Staging System For Multiple Myeloma Research Articles

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

Evaluation of Residual Minimum Response with Free Serum Light Chains in Patients with Multiple Myeloma Diagnosis

The International Myeloma Group has added the serum free light chain assay to the multiple myeloma response criteria, incorporating a new category of response: the strict complete response. This response requires, in addition to the negativization of immunofixation and the absence of clonal CPs in the bone marrow, the normalization of the free κ / λ ratio. This is a descriptive study with the main objective of identifying patients who were diagnosed at the National institute of cancerology and were able to characterize their response. We included 67 patients with thalidomide Dexamethasone-based regimens up to 72.5% and 27.5% regimens based on others Types of drugs,The chemotherapy regímens were 2 patients chemotherapy with VAD (vincristine, Dexamethasone and doxorubicin), 2 patients melphalan prednisone, patients CyborD (cyclophosphamide, bortezomib and Dexamethasone, and Tacydex (thalidomide, dexamethasone and cyclophosphamide), two patients had carfilzomib based régimen and one patient received daratumumab. 21 patients were transplanted hematopoietic cells 90% had autologous transplantation and 10% were transplanted in tandem with an average of 4 months between infusions of hematopoietic progenitors. After the exposure to the first line of treatment, the response was assessed in the total population at 3 months. We obtained clinical and laboratory reports available in the medical history to be able to classify the response according to current criteria, 48.3% achieved partial response and only 3 patients obtained complete response. The rest of the patients were protocolized for autologous transplantation The new response was evaluated at 6 months of treatment, reaching complete responses up to 33.8%. At 9 months a complete response was documented in 19.3%. Finally, at 12 months, most of the complete responses are reached up to 37% Information on the serum light chain ratio was obtained in 76% of patients included in the sample. Finding up to 93% patients with MM RCe. In our center, only 4 patients, the 7% of the total of the analyzed sample, presented a ratio of free light chains in abnormal serum. In all cases of abnormal quotient, this was above the upper limit, reflecting a relative overproduction of free kappa chains. Follow-up was achieved in twelve patients whose response was reached in the first 3 to 6 months, remaining with a negative light chain ratio Regarding the time in which the strict response was reached, 96.77% of the patients presented a complete response at 3 months and the serum light chain ratio was negativized. However, only 23.71% of the patients presented a response that presented complete response to 12 months were able to negativize the ratio of serum light chains. With a 95% confidence interval and a standard error of estimation of (2.24-6.09%) implying that the further the timeline advances, the lower the probability of negative light chain response. Male and female gender presented negative response at 3 and 9 months respectively. As for gender, there were no significant changes, 67% of the women had a strict complete response in the first 6 months, while 62% of the men had a complete complete response. With a 95% confidence interval and a standard error of estimation (2.90-8.40%) for the masculine gender and (3.51-8.68%) for the feminine gender. Finally, in comparison with the international staging system for multiple myeloma for patients who managed to respond to the first 3 months, 96.67% belonged to the ISS and 68% of the patients who presented a response at 6 months belonged to the ISS II group. 55.93% achieved complete complete responses at 12 months belonging to the ISS III group. With a 95% confidence interval and a standard error of estimation of ISS I (11.59-12.35%) for ISS II (3.28-9.38%) for ISS I, And (6.05-9.76%) for ISS III. During the last decade there have been important changes in the treatment of multiple myeloma that have resulted in an improvement in prognosis. Nowadays, we know that the inclusion of proteasome inhibitors as well as new agents and some low availability monoclonal antibodies in our medium have a profile that may be of future utility in these patients. As is well known, RC is rarely achieved with the use of conventional chemotherapy. This population, although the majority deal with the institutional scheme obtained extremely encouraging responses since more than half of those who achieved the complete response achieved the stricte complete response. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evolving Concepts in the Diagnosis and Staging of Multiple Myeloma

Until recently, treatment for multiple myeloma was only initiated in symptomatic disease. Greater understanding of the underlying biology and the development of new biomarkers, however, has led to changes in diagnosis, and with the help of improved imaging techniques, clinicians are increasingly identifying patients with early myeloma who may benefit from treatment. One major development in diagnostic imaging is the replacement of radiography with CT. PET/CT imaging is also useful for treatment response assessment, because the disappearance of focal lesions is an important prognostic factor. Finally, the Revised International Staging System for multiple myeloma has incorporated additional prognostic markers of aggressive disease, and risk-adapted treatment has been shown to improve survival.

Cytogenetic Changes in Multiple Myeloma Timeline: A Tertiary Center's Experience

Introduction Risk stratification in Multiple Myeloma according to cytogenetic abnormalities has been utilized clinically to guide understanding of prognosis. Specific cytogenetics abnormalities such as deletion 17p, t(14,16) and t(4,14) have been associated with more aggressive disease and poor outcome[1]. It has been postulated that genetic aberrations evolve in a temporal pattern in non-hyperploid multiple myeloma such that 13q deletion and t14q32 tend to be early events while chromosome 1 and 17 abnormalities occur as later events [2]. Furthermore, other studies have suggested higher frequencies of high risk cytogenetic abnormalities (such as deletion 17p and gain of 1q) at relapse after upfront autologous stem cell transplant [3]. Our study examined the cytogenetic profile of patients treated at a tertiary health system at the time of diagnosis and at first relapse, irrespective of bone marrow transplant and treatment Methods This is a retrospective study of patients treated at Henry Ford Cancer Institute/Henry Ford Health System. Subjects were adults diagnosed with multiple myeloma with relapse confirmed by a bone marrow biopsy between January 2014 and January 2019. The cytogenetic profile at time of diagnosis and relapse for each patient was reviewed. Exclusion criteria included history or current diagnosis of another malignancy. 145 cases were identified, of which 112 cases were excluded: 19 cases with plasmacytoma but no bone marrow relapse, 32 with other malignancy, 21 with relapse before study period, 5 with relapse after study period, and 35 with bone marrow biopsy or cytogenetics not available for review. As such, we analyzed the remaining 33 cases Results 26 of the 33 cases underwent a bone marrow transplant. A third of the patients (11) developed new mutations, which included 17p deletion (3), 13q deletion (1), chromosome 1 abnormality (1), new trisomies (5), t(11,14) (4), hypoploidy (1), and IgH/CCDN1 changes (1). Conclusion Though cytogenetic evolution in multiple myeloma has been studied, not all patients undergo a bone marrow biopsy and cytogenetic evaluation at relapse, which limits this assessment. Despite our sample size being limited as a majority of the study population did not have cytogenetics recorded at relapse, our study reveals that new mutations can arise in a significant proportion of patients at relapse, some of which are known to be associated with poor prognosis. This can be potentially prognostic, as presence of new high-risk mutations could alter the presumed disease trajectory, and these could also have therapeutic consequences. While further studies with a larger sample size are needed to determine the frequencies of each mutation, our study underscores the importance of dedicated monitoring of cytogenetics at each relapse in multiple myeloma. References Palumbo, A., et al., Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol, 2015. 33(26): p. 2863-9. Jimenez-Zepeda, V.H., E. Braggio, and R. Fonseca, Dissecting karyotypic patterns in non-hyperdiploid multiple myeloma: an overview on the karyotypic evolution. Clin Lymphoma Myeloma Leuk, 2013. 13(5): p. 552-8. Merz, M., et al., Longitudinal fluorescence. Haematologica, 2017. 102(8): p. 1432-1438. Disclosures No relevant conflicts of interest to declare.

Validation and Improvement Opportunities of the Revised International Staging System for Multiple Myeloma: An Analysis on Mature Data from European Clinical Trials within the Harmony Big Data Platform

Validation and Improvement Opportunities of the Revised International Staging System for Multiple Myeloma: An Analysis on Mature Data from European Clinical Trials within the Harmony Big Data Platform

Modified risk stratification (MRS) for Multiple Myeloma- A simplified model using machine learning

Risk stratification provides an important clue that helps clinicians decide differential medical treatment. The staging system for multiple myeloma (MM) has evolved with advancement of treatment protocols, from Salmon Durie staging to International Staging System (ISS) to Revised-ISS (R-ISS). The R-ISS is based on serum levels of albumin (alb), β2 microglobulin (β2m), lactate dehydrogenase (LDH) and cytogenetic aberrations using fluorescent in-situ hybridization (FISH). Because of limited availability of FISH-based testing, R-ISS for MM has not been applied widely in most developing countries.

CD38 in Adenosinergic Pathways and Metabolic Re-programming in Human Multiple Myeloma Cells: In-tandem Insights From Basic Science to Therapy.

Tumor microenvironments are rich in extracellular nucleotides that can be metabolized by ectoenzymes to produce adenosine, a nucleoside involved in controlling immune responses. Multiple myeloma, a plasma cell malignancy developed within a bone marrow niche, exploits adenosinergic pathways to customize the immune homeostasis of the tumor. CD38, a multifunctional protein that acts as both receptor and ectoenzyme, is overexpressed at all stages of myeloma. At neutral and acidic pH, CD38 catalyzes the extracellular conversion of NAD+ to regulators of calcium signaling. The initial disassembly of NAD+ is also followed by adenosinergic activity, if CD38 is operating in the presence of CD203a and CD73 nucleotidases. cAMP extruded from tumor cells provides another substrate for metabolizing nucleotidases to signaling adenosine. These pathways flank or bypass the canonical adenosinergic pathway subjected to the conversion of ATP by CD39. All of the adenosinergic networks can be hijacked by the tumor, thus controlling the homeostatic reprogramming of the myeloma in the bone marrow. In this context, adenosine assumes the role of a local hormone: cell metabolism is adjusted via low- or high-affinity purinergic receptors expressed by immune and bone cells as well as by tumor cells. The result is immunosuppression, which contributes to the failure of immune surveillance in cancer. A similar metabolic strategy silences immune effectors during the progression of indolent gammopathies to symptomatic overt multiple myeloma disease. Plasma from myeloma aspirates contains elevated levels of adenosine resulting from interactions between myeloma and other cells lining the niche and adenosine concentrations are known to increase as the disease progresses. This is statistically reflected in the International Staging System for multiple myeloma. Along with the ability to deplete CD38+ malignant plasma cell populations which has led to their widespread therapeutic use, anti-CD38 antibodies are involved in the polarization and release of microvesicles characterized by the expression of multiple adenosine-producing molecules. These adenosinergic pathways provide new immune checkpoints for improving immunotherapy protocols by helping to restore the depressed immune response.

Next Generation Sequencing-based Validation of the Revised International Staging System for Multiple Myeloma: An Analysis of the MMRF CoMMpass Study

IntroductionThe clinical application of the Revised International Staging System (R-ISS) for multiple myeloma may be limited by heterogeneity in clinical interphase fluorescent in situ hybridization (FISH) practices for detecting chromosomal abnormalities (CAs). Next generation sequencing (NGS)-based FISH (Seq-FISH) has demonstrated improved sensitivity and similar specificity relative to clinical FISH, and provides a standardized, single-pass method for identifying high-risk CAs. To date, calculating R-ISS stage using Seq-FISH (R-ISS-NGS) has not been validated. Patients and MethodsWe identified 672 patients with sufficient data to calculate R-ISS-NGS from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study. R-ISS-NGS was calculated from original ISS stage, lactate dehydrogenase, and CAs detected by Seq-FISH. Endpoints included overall survival and progression-free survival. We conducted multivariate analyses controlling for age and gender in order to compare outcomes across stages I to III of both the original ISS and R-ISS-NGS. ResultsThe median follow-up was 24 months. The R-ISS-NGS resulted in significant redistribution of patients into stage II, relative to the original ISS. With respect to stage I, R-ISS-NGS stages II and III of were associated with worse progression-free survival or overall survival, more so than the staging schema of the ISS, thus validating the use of Seq-FISH in staging. ConclusionUsing CAs detected by Seq-FISH and data from the CoMMpass study, we validated the R-ISS with a large, generalizable cohort. This study validates the substitution of Seq-FISH for clinical FISH, especially in large registry studies. Additionally, use of the validated R-ISS-NGS will strengthen outcomes research generated from the CoMMpass study.

High Risk Multiple Myeloma: Better Outcomes with Upfront Tandem Autologous- Non-Myelo Ablative Allogeneic Stem Cell Transplantation Compared to Upfront Autologous Stem Cell Transplantation

Aim/Background: The outcomes of high risk multiple myeloma (HR-MM) remain poor. As per the revised international staging system (R-ISS), high risk patients, defined by International Staging System (ISS) stage 3 plus high risk chromosomal abnormality and/or high Lactate Dehydrogenase (LDH), have particularly poor outcomes with 5 year progression free survival (PFS) and overall survival (OS) of 24% and 40% respectively.1 Tandem autologous - non-myeloablative allogeneic stem cell transplantation (ASCT-NMA AlloSCT), when used as upfront consolidation may improve the outcome via a graft versus myeloma effect. We performed a retrospective analysis comparing patients who had upfront tandem ASCT-NMA allo SCT for HR-MM with a HR-MM control group who were conventionally treated with upfront ASCT alone.Method: From May 2008 to June 2015, 29 HR-MM patients were treated at the Alfred Hospital Melbourne, with upfront tandem ASCT-NMA alloSCT. HR-MM was defined by the presence of at least 2 of 5 high risk features including International Staging System (ISS) score III, adverse cytogenetics [t(4;14 and/or 17p- identified on FISH and/or complex karyotype on metaphase analysis], elevated lactate dehydrogenase (LDH), plasma cell leukemia (all at diagnosis) or induction failure (less than partial remission (PR)) with proteosome inhibitor (PI) or immunomodulator (IMID) based combination chemotherapy. Outcomes for these patients were compared with 12 HR-MM patients contemporaneously treated at the Royal Adelaide hospital, Adelaide with upfront ASCT alone. All ASCT were conditioned with melphalan 200mg/m2; NMA were conditioned with oral fludarabine 48mg/m2 on days -4 to -2 and 2Gy TBI on day 0. All tandem ASCT-NMA allo SCT patients received cyclosporine and mycophenylate mofetil for graft versus host disease prophylaxis.Results: Median age of the tandem cohort was 52 years (range: 22-66 years) whereas the ASCT cohort was older with a median age of 59 years (range: 51-72 years; p=0.01). 44.8% of the tandem group and 50% of the ASCT group were male (p=0.77). 18 patients (62.1%) of the tandem cohort were transplanted from unrelated donors. Within the tandem cohort 24.1% developed grade II-IV acute graft versus host disease (GVHD) and 44.8% had extensive chronic GVHD. After a median follow up of 48.9 months, progression free survival (PFS) was significantly superior for tandem group compared to ASCT group (median PFS=1166 days versus 399 days; p=0.001) (Fig:1). The 3-year cumulative incidence of relapse was 31.9% for tandem group against 79.8% for ASCT group (p=0.005). The 5-year overall survival of tandem and ASCT groups were 59.84% and 44.56%, respectively (p=0.38). Transplant related mortality was not significantly different between the groups (20.7% for tandem group and 8.3% for ASCT group; p=0.32). To avoid any age bias, we then compared the ASCT cohort with an older subgroup of the tandem cohort (17 patients with a median age of 58 years, range: 51-66 years, p=0.61 when compared with ASCT cohort) and demonstrated that the PFS was still significantly superior for the tandem approach (median PFS=1179 days for tandem cohort versus 399 days for ASCT cohort; p=0.009). Minimal residual disease (MRD) analysis by 8-colour Euroflow (sensitivity at 10-5) was negative in 12 of 17 tandem patients tested.Conclusion: Upfront tandem ASCT-NMA AlloSCT for HR-MM results in superior PFS and an emerging OS benefit with acceptable toxicity when compared to conventional ASCT. High-resolution MRD negativity in a significant proportion of tandem patients predicts for extended disease free survival.Ref:1. Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015 Sep 10;33(26):2863-69. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Updated Diagnostic Criteria and Staging System for Multiple Myeloma.

There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advances have necessitated a revision of the disease definition and staging of MM. Until recently, MM was defined by the presence of end-organ damage, specifically hypercalcemia, renal failure, anemia, and bone lesions (CRAB features) that can be attributed to the clonal process. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria for MM to add three specific biomarkers that can be used to diagnose the disease in patients who did not have CRAB features: clonal bone marrow plasma cells greater than or equal to 60%, serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/L or higher, or more than one focal lesion on MRI. In addition, the definition was revised to allow CT and PET-CT to diagnose MM bone disease. These changes enable early diagnosis and allow the initiation of effective therapy to prevent the development of end-organ damage for patients who are at the highest risk. A new staging system has been developed that incorporates high-risk cytogenetic abnormalities in addition to standard laboratory markers of prognosis.

Updated Diagnostic Criteria and Staging System for Multiple Myeloma

There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advanc...

The Association of International Staging System (ISS) Stage with Disease and Symptom Burden in Patients with Newly Diagnosed Multiple Myeloma

Background: The clinical presentation of multiple myeloma (MM) varies greatly but often includes bone pain, anemia, renal dysfunction, hypercalcaemia, and/or constitutional symptoms. There are no signs or symptoms that are disease specific. The earliest staging system for MM, the Durie-Salmon (DS), associated disease and symptom burden with prognosis; however, it has been largely replaced by the International Staging System (ISS), which is easier to compute and better identifies patients with the poorest prognosis. It is unclear if ISS stage, like DS, is associated with disease or symptom burden.Objective: To compare disease and symptom burden of patients with newly diagnosed MM by ISS Stage.Methods: Data was extracted from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway corresponding with interim analysis 6 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data and patient reported quality of life (EORTC QLQ-C30 and QLQ-MY20), as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator and/or a proteasome inhibitor for initial MM treatment; and no prior malignancies in the past 5 years.All clinical data was reported by trained data analysts at the enrolling center with the exception of flow cytometry which was performed centrally; raw lab values for beta-2 microglobulin and albumin were entered and stage was subsequently calculated by the analysts for this study according to the ISS (Greipp et al, JCO 2005). Twenty-six patients with unknown ISS were excluded from the analysis. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with one-way ANOVA tests.Results: 599 patients were eligible for analysis. Sex, race, and heavy and light chain isotypes were all evenly distributed among the ISS stages; however, median age for ISS stage III was 67, 65 for stage II and 62 for stage I (p<0.001). Stage I and II patients were similar in disease burden, but stage III patients had higher serum M-proteins (p<0.001), LDH (p=0.002), bone marrow plasma cells (p<0.001), circulating plasma cells (p<0.001), and creatinine (p<0.001), and lower hemoglobin (p<0.001) and platelets (p=0.001). Further, stage III patients had poorer performance status (p<0.001), global health (p<0.001), physical functioning (p<0.001), social functioning (p<0.001), and role functioning (p<0.001), and increased fatigue (p<0.001) and pain (p=0.016). Results are summarized in Table 1.Conclusions: Stage III had a higher disease and symptom burden than stage I and II patients. Stage I and II patients were similar in most measures suggesting that ISS may not discriminate between these groups well, this is supported by other studies that have failed to find outcomes differences between stage I and II patients.Table 1Stage I n= 204Stage II n = 210Stage IIIn = 185pDemographicsAge in years626567<0.001Male64%57%62%NSRaceNSWhite80%83%74%Black19%13%23%Other2%3%3%Heavy ChainNSIgG80%80%75%IgA20%20%25%Light ChainNSKappa65%61%60%Lambda34%38%38%Biclonal1%2%2%Disease BurdenSerum M-Protein g/dL1.92.03.2<0.001LDH μkat/L2.72.83.00.002Bone Marrow Plasma Cells*7%9%13%<0.001Circulating Plasma Cells*0%0%0.1%<0.001Calcium mmol/L2.42.32.4<0.001Creatinine μmol/L8288149<0.001Hgb mmol/L7.46.45.8<0.001Platelets x109/L222212199.001Bone Lesions61%52%53%NSSymptom Burden/Quality of Life MeasuresECOG Performance Status<0.001047%42%22%149%42%54%25%8%15%3-40%8%9%Global Health Scale666650<0.001Physical Functioning Scale868063<0.001Cognitive Functioning Scale838383NSEmotional Functioning Scale757575NSSocial Functioning Scale838366<0.001Role Functioning Scale666650<0.001Disease Symptom Scale272227NSFatigue Scale333344<0.001Pain Scale3333420.016Note-Median presented unless specified.*- CD38+/CD138+ by flow cytometry DisclosuresVij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy.

Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group.

The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.

Understanding multiple myeloma

Understanding multiple myeloma

Antigen Expression Patterns of Plasma Cell Myeloma: An Association of Cytogenetic Abnormality and International Staging System (ISS) for Myeloma.

Immunophenotyping of plasma cell has become an important diagnostic tool for plasma cell myeloma. There have been a few studies for association of antigen expression and cytogenetic abnormality of plasma cell myeloma. A total of 68 symptomatic/smoldering plasma cell myeloma case were analyzed by multicolor flow cytometry using CD38 and CD138 for primary gating of plasma cells. A conventional cytogenetics and fluorescence in situ hybridization (FISH) studies for detection of del(13q) or aneuploidy, del(17p), and IGH/FGFR translocation were done. We statistically analyzed the association of antigen expression and cytogenetic abnormality/myeloma stage (international staging system for multiple myeloma). Positive expression of CD19, CD28, CD45, CD56, CD117, and CD274 was detected in 8.8%, 50.0%, 50.0%, 75.0%, 39.7%, and 2.9% of cases, respectively. CD117-negative cases were associated with hypodiploidy (P = 0.017). CD45-negative cases were associated with deletion 13 or aneuploidy (P < 0.001) and del(17p)(P = 0.011) by FISH. CD45-negativity or CD117-negativity was associated with advanced stage (P = 0.012 and P = 0.016, respectively). The antigen expression patterns of myeloma plasma cell were associated with cytogenetic abnormality and stage.

Multiple myeloma: a review

Abstract Multiple myeloma is an incurable malignant tumour of plasma cells of the bone marrow and is the most common primary neoplasm arising in bone. Most patients have disseminated disease and a poor prognosis. Orthopaedic and spinal surgeons are likely to be exposed to such patients, as myeloma forms a common differential amongst osteolytic lesions after the 5th decade. Myeloma leads to variable renal impairment, anaemia, hypercalcaemia, infection and pathological fractures. Osteolytic lesions, generalised bone loss and elevated bone turnover precipitate pathologic fractures due to complex interactions between bone marrow stromal cells, osteoblasts, osteoclasts and myeloma cells within the bone marrow microenvironment. Survival rates vary greatly; mean five and 10-year survival rates are estimated to be 68% and 55% respectively. The International Staging System for multiple myeloma defines three risk categories, as determined by the serum concentration of β2-microglobulin and albumin. Cytogenetic testing for specific mutations can identify patients at particularly high risk of morbidity and mortality. Management includes the use of chemotherapy, radiotherapy, haemopoietic stem cell transplant and bisphosphonates. Surgical intervention is indicated for (impending) pathological fractures and to decompress and stabilise spinal cord compression. Orthopaedic surgeons must be aware of the pathoaetiology and disease-related complications in multiple myeloma patients who may require urgent surgical intervention.

Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

These Clinical Practice Guidelines are endorsed by the Japanese Society of Medical Oncology (JSMO) incidence and epidemiology Multiple myeloma (MM) accounts for 1% of all cancers and ∼10% of all haematological malignancies. The incidence in Europe is 4.5–6.0/100 000/year with a median age at diagnosis of between 65 and 70 years; the mortality is 4.1/100 000/year. Almost all patients with MM evolve from an asymptomatic pre-malignant stage termed monoclonal gammopathy of undetermined significance (MGUS). MGUS progresses to MM at a rate of 1% per year. In some patients, an intermediate asymptomatic but more advanced pre-malignant stage termed smouldering (or indolent) multiple myeloma (SMM) can be recognised. SMM progresses to myeloma at a rate of 10% per year over the first 5 years following diagnosis, 3% per year over the following 5 years and 1.5% per year thereafter [1]. diagnosis Diagnosis of MM should be based on the following tests: [1] -Detection and evaluation of the monoclonal (M-) component by serum and/or urine protein electrophoresis (concentrate of 24 h urine collection); nephelometric quantification of IgG, IgA and IgM immunoglobulins; characterisation of the heavy and light chains by immunofixation; and serum-free light-chain (FLC) measurement; -Evaluation of bone marrow (BM) plasma cell infiltration: BM aspiration and/or biopsies are the standard options to evaluate the number and characteristics. Moreover, the BM sample should be used for cytogenetic/fluorescence in situ hybridization (FISH) studies and also has the potential for immunophenotypic and molecular investigations; -Evaluation of lytic bone lesions: a radiological skeletal bone survey, including spine, pelvis, skull, humeri and femurs is necessary. A magnetic resonance imaging (MRI) or computed tomography (CT) scan may be needed to evaluate symptomatic bony sites, even if the skeletal survey is negative and the patient has symptoms suggesting bone lesions. Moreover, MRI provides greater detail and is recommended whenever spinal cord compression is suspected. Fluorodeoxyglucose positron emission tomography is currently under evaluation but should not be systematically used; -Complete blood cell count, with differential serum creatinine and calcium level.

Chronic kidney disease stage 5 as the prognostic complement of International Staging System for multiple myeloma

Reversal of renal impairment (RI) in patients with multiple myeloma (MM) has been evaluated using the estimated glomerular filtration rate (eGFR(MDRD) ) formula developed by the Modification of Diet in Renal Disease study group. However, the prognostic impact of eGFR(MDRD) at diagnosis of MM is not well studied, particularly its use in conjunction with the International Staging System (ISS). Newly diagnosed patients with MM were enrolled between 1996 and 2007. Data on clinical features, laboratory tests, and overall survival were compared in terms of corresponding eGFR(MDRD). A total of 387 patients with MM (median age, 71 yr) were enrolled. At diagnosis, 56% had ISS stage III disease; the median values of serum creatinine (SCr) and eGFR(MDRD) were 1.4 mg/dL and 38.2 mL/min/1.73 m(2) , respectively. Thirty-four percent of patients had SCr of ≥ 2.0 mg/dL, and 81.2% had chronic kidney disease stages 3-5 (CKD 3-5). Higher CKD stages were significantly more common in men, older patients (≥ 65 yr), and those with Durie-Salmon and ISS stage III, light-chain diseases, anemia, thrombocytopenia, hypercalcemia, elevated serum β(2) microglobulin, or lactate dehydrogenase. In the Cox regression model, CKD 4-5 or CKD 5 alone was independently associated with poor survival. A diagnosis of CKD 5 was shown to be useful in identifying the subgroup of ISS-III patients at high risk - those with a median overall survival of 7.2 months. Our study demonstrates the prognostic impact of eGFR(MDRD) in patients with MM and CKD 5 as the ISS-independent surrogate predictor of poorest prognosis.

Free Light Chains of Immunoglobulin as a Prognostic Factor for Some Plasmaproliferative Diseases

Free Light Chains of Immunoglobulin as a Prognostic Factor for Some Plasmaproliferative DiseasesQuantitation of monoclonal immunoglobulins and their fragments is used for monitoring the plasmaproliferative disease course and the effect of therapy. The aim of free light chains examination was to evaluate the significance of the FLC ratio as a prognostic factor for remission, progression and survival in different disease groups. The concentrations of immunoglobulins and free light chains were measured by an immunonephelometric method on a »SIEMENS« DADE BN II analyser with reagents (Freelite, The Binding Site, UK). In this examination 151 patients from 3 different disease groups: 1. Light chain disease or Bence Jones myeloma (37), 2. Biclonal gammopathy with FLC (23) and 3. Monoclonal gammopathy of undetermined significance (91), were investigated during a period of 7 years. The reference interval for FLC ratio is 0.26-1.65. According to the International Staging System for multiple myeloma, a serum FLC ratio of &lt;0.03 or &gt;32 was taken as abnormal. The patients with light chain disease and biclonal gammopathy with FLC with an abnormal FLC ratio and a combination of adverse risk factors (76.7%) had median survival times of 22-30 months, versus patients with a normal or slightly varied FLC ratio without adverse risk factors (23.3%) with median survival times of 39-51 months. About 38% of patients who had shown lowered free light chains values by more than 50% under therapy, achieved disease remission in the light chain disease and biclonal gammopathy with FLC groups. In the group of patients with monoclonal gammopathy of undetermined significance, 66.0% had a normal or slightly modified FLC ratio which corresponds to low and low-intermediate risk of disease progression, as opposed to 34.0% with an abnormal FLC ratio (&lt;0.25 or &gt;4) which corresponds to high and high-intermediate risk. An abnormal FLC ratio in the examined groups could be an independent risk factor for progression and poorer disease prognosis.

Artifactual measurement of low serum HDL-cholesterol due to paraproteinemia

Artifactual measurement of low serum HDL-cholesterol due to paraproteinemia