Recurrence Of Multiple Myeloma Research Articles

Predictive Value Analysis of Serum Ig A, Ig G, and TNF-α in Recurrence of Multiple Myeloma.

Objective The study is aimed at analyzing the predictive value of serum Ig A, Ig G, and TNF-α in the recurrence of multiple myeloma (MM). Methods 136 patients with MM treated in our hospital from January 2010 to January 2017 were followed up for 5 years. Finally, 100 patients who met the inclusion and exclusion criteria and had the complete follow-up visit were selected as the study subjects, with the recurrence of MM as endpoint event, and the observation was taken until the occurrence of endpoint event in patients or the termination of this study. They were divided into the recurrence group (RG) and the nonrecurrence group (NRG) according to whether the endpoint event occurred. The venous blood of patients was collected at the first diagnosis and subsequent visit (at the time of recurrence or termination of the study) to measure the Ig A and Ig G using a full automatic special protein analyzer and the TNF-α level by enzyme-linked immunosorbent assay. The data obtained in this study were analyzed by univariate analysis to choose the factors with difference in statistical significance to draw the ROC curve, and the areas under the curve (AUC) were recorded to analyze the potential mechanism of Ig A, Ig G, and TNF-α in predicting the recurrence of MM. Results After follow-up visit, there were 62 patients with recurrence (62.0%) and 38 patients without recurrence (38.0%), with no obvious difference in gender, age, body weight, and immune classification between the two groups (P > 0.05). Compared with the NRG, the levels of soluble interleukin-2 receptor (sIL-2R) and β2-microglobulin (β2-MG) in the RG at the first diagnosis were distinctly higher (P < 0.001); the levels of Ig A, Ig G, and TNF-α in the RG at the first diagnosis were visibly higher (P < 0.05); and the levels of Ig A, Ig G, and TNF-α in the RG at the subsequent visit were clearly higher (P < 0.05). There was a correlation between Ig G, Ig A, and TNF-α and β2-MG at the first diagnosis and the subsequent visit (P < 0.05); there was a correlation between Ig G and TNF-α, and sIL-2R at the first diagnosis and the subsequent visit (P < 0.05); and there was a correlation between Ig A and sIL-2R at the subsequent visit (P < 0.05). The AUC of Ig G, Ig A, and TNF-α in predicting the MM at the first diagnosis were 0.772, 0.776, and 0.778, respectively. Conclusion The serum Ig A, Ig G, and TNF-α had a predictive value in the recurrence of MM, and TNF-α was correlated with sIL-2R and β2-MG, with the highest AUC and the best predictive value.

Prognostic significance of 68Ga-Pentixafor PET/CT in multiple myeloma recurrence: a comparison to 18F-FDG PET/CT and laboratory results.

This study investigates the prognostic value of 68Ga-Pentixafor PET/CT using PET-derived quantitative in multiple myeloma (MM) patients with suspected recurrence in comparison to 18F-FDG PET/CT and clinical data. Twenty-four MM patients with suspicion for relapse who underwent 68Ga-Pentixafor and 18F-FDG PET/CT were retrospectively evaluated. Total bone marrow glycolysis for 18F-FDG (TBMFDG) and total bone marrow uptake for 68Ga-Pentixafor PET/CT (TBMCXCR4) were calculated using whole-body metabolic tumor burden obtained by dedicated software (MIM 7.0.6). The patients were followed for 19-24months, and the association of PET-derived quantitative data with overall survival (OS) was analyzed. 68Ga-Pentixafor PET/CT was positive in 17 patients, of which 13 were also positive on 18F-FDG PET/CT, whereas 7 patients were negative on both scans. The positive rate of 68Ga-Pentixafor and 18F-FDG PET/CT on a patient-based approach was 70.8% and 54.1%, respectively. 68Ga-Pentixafor positivity was significantly associated with OS (p = 0.009), and 18F-FDG positivity was at the margin of statistical significance (p = 0.056). TBMCXCR4 and TBMFDG were negatively correlated with OS (r = -0.457, p = 0.025 and r = -0.617, p = 0.001, respectively). The OS was negatively correlated with beta-2-microglobulin levels (r = -0.511, p = 0.01) and CRAB score (r = -0.592, p = 0.002) as an indicator of the end-organ disease, which confirmed these results. Serum beta-2-microglobulin levels and CRAB score were also correlated with TBMCXCR4 (r = 0.442, p = 0.039 and r = 0.573, p = 0.003, respectively) and TBMFDG (r = 0.543, p = 0.009 and r = -0.424, p = 0.003, respectively). 68Ga-Pentixafor PET/CT positivity is a negative prognostic factor in the survival outcome of MM patients. Complementary 68Ga-Pentixafor PET/CT has the potential to overcome 18F-FDG PET/CT limitations and helps a more precise risk stratification.

Isolated Leptomeningeal Recurrence of Multiple Myeloma.

Isolated Leptomeningeal Recurrence of Multiple Myeloma.

The Diagnosis and Treatment of Multiple Myeloma.

Multiple myeloma is a malignant disease of plasma cells with a worldwide incidence of 6-7 cases per 100 000 persons per year. It is among the 20 most common types of cancer in Germany. This review is based on pertinent publications up to December 2015 that were retrieved by a selective search of PubMed employing the terms "multiple myeloma" AND "therapy" OR "diagnostic." Systematic reviews, meta-analyses, randomized controlled trials, and treatment recommendations from Germany and abroad were considered. The diagnostic evaluation of multiple myeloma comprises thorough history-taking and physical examination, various laboratory tests including analysis of a 24-hour urine sample, a bone-marrow biopsy, and skeletal radiography. Systemic treatment should be administered only when organ damage has been diagnosed. The type of treatment to be given is chosen individually on the basis of the patient's age, comorbidities, and risk profile. High-dose therapy with autologous stem-cell transplantation remains the treatment of choice for patients under age 70 who are otherwise in good health. For patients who are not candidates for high-dose therapy or who have had a recurrence of multiple myeloma after prior high-dose therapy, there are a number of further conventional treatment options. Patients need not only systemic antineoplastic treatment, but also supportive treatment for the prevention of treatment-induced toxicity and myeloma-associated organ damage. Recent therapeutic advances have made the treatment of multiple myeloma both more complex and more costly. In particular, the median survival of patients with multiple myeloma has been markedly prolonged through the use of targeted drugs such as proteasome inhibitors and immune modulators.

Multiple Myeloma Recurrence with Optic Nerve Infiltration Diagnosed by Vitrectomy, Immunohistochemistry, and in Situ Hybridization

We present a case of multiple myeloma recurrence diagnosed by optic nerve infiltration. Interventional case report with clinical, surgical, immunohistochemical, and fluorescence in situ hybridization correlation. A 51-year-old woman with a history of bilateral invasive ductal breast carcinoma and multiple myeloma, both in remission on maintenance bortezomib, was referred for sudden, painless loss of vision OS. Examination demonstrated anterior vitritis with severe optic disc elevation, with yellow-white thickening, peripapillary hemorrhages, and a retinal detachment inferiorly. Diagnostic vitrectomy showed CD138-positive and BRST2-negative cells. Fluorescence in situ hybridization was positive for del(13q) and p53 deletion and negative for CCND1/IGH. This is the first report of optic nerve infiltration of multiple myeloma as evidence of recurrence while on maintenance chemotherapy. We demonstrate that diagnostic vitrectomy and immunohistochemistry of vitreous fluid is feasible for the diagnosis of recurrent multiple myeloma.

Incidental Discovery of a Testicular Plasmacytoma at Initial Presentation of Multiple Myeloma

Testicular plasmacytomas are a rare phenomenon reported in the literature and they can occur as a solitary plasmacytoma, as a recurrence of multiple myeloma, or concurrently in an active myeloma. We report the case of a 43-year-old man who presented with back pain and was diagnosed with multiple myeloma. A CT scan performed to determine the extent of disease revealed an incidental mass in the testicle. Immunohistochemical staining of the mass revealed monoclonal cytolpasmic IgA in the tumor cells and serum studies showed this same immunoglobulin. Following orchiectomy, radiotherapy to the vertebra, chemotherapy with bortezomib, dexamethasone, and doxorubicin, and an autologous bone marrow transplant, the patient is alive twelve months after diagnosis and is in complete remission.

Contrast enhanced MRI and 18F-FDG PET-CT in the assessment of multiple myeloma: A comparison of results in different phases of the disease

ObjectivesThe aim of our study was to compare the accuracy of contrast enhanced MRI and FDG PET-CT in the staging, treatment evaluation and follow-up of multiple myeloma. MethodsWe retrospectively reviewed 210 PET-CT and 210 MRI studies of patients affected by multiple myeloma. MRI was always performed within 15 days of PET-CT. All the images have been evaluated by two expert oncologic radiologists. ResultsPatient population included 81 females and 110 males (age 61.9±9.9 years-old). Sixty-two patients have been evaluated at diagnosis, 58 at the end of therapies and 90 during follow-up. In 12/62 patients (19.4%) at diagnosis, differences between MRI and PET-CT findings determined changes in the staging: PET-CT was responsible for 11 down-staging (17.7%) and MRI only for one (1.6%). In 27/40 patients (67.5%) with good or complete clinical response to therapies the normalization of findings was faster for PET-CT than MRI. Ten out of 90 patients (10/90 – 11.1%) in follow-up protocol presented clinical recurrence of the disease: MRI detected active lesions in 8 of them (80.0%) and PET-CT in 5 patients (50.0%, all detected by MRI too). ConclusionsMRI achieved better results than PET-CT in the staging and in patients with multiple myeloma recurrence. PET-CT, showed prompt change of imaging findings, faster than MRI, in patients with positive response to therapy.

Development of New Treatment Strategies Targeting Clonogenic and Tumorigenic Myeloma Side Population.

AbstractAbstract 1581 Introduction:Recurrence of multiple myeloma (MM) after establishment of complete remission indicates the presence of a small fraction of resistant tumor cells which persists after treatment and expresses stem cell-like characteristics.In our previous studies, we confirmed the existence of a MM population with “stem-like” features, known as side population (SP) cells. SP cells exhibit substantial heterogeneity not only in MM cell lines, but also in primary samples. Importantly, SP cells manifest significant clonogenic potential in vitro compared to the main population (MP). In our current study, we examined whether the clonogenicity of SP cells in vitro is associated with tumorigenic potential of SP cells in vivo. Methods and Results:To evaluate tumorigenicity of SP cells, several dilutions of sorted SP and MP cells were injected into immunocompromised mice. In CB17/SCID mice, sorted SP cells (range 105 - 106 cells/mouse) from OPM1 and KMS11 cell lines induced significantly greater tumor growth compared to MP cells (90-70% less tumor mass than SP tumors). At lower innocula of cells (10 × 103 cells/mouse), SP cells resulted in tumors, whereas no tumors were produced by MP cells. In NOD/SCID mice, lower numbers of SP cells (1 × 103 cells/mouse) produced tumor. These data strongly support the tumorigenic potential of SP sub-population and provide the rationale for targeting these cells in novel therapeutic strategies in MM.Indeed, our previous studies show that lenalidomide significantly decreased the percentage and clonogenicity of SP cells. We therefore expanded these studies to next examine whether other novel agents target SP cells. Novel agents pomalidomide (1 μM; decreased by 97%) and histone deacetylase (HDAC) inhibitor vorinostat (0.4 μM; decreased by 86%) significantly affected SP cells. Natural plant compound sulforaphane (2 μM; decreased by 86%), but not isothiocyanate PEITC, also decreased percentage of SP cells.We similarly evaluated the anti-SP effect of compounds known or proposed to target crucial signaling pathways in hematopoietic/cancer stem cells including cantharidin (terpenoid inhibitor of PPA2) and its demethylated analog norcantharin, deguelin (PI3K/Akt inhibitor), plumbagin (quinonoid substrate of ABCG2) and ionophore salinomycin. All these compounds significantly decreased or completely eliminated SP cells at low nontoxic doses in flow cytometry-based Hoechst 33342 staining assays. However, clonogenicity of SP cells treated by salinomycin was only slightly affected compared to control SP cells by clonogenic assay in vitro.In addition, Hedgehog pathway inhibitor cyclopamine (10 μM; decreased by 82%), as well as its analog tomatidine (10 μM; decreased by 64%), significantly decreased the percentage of SP cells, while sonic hedgehog agonist purmorphamine (0.8 μM; decreased by 17%) only modestly decreased the percentage of SP cells. To study these substantial inhibitory effects of tested compounds, the clonogenic assays were performed in vitro. Finally, the effect of drugs and compounds against SP cells was also evaluated in co-culture with bone marrow stromal cells, which confer growth and survival in MM. Importantly, the SP fraction was decreased by these agents, whereas no effect of hedgehog agonist and plumbagin was detected. Conclusions:Our studies confirmed the tumorigenic potential of SP cells isolated from established MM cell lines and identify the impact of targeted therapies against these cells, providing the rationale for further studies to evaluate the clinical potential of therapeutic targeting of SP cells in MM. Disclosures:Richardson:Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Anderson:Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Mitsiades:Millennium: Consultancy, Honoraria; Novartis Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Merck &Co.: Consultancy, Honoraria; Kosan Pharmaceuticals: Consultancy, Honoraria; Pharmion: Consultancy, Honoraria; Centrocor: Consultancy, Honoraria; PharmaMar: Patents & Royalties; OSI Pharmaceuticals: Research Funding; Amgen Pharmaceuticals: Research Funding; AVEO Pharma: Research Funding; EMD Serono: Research Funding; Sunesis: Research Funding; Gloucester Pharmaceuticals: Research Funding.

Disease recurrence in a transplant kidney in a patient with extramedullary plasmacytoma

Renal transplantation in patients with malignancy is controversial. Renal transplantation is generally not considered for patients with multiple myeloma (MM) because of their extremely poor prognosis. There are few reports of MM recurrence among kidney transplant recipients. We present a case of disease relapse of plasmacytoma in a transplanted kidney. We present a patient with extramedullary plasmacytoma, who responded well to chemotherapy and underwent allogenic renal transplantation. He relapsed after 4 years with progression to extramedullary plasmacytoma. Despite minimal clinical symptoms, the patient had developed myeloma cast nephropathy and acute renal failure. His renal failure settled after excision of tumor. Extramedullary plasmacytoma as a mode of relapse is highly unusual. Experience of renal transplantation in MM is limited. In the literature, the recurrence of MM is mentioned as a severe complication with a poor graft prognosis. Extramedullary plasmacytoma as a mode of relapse is highly unusual. It should not be considered as a contraindication for transplantation. Renal transplantation for patients with end stage renal disease (ESRD) due to MM is possible. But large prospective studies are needed to develop a strategy for preventing multiple myeloma recurrence.

A Case of Multiple Pulmonary Plasmacytomas after Complete Remission of Multiple Myeloma

Extramedullary plasmacytoma (EMP) is a rare disorder that typically occurs in the upper airway. Although the condition rarely arises in the lungs, a few cases have been reported. Here, we report a case of pulmonary plasmacytoma in 66-year-old man, who had been treated with VAD (vincrestine, adriamycin, dexamethasone) chemotherapy for multiple myeloma. The patient had been declared clear of multiple myeloma after 4 cycles of chemotherapy. Three months later, the patient had multiple masses visible on computed tomography (CT) and on positron emission tomography-computed tomography (PET-CT) with hot uptake. Subsequent studies using CT-guided needle biopsy and immunohistochemical stain showed pulmonary plasmacytoma. Bone marrow biopsy, serum, and urine M protein tests were repeated, showing no evidence of multiple myeloma. Pulmonary plasmacytomas, as extramedullary plasmacytomas, were considered an isolated manifestation of multiple myeloma recurrence. We treated the patient with concurrent chemoradiotherapy and the pulmonary plasmacytomas regressed dramatically.

Recurrent Multiple Myeloma Following Renal Transplantation: A Case Report

Renal transplantation is generally not considered for patients with multiple myeloma (MM) because of their extremely poor prognosis. However, for patients in remission, it offers an alternative to dialysis. There are few reports of MM recurrence among kidney transplant recipients. We report a 57-year-old white man with end-stage renal disease (ESRD) and known multiple myeloma in remission who underwent kidney transplantation. Eighteen months after transplantation upon routine follow-up, he was observed to have an elevated creatinine with no evidence of recurrence of myeloma upon bone marrow aspiration. Light microscopy and immunoflorescence of a renal biopsy showed chronic scarring of the kidney owing to cast nephropathy consistent with MM recurrence. Repeat bone marrow aspiration 1 week later confirmed this diagnosis. A review of the literature of prior studies suggested that it is reasonable to perform renal transplantation in patients with ESRD due to MM in remission, but large prospective studies would help to develop a strategy for prevention of multiple myeloma recurrence.

Multiple Myeloma Recurrence Presenting as Bilateral Breast Masses

Multiple Myeloma Recurrence Presenting as Bilateral Breast Masses

HEMATOLOGIC AND RENAL RECOVERY IN A PATIENT WITH LIGHT-CHAIN MULTIPLE MYELOMA AND END-STAGE RENAL DISEASE AFTER TWO CONSECUTIVE STEM CELL TRANSPLANTS.

We describe here an interesting case of multiple myeloma with end-stage renal disease who responded to two consecutive stem cell transplantations. A 69-year-old white male presented in May 2000 with generalized malaise and acute renal failure Workup revealed light-chain multiple myeloma. Bone marrow examination revealed > 90% atypical plasma cells. Blood tests showed β2-microglobulin of 35.5. Twenty-four-hour urine examination revealed kappa light chain, with total protein excretion of 2,400 mg. Patients received four cycles of VAD (vincristine, Adriamycin, and Decadron) chemotherapy with partial response, followed by autologous peripheral blood stem cell (PBSC) transplant in October 2000. Conditioning regimen was melphalan 140 mg/m2. The patient was in complete remission post-transplant. Hemodialysis was continued for persistent renal failure until March 2002. Renal function improved gradually, and the patient remained in remission and free of hemodialysis. In September 2005, he had a recurrence of his renal failure and multiple myeloma. Hemodialysis was reinstituted. Bone marrow examination revealed recurrence of multiple myeloma. Twenty-four-hour urine examination revealed kappa light chain of 4,750 mg. Patients underwent second autologous stem cell transplantation using PBSCs after conditioning with melphalan 140 mg/m2. Post-transplant patients had 80% reduction in urinary light chain. Dialysis was needed for 6 months post-transplant, after which the patient had recovery of renal function. Post-transplant patients were treated with the immunomodulating and antiangiogenic agent thalidomide and then with the proteosome inhibitor bortezomib because of intolerance to thalidomide. The patient is now in complete remission. To date, very few cases have been described of patients receiving stem cell transplant for multiple myeloma with end-stage renal disease. However, no case has been described in which patient received two stem cell transplants and who regained renal function, as in this case. Patients with multiple myeloma and end-stage renal disease should be treated vigorously with dialysis and high-dose chemotherapy followed by stem cell transplantation. Second transplantation needs to be considered for recurrence of disease and renal failure. This may improve the quality of life as well as prolong disease-free and overall survival.

Dural plasmacytoma mimicking meningioma in a patient with multiple myeloma

Apart from calvarial infiltration, intracranial involvement in multiple myeloma is uncommon. Diffuse leptomeningeal invasion with or without parenchymal involvement is most common. Dural infiltration without involvement of the parenchyma, leptomeninges or skull is rare. The differential diagnosis of a dural plasmacytoma includes meningioma, which has a similar MRI appearance, metastasis, lymphoma and sarcoma of the dura mater. We present a patient with multiple myeloma presenting with an intracerebral mass mimicking a meningioma on MRI. Multiple myeloma had been diagnosed seven years previously. The patient presented with headache and speech disturbance 12 months after autologous peripheral stem cell transplantation for recurrence of multiple myeloma. MRI revealed a left temporal extra-axial mass with a dural tail mimicking meningioma. Histopathological examination of the mass after excision showed multiple myeloma immunopositive for IgG, kappa light chain and CD38. There was no recurrence after postoperative radiotherapy. Plasmacytoma should be considered in the differential diagnosis of a solitary dural mass, particularly in a patient with multiple myeloma.

Intradural recurrence of multiple myeloma during the hematological complete remission

Intradural recurrence of multiple myeloma during the hematological complete remission