/1.73 m2 (5.8% of participants) had higher MM incidence than those with eGFR ≥ 60 mL/min/1.73 m2 (adjusted hazard ratio, 1.29; 95% confidence interval, 1.17 to 1.43). When eGFR was graded into five levels, there was a significant inverse dose-response relationship between eGFR level and MM incidence at the lower eGFR levels (reference: eGFR 60–89 mL/min/1.73 m2). A dose-response relationship was also found with degree of dipstick proteinuria and incidence of MM.ConclusionAdults with decreased renal function indicated either by decreased eGFR or presence of proteinuria are at a higher risk of developing MM compared to those without, and there is a dose-response relationship between the severity of renal impairment and MM incidence.

A case report of scrotal mass the first clinical manifestation of multiple myeloma

A case report of scrotal mass the first clinical manifestation of multiple myeloma

Intractable hypercalcemia in a patient with multiple myeloma: An infectious etiology

Hypercalcemia is a common laboratory finding in patients with malignancy, as well as with granulomatous disease. We report the case of a 75-year-old man with multiple myeloma (MM) who presented with generalized weakness, fever, and intractable hypercalcemia. The hypercalcemia proved difficult to treat despite well-controlled MM, as well as adequate use of bisphosphonates and calcitonin. Biopsy of sub-centimeter mesenteric adenopathy was significant for Histoplasma capsulatum and negative for malignancy, suggesting disseminated gastrointestinal histoplasmosis as the sole etiology for uncontrolled hypercalcemia. He was successfully treated with voriconazole. Disseminated histoplasmosis can be fatal if left untreated and warrants vigilance of non-malignant etiologies of hypercalcemia. While hypercalcemia is a common clinical manifestation of MM, our patient is an exemplar of maintaining a broader differential diagnosis in immunocompromised hosts.

Role of Pregabalin in Treatment of Polyneuropathy in Multiple Myeloma Patients: A Retrospective Study.

Polyneuropathy (PN) is a frequent and significant clinical manifestation of multiple myeloma that may be observed at onset of disease or induced during treatment as a therapy-related complication. Polyneuropathy may be a relevant issue in myeloma patients owing to its significant impact on the quality of life, considering that it may lead to dose reduction or treatment discontinuation. The present retrospective study intended to evaluate efficacy of pregabalin (PGB) in treatment of PN in multiple myeloma patients. Medical charts of 108 consecutive PN myeloma patients were reviewed. Data regarding the tumor history and therapy as well as the clinical and neurophysiological examinations 6 months before and after initiation of PGB therapy were collected. Thirty-eight medical charts had all the requested information. All patients (n = 38) underwent bortezomib-based treatment; 19 were previously treated and 19 were treatment naive. At first neurologic visit, all patients had PN symptoms (grade 2 of National Cancer Institute-Common Toxicity Criteria) without relevant pain. Neurophysiological evaluation showed a significant decrease in sensory nerve action potential amplitude (P = 0.006), conduction velocity (P = 0.006), and distal latency (P = 0.03) of sensory nerves between the first and the last neurological examination, in all patient population. Similar results were observed in treatment-naive patients, when the study cohort was stratified according to previous treatment. On the contrary, no significant differences were found between the first and the last neurophysiological follow-up evaluation in previously treated patients. Six months after PGB treatment, all patients reported disappearance of neurological symptoms (grade 0 National Cancer Institute-Common Toxicity Criteria). In this retrospective study, improvement in neurological symptoms during PGB therapy was observed in the total population, despite the presence of a distal, sensory axonal neuropathy, as evidenced by neurophysiological examination.

Epigenetics of Multiple Myeloma Bone Disease

Multiple myeloma bone disease (MMDB) is a devastating clinical manifestation of multiple myeloma associated with excessive bone osteolysis, which results from enhanced osteoclastogenesis and suppression of bone marrow stromal cell (BMSC) differentiation into osteoblasts. Impaired osteogenesis and functional alterations of myeloma-exposed BMSCs (MM-BMSCs) during the course of disease evolution significantly contribute to myeloma growth, metastasis, and chemoresistance. This review highlights new studies demonstrating that epigenetic modalities including chromatin-mediated gene silencing and non-coding RNA contribute to pathogenesis of MM-BMSCs. Inhibitors targeting histone-modifying enzymes EZH2, JMJD3, HDACs, and BET proteins have been successfully used to revert osteogenic suppression of MM-BMSCs. Aberrant expression of non-coding RNA cause functional changes associated with senescence, osteogenic suppression, and tumor-promoting phenotype of MM-BMSCs. Epigenetic events guiding transformations of the surrounding BMSC compartments are ultimately linked to disease onset and progression and open new therapeutic opportunity to target dissemination of MM tumors and reliably repair bone lesions.

Corrected calcium versus ionized calcium measurements for identifying hypercalcemia in patients with multiple myeloma

BackgroundDysregulated bone turnover is an important clinical manifestation of multiple myeloma (MM), and 30% of patients present with hypercalcemia. Serum calcium levels are routinely monitored using total calcium measurements corrected for albumin. However, myeloma-related paraproteins may bind calcium, confounding these measurements. Patients and methodsWe retrospectively analyzed correlation between corrected calcium and ionized calcium in a sample of patients with MM and a control sample of patients with breast or non-small cell lung cancers (n = 200). Multiple linear regression was used to identify variables affecting corrected calcium measurements. ResultsCorrelation between corrected calcium and ionized calcium was stronger in the control group compared to the MM group (Spearman correlation coefficient 0.85 versus 0.76, respectively). Sensitivity of corrected calcium in identifying hypercalcemia defined by elevated ionized calcium was 36% in patients with MM and 76% in the control group. Multiple linear regression did not reveal variables significantly influencing corrected calcium in the MM group, although serum paraprotein trended toward significance (p = 0.09). ConclusionIonized calcium may be better than corrected calcium for detecting hypercalcemia in patients with MM. Additional analyses are needed to better quantify the clinical impact of paraprotein calcium-binding.

Epidemiology and etiopathogenesis of multiple myeloma and monoclonal gammapathy of 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.

Prognostic value of 1q21 amplification in multiple myeloma

To determine the prevalence of amp1q21 and its relationship to the clinical manifestations of multiple myeloma (MM). In December 2009 to March 2016, a total 134 patients aged 30 to 81 years (median 57 years) underwent a pretreatment FISH-study of bone marrow (BM) with centromeric and locus-specific DNA probes to identify amp1q21, t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), trisomies of chromosomes 5, 9, 15, del13q14, del17p13/TP53, and t(8q24)/cMYC. Induction therapy with bortezomib-containing cycles was performed. Autologous stem cell transplantation was carried out in 48 patients. The median follow-up of patients was 19.3 months (3.2-77.4 months). Disease progression was diagnosed in 69 (51.5%) patients; 12 patients also underwent FISH study during disease progression. At the onset of MM, amp1q21 was detected in 53 (39.6%) patients. The overall 5-year survival rate in patients with amp1q21 was almost 2 times lower than that in those without amp1q21 (43.5 and 79.4%, respectively; p=0.07). The overall 5-year survival rate in patients with one extra copy of 1q21 (only 3 copies) was 67.3%, that in those with 2 or more extra copies of 1q21 (only 4-7 copies) was 20.9% (p=0.0016). Nine (75%) of the 12 patients examined during disease progression were found to have amp1q21: 2 cases were detected in the period of progression to have amp1q21 in its absence at disease onset; 7 cases had amp1q21 both at MM onset and progression; however, the number of copies of 1q21 was unchanged. Аmp1q21 is one of the most common chromosomal abnormalities in patients with new-onset MM and may appear in the course of disease progression. The presence of аmp1q21 is an important prognostic factor and must have to be included in the diagnostic study both at disease onset and progression.

Impact of CRAB Symptoms in Survival of Patients with Symptomatic Myeloma in Novel Agent Era.

The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents. In the current study, patients with hypercalcemia and bone disease showed a significantly worse prognosis, whereas anemia and renal failure showed no difference in survival. Novel agents used for treatment of patients with renal failure suggested a favorable outcome compared with conventional therapy. Bone disease was the most common factor and may have the strongest prognostic value in symptomatic myeloma patients using novel agents.

Prospective Investigation of Genetic Alterations in Osteolytic Lesions Compared to Paired Random Aspirates

Background:Bone disease is the most frequent clinical manifestation of multiple myeloma. In this prospective study we ask whether osteolytic lesions (OL) are driven by myeloma cells showing a different background of genetic alterations in terms of chromosomal aberrations and expressed single nucleotide variants (SNVs) compared to random aspirates (RA) from diffuse myeloma cell infiltration at the iliac crest (spatial genetic heterogeneity).Material and Methods:Consecutive sample-pairs (n=41) were prospectively obtained by CT-guided biopsies of OLs as well as simultaneous random bone marrow aspirates of the iliac crest, the latter undergoing CD138-purification of myeloma cells, in transplant eligible patients with previously untreated symptomatic multiple myeloma, after written informed consent. Peripheral blood mononuclear cells were used as germline control. Plasma cell infiltration in biopsies was quantified histologically. Samples pairs (n=8) were subjected to RNA-sequencing (Illumina HiSeq2000), gene expression profiling using DNA-microarrays (Affymetrix U133 2.0), whole exome sequencing (Illumina NextSeq 500), and arrayCGH (Affymetrix cytoscan array).Results and Discussion:Expressed single nucleotide variants.The spectrum of mutated genes in our samples comprises two of the most frequently mutated in symptomatic myeloma, i.e. KRAS and FAM46C, alongside those implicated in myeloma pathophysiology, e.g. mutations in IRF4, FGFR3, and CD200. In total, 1-10 clonal expressed non-synonymous SNVs were exclusively found in OL compared to RA, comprising e.g. WHSC1, FAM46C, and ROCK1P1. In 2/8 patients (25%), no expressed clonal differences between RA and OL were present.Single nucleotide variants.In investigated samples, 77-1569 non-synonymous SNVs appear with an allele frequency of ≥10% in OL and RA, clustering in 4-5 groups. The clonal constitution can vary, but subclones are detectable in both. Subclonal complexity is maintained (subclones remain present) in OL compared to RA, and the vast majority of subclonal changes is present in both, especially for expressed non-synonymous SNVs, incompatible with an "osteolytic clonal variant" driving OL in the majority of patients.Copy number alterations and loss of heterozygosity.Subtle differences in copy number between OL and RA are present. However, only 1/8 patients (12.5%) showed further "gained" aberrations in OL compared to RA, i.e. deletions on chromosome 7p, 8p, and 11p as well as 19p gain. Loss of heterozygosity was observed in 3/8 patients (37.5%) with a shared pattern between OL and RA in all of them.Conclusions:In our prospective study, the majority of alterations is shared between RA and OL. Spatial heterogeneity is present, but nature and frequency of alterations detectable exclusively in OL make them unlikely candidates in most myeloma patients for being causative for generation of OL. DisclosuresHillengass:Novartis: Research Funding; Sanofi: Research Funding; BMS: Honoraria; Celgene: Honoraria; Amgen: Consultancy, Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Goldschmidt:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Hose:EngMab: Research Funding; Takeda: Other: Travel grant; Sanofi: Research Funding.

Clinical characteristics and chemotherapy efficacy in patients with newly diagnosed multiple myeloma: observation of 176 cases

Objective To investigate the clinical characteristics and treatment efficacy in newly diagnosed multiple myeloma (MM). Methods The clinical data and treatment methods of 176 patients with newly diagnosed MM were retrospectively analyzed. Results The most common chief complaint in the patients with MM was bone pain. 26.1% (46/176) patients once experienced misdiagnosis. The overall response rate (ORR) was 65.9% (116/176), the ORR of bortezomib group (81.0%, 34/42) was significantly higher than that of M2 regimen group (61.8%, 34/55) and VAD regimen group(60.8%, 48/79) (P 0.05). The most common adverse reactions included hematologic toxicity, infection and peripheral neurotoxicity. Multiple organ failure was the main cause of death (47.1%, 16/34). Conclusions The clinical manifestations of MM are complex and diverse, which is easy to be misdiagnosed. Molecular genetic abnormalities are closely related to prognosis. Proteasome inhibitor bortezomib can improve the curative effect and not be affected by renal function. To prolong the survival time of the patients needs to prevent and control the infection and renal insufficiency actively. Key words: Multiple myeloma; Clinical characteristics; Treatment outcome

Secondary lymphoblastic leukemia occurring 38 months after the primary diagnosis of multiple myeloma: A case report.

Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by the accumulation of plasma cells in the bone marrow, the subsequent destruction of bone and organ dysfunction. The present study describes the case of a 66-year-old male patient who presented with the typical clinical manifestations of MM. The patient was administered a bortezomib and dexamethasone regimen for 2 cycles and achieved complete remission. Lenalidomide, vincristine, pirarubicin, dexamethasone, melphalan and thalidomide was used successively in consolidation therapy and maintenance therapy. The patient developed secondary B-cell lymphoblastic leukemia 38 months after the primary MM diagnosis was made. Owing to the exposure of the patient to a variety of therapeutic agents, it could be inferred that multiple immune defects may have played an important role in the secondary lymphoblastic leukemia of the patient. Microscopic examination and flow cytometry detection were important in identifying the secondary malignancy in this MM case.

Simvastatin Protects Osteoblasts from the Deleterious Effects of the Liquid Milieu of Multiple Myeloma.

Lytic bone lesions are the main clinical manifestation of multiple myeloma. The intense variety in this cell microenvironment, composed mainly of fibroblasts, osteoblasts, osteoclasts, immune cells and mesenchymal cells, is influenced by the massive presence of neoplastic plasma cells. Studies with statins have reported their action in stimulating the formation and reducing bone resorption. The aim of this study was to verify the in vitro response of human osteoblasts exposed to the supernatant (liquid milieu) of multiple myeloma. The data obtained indicate that simvastatin has positive effects on the growth of osteoblasts and protection against the anti-proliferative effects of multiple myeloma supernatant.