Artykuły w czasopismach: „Multiple myeloma Chemotherapy”

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Durie, Brian G. M. "Chemotherapy of multiple myeloma". Baillière's Clinical Haematology 4, nr 1 (styczeń 1991): 181–95. http://dx.doi.org/10.1016/s0950-3536(05)80290-2.

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Kogan, Michael, i Adnan H. Siddiqui. "Intracranial Multiple Myeloma After Chemotherapy". Archives of Clinical and Medical Case Reports 01, nr 02 (2017): 42–44. http://dx.doi.org/10.26502/acmcr.9655008.

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Lokhorst, H. M., O. J. A. Th Meuwissen, E. J. E. G. Bast i A. W. Dekker. "VAD chemotherapy for refractory multiple myeloma". British Journal of Haematology 71, nr 1 (styczeń 1989): 25–30. http://dx.doi.org/10.1111/j.1365-2141.1989.tb06269.x.

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Peest, D., H. J. Schmoll, I. Schedel, S. Glück, K. Schumacher i H. Deicher. "VBAMDex chemotherapy in advanced multiple myeloma*". European Journal of Haematology 40, nr 3 (24.04.2009): 245–49. http://dx.doi.org/10.1111/j.1600-0609.1988.tb00831.x.

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Terrovitis, John V., Charis Matsouka, Athanassios Anagnostopoulos, Maria I. Anastasiou-Nana i Athanassios Meletios Dimopoulos. "Hemophagocytic Lymphohistiocytosis After Chemotherapy for Multiple Myeloma". Clinical Lymphoma 5, nr 3 (grudzień 2004): 194–96. http://dx.doi.org/10.3816/clm.2004.n.026.

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Alexanian, Raymond, Bart Barlogie i Gerard Ventura. "Chemotherapy for resistant and relapsing multiple myeloma". European Journal of Haematology 43, S51 (24.04.2009): 140–44. http://dx.doi.org/10.1111/j.1600-0609.1989.tb01507.x.

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Vidarsson, Brynjar, Svanhvit Olafsdottir i Sigrun Reykdal. "VASP Chemotherapy in Patients with Multiple Myeloma." Blood 106, nr 11 (16.11.2005): 5189. http://dx.doi.org/10.1182/blood.v106.11.5189.5189.

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Abstract Introduction: Multiple myeloma (MM) is a malignant disorder of plasma cells resistant to chemotherapy. Various chemotherapy protocols are available for patients with MM, including VAD (vincristine, adriamycin, prednisolon) and MP (melphalan, prednisolon). These therapies aim to slow disease progression and/or prepare the patient for stem cell transplantation (SCT), the standard of care for MM patients younger than 70. An additional regimen, VASP, consisting of etoposide 50mg/m2 IV on day 1 and 100mg/m2 PO on days 2–4, adriamycin 25mg/m2 IV on day 1, cyclophosphamide 500mg/m2 IV on day 1 and dexamethasone 40mg PO qd on days 1–4, has been used in Iceland for the past 18 years. Due to the advantage of outpatient administration of VASP compared to VAD (96 hour hospital admission or indwelling venous access device with risk of extravasation), VASP has increasingly become the preferred chemotherapeutic regimen for Icelandic MM patients. Although our experience shows that VASP is comparable to VAD with respect to efficacy and toxicity, we are unaware of previous studies in support of this. The aim of this study was therefore to evaluate the efficacy and toxicity of VASP chemotherapy as it has been used in Iceland. Patients and methods: Medical records of all MM patients treated with VASP chemotherapy over a 15-year period (1990–2004) were retrospectively analyzed. Baseline disease characteristics were assessed, as was information about disease progression and previous therapy. Response to VASP (CR, PR and NR; EBMT criteria) and toxicity was documented. Survival was evaluated by the Kaplan-Meier method. Results: Of the 26 patients receiving VASP chemotherapy, 22 (12 male, 10 female) were included in this study (4 records incomplete or absent). Mean age was 64 years (range 35–86). 14 patients had IgG, 7 IgA, and 1 patient had no measurable paraprotein. 15 of the 22 patients had previously been treated with 1–2 courses of chemotherapy including VAD. Each patient received on average 5,3 courses of VASP (range 1–11). A response was seen in 17 patients (77.3%) (2 CR, 15 PR) and 5 (22,7%) showed no response. Three patients not responding to initial VAD therapy demonstrated a subsequent PR to VASP. Of the 22 patients, 15 died during the 15 years of study, resulting in a mean overall survival (OS) of 3,8 years (0,9–10,5) from diagnosis of MM and 2,0 years after VASP therapy (0–3,4). 33 of 116 VASP courses resulted in hospitalization (28,4%). Neutropenia was seen after 38,8% of the courses (nadir 0.5 x 109/L; 77.3% after the first course) and G-CSF was used in 56% of cases. Neutropenic fever was seen after 10.6% of courses and infection was documented in 15,5% of patients (bacteremia 13.6%). Transfusion of PRBC’s was required after 25 of the 116 courses but platelets after only three. Conclusion: We present data supporting the efficacy and safety of VASP chemotherapy for MM patients. Our total response rate of 77,3% compares favorably with other therapies such as VAD, and survival and toxicity is also comparable to other therapies. Although small, this is the first study we are aware of on VASP therapy for MM. Further studies, preferably larger and prospective, are required to confirm the efficacy and toxicity of VASP chemotherapy for MM.

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Minařík, Jiří, i Sabina Ševčíková. "Immunomodulatory Agents for Multiple Myeloma". Cancers 14, nr 23 (23.11.2022): 5759. http://dx.doi.org/10.3390/cancers14235759.

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The treatment of multiple myeloma (MM) has undergone a significant paradigm shift in the last 20 years, from conventional chemotherapy to more tumor-specific treatments, based on the interference with pathogenesis of the malignant clone as well as the bone microenvironment [...]

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Katagiri, Daisuke, Eisei Noiri i Fumihiko Hinoshita. "Multiple Myeloma and Kidney Disease". Scientific World Journal 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/487285.

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Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis.

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Bensinger, William I. "Hematopoietic Cell Transplantation for Multiple Myeloma". Cancer Control 5, nr 3 (maj 1998): 235–42. http://dx.doi.org/10.1177/107327489800500304.

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Background Multiple myeloma (MM) is a malignant plasma cell disorder with a median survival of three years. Despite the development of numerous conventional chemotherapy regimens and interferons, there has been little progress in improving the survival of patients with MM. Very high-dose chemoradiotherapy and autologous or allogeneic hematopoetic stem cell transplantation (HSCT) can result in high complete remission rates, even in patients with advanced disease. Methods A prospective, randomized study has shown that autologous HSCT results in superior response rates, progression-free survival, and disease-free survival compared with conventional chemotherapy. This is the first real advance in the treatment of this disease in 30 years. Unfortunately, few, if any, patients with MM who receive autologous HSCT are cured. Results Allogeneic HSCT can be curative for a fraction of patients with MM. However, very high transplant-related morbidity and mortality limit the application of allografts to younger patients with compatible donors. Conclusions Challenges for the future include the development of less intensive or more disease-specific chemotherapy regimens that preserve the antitumor activity but are less toxic, improvement in the control of graft-vs-host disease in the case of allografts and, for autologous graft recipients, the development of vaccines and cytotoxic lymphocytes to augment a graft vs myeloma effect.

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&NA;. "High-dose chemotherapy + stem cells for multiple myeloma". Inpharma Weekly &NA;, nr 1387 (maj 2003): 13. http://dx.doi.org/10.2165/00128413-200313870-00036.

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Rohatgi, Nidhi, Xianglin L. Du, Ann L. Coker, Lemuel A. Moye, Michael Wang i Shenying Fang. "Chemotherapy and Survival for Patients With Multiple Myeloma". American Journal of Clinical Oncology 30, nr 5 (październik 2007): 540–48. http://dx.doi.org/10.1097/coc.0b013e3180592a30.

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Anderson, H., JH Scarffe, M. Ranson, R. Young, GS Wieringa, GR Morgenstern, L. Fitzsimmons i D. Ryder. "VAD chemotherapy as remission induction for multiple myeloma". British Journal of Cancer 71, nr 2 (luty 1995): 326–30. http://dx.doi.org/10.1038/bjc.1995.65.

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Puri, Sonam, Jitesh Joshi, Olga Derman, Noah Kornblum, Amit Verma, Ira Braunschweig i Ramakrishna Battini. "Ocular Complications of Bortezomib Therapy in Multiple Myeloma". Blood 124, nr 21 (6.12.2014): 5743. http://dx.doi.org/10.1182/blood.v124.21.5743.5743.

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Abstract Introduction: Bortezomib (Velcade¨; V), a proteasome inhibitor, is currently FDA (Food and Drug Administration) approved for the treatment of multiple myeloma (MM) and relapsed mantle cell lymphoma. Common side effects reported with its use include thrombocytopenia, fatigue, peripheral neuropathy and neutropenia. Ocular complications associated with bortezomib are less well described. We describe 6 patients with multiple myeloma who developed meibomitis, multiple chalazions and blepharitis after treatment with bortezomib containing regimens, resulting in delay and in some cases termination of the therapy. Methods: We reviewed the charts of forty patients who received induction chemotherapy for multiple myeloma between June 2013-June 2014 at Montefiore Medical Center, New York. Charts were reviewed for data pertaining to demographics, chemotherapy regimen and schedule as well as follow up of ocular symptoms. Results: Six of these forty (15%) patients complained about bilateral eye soreness, itching and redness. They did not have any evidence of viral or upper respiratory infections. Ophthalmology evaluation showed blepharitis, meibomitis and multiple chalazion. Majority of the patients were 60 years or greater, with 50% African-Americans. Half of the cases had stage 3 MM with a median duration of chemotherapy 8 weeks prior to onset of ocular symptoms. 4 of these 6 patients received VCD regimen (Bortezomib via subcutaneous route and Cyclophosphamide/ Dexamethasone as tablets) while the remaining 2 patients received VD and VCD-R (addition of Lenalidomide) via intravenous and subcutaneous route respectively. Ocular symptoms led to a 1-3 week delay in the next cycle of chemotherapy. These symptoms promptly responded to withdrawal of chemotherapy and other conservative measures. Chemotherapy was resumed in 4 out of 6 patients, with recurrence of chalazion in two patients within 3 weeks of starting Bortezomib. Conclusions: Ocular symptoms are commonly seen but rarely reported with bortezomib therapy. They can adversely affect patient's quality of life as well as lead to interruption in chemotherapy. Although these symptoms respond well to withdrawal of chemotherapy and conservative measures, the rate of recurrence is high once bortezomib is resumed. Awareness of these complications and early intervention can potentially avoid treatment delay. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Kristinsson, Sigurdur Yngvi. "Thrombosis in Multiple Myeloma". Hematology 2010, nr 1 (4.12.2010): 437–44. http://dx.doi.org/10.1182/asheducation-2010.1.437.

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Abstract Patients with multiple myeloma (MM) are at an increased risk of venous and arterial thrombosis. The pathogenesis remains unclear, but probably involves several factors such as activation of procoagulant factors, acquired activated protein C resistance, and inflammation. In addition to general risk factors for venous thromboembolism, such as older age, immobility, surgery, and inherited thrombophilia, there are some MM-specific and treatment-related factors that contribute to the increased risk. The risk for venous thromboembolism is high when patients are treated with thalidomide or lenalidomide in combination with dexamethasone or multi-agent chemotherapy. Thromboprophylaxis should be given in these settings. Which agent is the most appropriate is a matter of debate, but aspirin, low-molecular-weight heparin, and warfarin all seem to be effective. This review discusses risk factors for thromboembolism in MM and general, disease-specific and treatment-related mechanisms for thrombosis. Recommendations for thromboprophylaxis are described and treatment choices for venous thrombosis in MM patients are reviewed.

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Chng, Wee Joo, Lee Gong Lau, Noorainun Yusof i Benjamin M. F. Mow. "Targeted Therapy in Multiple Myeloma". Cancer Control 12, nr 2 (kwiecień 2005): 91–104. http://dx.doi.org/10.1177/107327480501200204.

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Background: Multiple myeloma (MM) is an incurable malignancy. Recent insights into its biology has allowed the use of novel therapies targeting not only the deregulated intracellular signaling in MM cells but also its interaction with the bone marrow microenvironment that confers drug resistance, growth, and survival advantage to the malignant cells. Methods: We review and summarize the recent advances in our knowledge of myeloma biology as well as the mechanism of action and clinical efficacy for novel therapeutic agents in clinical trials. Results: Several novel therapeutic agents are currently in clinical trials. Thalidomide is already established for both initial and salvage treatment. Bortezomib is being tested alone and in combination with conventional chemotherapy in various settings. Other agents are less effective in producing response but have been able to stabilize disease in patients with relapsed and/or refractory disease, such as arsenic trioxide, farnesyltransferase inhibitors, 2-methoxyestradiol, and vascular endothelial growth factor receptor inhibitors. Insights into drug resistance mechanism have also led to the development of novel agents that sensitize myeloma cells to chemotherapy (Bcl-2 antisense). Gene expression studies have in many instances identified pathways other than the intended target of the drug and have provided insights into the therapeutic mechanisms. Conclusions: In the future, patients with MM will have more therapeutic options available than ever before. The challenge will be to identify patient subgroups that will benefit most from the different therapies and then determine how these biologically based therapies could be combined and incorporated into the overall management of patients.

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Lonial, Sagar. "Relapsed Multiple Myeloma". Hematology 2010, nr 1 (4.12.2010): 303–9. http://dx.doi.org/10.1182/asheducation-2010.1.303.

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Abstract Advances in treatment options for patients with multiple myeloma have made a significant impact on the overall survival of patients and have helped achieve levels of response and duration of remission previously not achievable with standard chemotherapy-based approaches. These improvements are due, in large part, to the development of the novel agents thalidomide, bortezomib, and lenalidomide, each of which has substantial single-agent activity. In addition, a large number of second-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. To better interpret clinical trials performed in the relapsed setting, it is important that definitions of relapse categories are used to help better pinpoint the specific benefit for a given therapy, especially in the combination therapy setting as it aids in determining if ongoing work should be continued or abandoned for a given new agent. Insights from preclinical modeling and in vitro work have identified several new combinations, new targets and second- or third-generation versions of existing targets that hold great promise in the setting of relapsed myeloma. Combinations of thalidomide, bortezomib, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. Clinical trials of agents such as carfilzomib, pomalidomide, vorinostat, panobinostat, and elotuzomab are just a few of the many exciting new compounds that are being tested in phase 1 and phase 2 clinical trials for relapsed patients. Further clinical and translational testing are critical to better understanding how best to combine these new agents, as well as identifying patient populations that may best benefit from treatment with these developing new agents.

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Li, Juan, Junhe Li, Shaokai Luo i Yin Zhao. "Expression of TRAIL Receptors on the Multiple Myeloma Cells." Blood 104, nr 11 (16.11.2004): 4868. http://dx.doi.org/10.1182/blood.v104.11.4868.4868.

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Abstract Objective To study the different expression of death receptors and decoy receptors on mononuclear cells from patients with multiple myeloma and myeloma cell line KM3 and compare the different expression of TRAIL receptors after chemotherapy or exposure to doxorubicin, to explore the mechanisms by which TRAIL selectively kills tumor cells. Methods Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry was used to investigate the expression of four receptors on mononuclear cells in 23 multiple myeloma patients and myeloma cell line KM3 and 15 controls, we furthermore compared the changes of expression mode after chemotherapy and incubation of KM3 cell with sub-clinical concentration of Doxorubicin. Results There finds only DR4 and DR5 on KM3 cell line without the expression of DcR1 and DcR2. Expression of DR4 and DR5 on mononuclear cells of MM patients is higher than that of controls (P<0.05), but DcR1 and DcR2 expression was lower than that of controls (P<0.05), after chemotherapy and exposure to Doxorubicin, the expression of DR5 on MM cells was up-regulated (P<0.05) Conclusions The expression of four receptors on myeloma cells and normal controls was significantly different, which might account for the selective killing effect of TRAIL on MM cells. DR5 was up-regulated on KM3 when incubating with Doxorubicin and after chemotherapy which suggests chemotherapy agents might enhance the apopotosis of MM cells through up-regulating of DR5 receptor.

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Luca, Dragos C., i Imad Y. Almanaseer. "Simultaneous Presentation of Multiple Myeloma and Acute Monocytic Leukemia". Archives of Pathology & Laboratory Medicine 127, nr 11 (1.11.2003): 1506–8. http://dx.doi.org/10.5858/2003-127-1506-spomma.

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Abstract Acute leukemia frequently has been described as a late complication of chemotherapy with alkylating agents in patients treated for multiple myeloma. However, the simultaneous occurrence of multiple myeloma and acute leukemia in the same patient, without previous exposure to chemotherapy, is a rare association. We describe a case of concomitant involvement by multiple myeloma and acute monocytic leukemia. To our knowledge, only 9 such cases have been reported in the literature to date. We discuss the criteria used in diagnosing the 2 separate diseases and the possible mechanisms responsible for this occurrence.

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Tu, Yong-sheng, Jin He, Huan Liu, Richard Eric Davis, Robert Z. Orlowski, Joshua E. Allen i Jing Yang. "ONC201 Overcomes Chemotherapy Resistance By Upregulation of Bim in Multiple Myeloma". Blood 128, nr 22 (2.12.2016): 4476. http://dx.doi.org/10.1182/blood.v128.22.4476.4476.

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Abstract In multiple myeloma, disease relapse and drug resistance occurs in the majority of myeloma patients after standard treatment despite recent improvements offered by new therapies. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. ONC201, the founding member of a novel class of anti-tumor agents called impridones, has selective preclinical efficacy against a variety of tumor types. It is currently in phase I and phase II clinical trials for patients with advanced solid tumors and hematological malignancies. Given the pronounced sensitivity of B-cell lymphomas to ONC201, we assessed the efficacy of ONC201 in preclinical models of multiple myeloma. We treated human myeloma cell lines and primary myeloma cells isolated from bone marrow aspirates of myeloma patients with ONC201 for 72 hours. CellTiter-Glo Luminescent and annexin-V binding assays for assessing myeloma cell viability and apoptosis were performed, along with immunoblotting for cleavage of caspases, phosphorylation of signaling kinases, and expression of pro- or anti-apoptotic proteins. ONC201 treatment decreased myeloma cell viability, with IC50 values that were 1 μM to 1.5 μM, even in high risk myeloma cell line RPMI8226. The status of TP53 did not appear to affect the efficacy of ONC201, as MM.1S or NCI-H929 cells with wild-type TP53 and OPM-2 or RPMI8226 with mutated TP53 had a similar sensitivity towards ONC201. These results agree with prior reports in other tumor types that have demonstrated that the efficacy of ONC201 is independent of TP53. Western blot analysis showed increased apoptosis, cleavage of caspase-9, caspase-3, and PARP. We also found that ONC201 induced expression of the pro-apoptotic protein Bim in myeloma cells, which can occur downstream of ERK inactivation. Knockdown of Bim expression in myeloma cells by shRNAs abrogated ONC201-induced apoptosis. Phosphorylation of Bim at Ser69 by Erk1/2 has been shown to promote proteasomal degradation of Bim. In accordance with this mechanism, we observed that ONC201 treatment reduced levels of phosphorylated Erk1/2, an indicator of Erk1/2 kinase activity, and Bim pSer69. In addition, ONC201 induced apoptosis in dexamethasome-, bortezomib-, and carfilzomib-resistant myeloma cell lines with the same efficacy as in wild-type cells. As a rational strategy to increase the efficacy of ONC201 by enhancing its inhibition of proteasome-mediated Bim degradation, we tested combinations of ONC201 with proteasome inhibitors bortezomib or carfilzomib. These combinations were synergistic in reducing cell viability and enhancing Bim expression and PARP cleavage in myeloma cells. Overall, these findings demonstrate that ONC201 inhibits the Erk1/2 signaling pathway and induces Bim expression to induce apoptosis in multiple myeloma regardless of resistance to standard-of-care therapies. Our studies suggest that ONC201 should be evaluated clinically in relapsed/refractory multiple myeloma. Disclosures Allen: Oncoceutics: Employment, Equity Ownership.

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Mohamed, Muhajir, i Karen Dun. "Complex hypodiploid acute myeloid leukaemia secondary to chemotherapy for hyperdiploid multiple myeloma". International Journal of Hematology 100, nr 1 (13.05.2014): 3–6. http://dx.doi.org/10.1007/s12185-014-1594-y.

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Huff, Carol Ann, i William Matsui. "Multiple Myeloma Cancer Stem Cells". Journal of Clinical Oncology 26, nr 17 (10.06.2008): 2895–900. http://dx.doi.org/10.1200/jco.2007.15.8428.

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Multiple myeloma is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic bone disease. The disease is highly responsive to a wide variety of anticancer treatments including conventional cytotoxic chemotherapy, corticosteroids, radiation therapy, and a growing number of agents with novel mechanisms of action. However, few if any patients are cured with these modalities and relapse remains a critical issue. A better understanding of clonogenic multiple myleoma cells is essential to ultimately improving long-term outcomes, but the nature of the cells responsible for myeloma regrowth and disease relapse is unclear. We review evidence that functional heterogeneity exists in multiple myeloma and discuss potential strategies and clinical implications of the stem-cell model of cancer in this disease.

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Todaro, Juliana, Patrícia Weinschenker Bollmann, Amit Nussbacher, Luis Fernando Aranha Camargo, Bento Fortunato Cardoso dos Santos, Daniel Alvarenga, Laercio Alberto Rosemberg, David Costa de Souza Le Bihan, Cláudio Henrique Fischer i Auro del Giglio. "Multiple myeloma complicated with pseudomonas endocartiditis". Einstein (São Paulo) 10, nr 4 (grudzień 2012): 498–501. http://dx.doi.org/10.1590/s1679-45082012000400017.

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Patients diagnosed with multiple myeloma are more susceptible to infections which are the major causes of morbidity and mortality associated to this disease. The main infectious agents involved are Gram-positive bacteria. However, after chemotherapy an increase in the incidence of Gram-negative strains is observed. These bacteria are also responsible for most cases of urinary tract infections. Here is reported a rare case in a 73-year-old man with multiple myeloma who developed endocarditis due to pseudomonas.

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Chandran, Rekha, Miklos Simon i Stephen E. Spurgeon. "Concurrent Presentation of Hodgkin Lymphoma and Multiple Myeloma". Case Reports in Hematology 2013 (2013): 1–3. http://dx.doi.org/10.1155/2013/398769.

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The simultaneous presentation of the Hodgkin lymphoma and multiple myeloma in the absence of prior chemotherapy or radiation is very rare. Here, we discuss a 72-year-old patient who initially presented with generalized pruritis. Workup led to a diagnosis of multiple myeloma which progressed and required treatment. As part of his pretreatment workup, an MRI was performed to evaluate skeletal lesions. This revealed diffuse and bulky adenopathy which was confirmed by PET. A biopsy of an axillary node was consistent with the nodular sclerosing type Hodgkin lymphoma. He was treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy × 6 resulting in complete resolution of his adenopathy and pruritis as well as improvement in his myeloma.

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Berneman, Zwi N., An-Sofie Verstraete, Alain Gadisseur, Ann Van de Velde i Wilfried A. Schroyens. "The Survival of Multiple Myeloma Patients: A Single Institution Study." Blood 104, nr 11 (16.11.2004): 5223. http://dx.doi.org/10.1182/blood.v104.11.5223.5223.

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Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p < 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

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Kaneko, Haruo, Ken Shikoshi, Shuichi Annou, Masashi Takada, Motoharu Kato, Setsuro Moro, Mikio Yamauchi i Tatsuo Shirai. "VCAP Combination Chemotherapy for Multiple Myeloma in the Aged." Nippon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics 28, nr 4 (1991): 504–8. http://dx.doi.org/10.3143/geriatrics.28.504.

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Johnstone, Megan, Delaney Vinaixa, Marcello Turi, Eugenio Morelli, Kenneth Carl Anderson i Annamaria Gulla. "Promises and Challenges of Immunogenic Chemotherapy in Multiple Myeloma". Cells 11, nr 16 (14.08.2022): 2519. http://dx.doi.org/10.3390/cells11162519.

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Immunological tolerance of myeloma cells represents a critical obstacle in achieving long-term disease-free survival for multiple myeloma (MM) patients. Over the past two decades, remarkable preclinical efforts to understand MM biology have led to the clinical approval of several targeted and immunotherapeutic agents. Among them, it is now clear that chemotherapy can also make cancer cells “visible” to the immune system and thus reactivate anti-tumor immunity. This knowledge represents an important resource in the treatment paradigm of MM, whereas immune dysfunction constitutes a clear obstacle to the cure of the disease. In this review, we highlight the importance of defining the immunological effects of chemotherapy in MM with the goal of enhancing the clinical management of patients. This area of investigation will open new avenues of research to identify novel immunogenic anti-MM agents and inform the optimal integration of chemotherapy with immunotherapy.

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Ii, Frederick Richards, Morton Coleman, M. Robert Cooper i W. Perry Ballard. "Multiple Myeloma—Complete Remission with High Dose Melphalan Chemotherapy". Cancer Investigation 3, nr 1 (styczeń 1985): 15–21. http://dx.doi.org/10.3109/07357908509040604.

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Wright, A., S. Elkins, J. Files, C. Bigelow, V. Herrin i M. Sample. "THROMBOEMBOLISM IN MULTIPLE MYELOMA PATIENTS RECEIVING THALIDOMIDE COMBINATION CHEMOTHERAPY." Journal of Investigative Medicine 55, nr 1 (styczeń 2007): S302. http://dx.doi.org/10.1097/00042871-200701010-00839.

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Ucci, G., A. Riccardi, P. Dörmer, M. Danova i R. Luoni. "Early Plasma Cell Recruitment In Multiple Myeloma Following Chemotherapy". Cell Proliferation 21, nr 6 (listopad 1988): 405–9. http://dx.doi.org/10.1111/j.1365-2184.1988.tb00800.x.

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Palva, I. P., P. Ahrenberg, A. Almquist, K. Ala-Harja, J. Apajalahti, H. Hallman, A. Hänninen i in. "Aggressive combination chemotherapy in multiple myeloma. A multicentre trial". Scandinavian Journal of Haematology 35, nr 2 (24.04.2009): 205–9. http://dx.doi.org/10.1111/j.1600-0609.1985.tb01574.x.

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Palva, I. P. "Combination chemotherapy MOCCA in resistant and relapsing multiple myeloma". European Journal of Haematology 48, nr 1 (24.04.2009): 37–40. http://dx.doi.org/10.1111/j.1600-0609.1992.tb01791.x.

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Fassas, Athanasios B. T., Trey Spencer, Raman Desikan, Maurizio Zangari, Elias Anaissie, Bart Barlogie i Guido Tricot. "Cytotoxic chemotherapy following tandem autotransplants in multiple myeloma patients". British Journal of Haematology 119, nr 1 (październik 2002): 164–68. http://dx.doi.org/10.1046/j.1365-2141.2002.03772.x.

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SWAN, GEORGE W. "Optimal Control Applications in the Chemotherapy of Multiple Myeloma". Mathematical Medicine and Biology 2, nr 3 (1985): 139–60. http://dx.doi.org/10.1093/imammb/2.3.139.

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Zhan, Fenghuang, Wen Zhou, Maurizio Zangari, Hongwei Xu i Guido J. Tricot. "ALDH1 Activity Identifies Chemotherapy-Resistant Multiple Myeloma Stem Cells". Blood 118, nr 21 (18.11.2011): 990. http://dx.doi.org/10.1182/blood.v118.21.990.990.

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Abstract Abstract 990 Background: Cancer stem cells are a chemotherapy-resistant subpopulation capable of self-renewal and of regenerating bulk tumor, thereby causing relapse and ultimately patient's death. Aldehyde dehydrogenase 1 (ALDH1) has been found to be a reliable marker for cancer stem cells in many human malignancies. The purpose of this study is to investigate the stem cell–related function and clinical significance of ALDH1 in myeloma. Materials and Methods: 9 myeloma (MM) cell lines (XG6, KMS12B, ARP1, 8226, U266, H929, JJN3, OPM2, 5T33) were assessed for ALDH1 activity using the ALDEFLUOR® assay. The positive fraction was sorted using FACSAria II. The functional role of ALDH1+ cells in MM was characterized by clonogenic capacity using soft agar assays and tumorigenicity in NOD-RAG/null gamma mice. Gene expression profiling (GEP) comparison between ALDH1+ and ALDH1- cells was performed using the Affymetrix U133Plus2 chips. We also performed GEP on 9 patients including 36 samples at baseline, after chemotherapy (pre-1st and pre-2nd, post-2nd autologous stem cell transplants (ASCT), and pre-consolidation. In addition, a total of 550 samples with GEP and clinical data, obtained from published studies, were analyzed. Results: ALDH1 expression increases in the samples post-treatment compared to those at baseline using the serial GEPs obtained pre-1st, pre-2nd, and post-2nd ASCT from 9 MM patients. All 9 MM cell lines studied contained a very small subset of cells with ALDH1 activity (ALDH1+), among which XG6, KMS12B, ARP1 (human MM cell lines), and 5TGM1 (mouse MM cell line) had the highest fraction of ALDH1+ cells (3.63%, 3.67%, 1.7%, and 1.9% respectively). The colony-forming efficiency of ALDH1+ cells was almost 2× higher (1390 clones out of 5000 seeding cells) than that of the ALDH1− cells (730 clones out of 5000 seeding cells) in ARP1; p<0.01). The tumorigenicity of FACS-sorted ARP1 ALDH1+ and ALDH1− cells was compared by injecting 10,000 cells subcutaneously into the right flank of NOD-Rag/null gamma mice (n=5). After 8 weeks, ALDH1+ cells showed a greater tumor forming capacity (4/5 or 80%) than the ALDH1− group (1/5 or 20%) and also a larger average tumor volume (6.80cm3 vs 1.94 cm3). Furthermore, we treated the two groups with the bortezomib for 48 hours and found that ALDH1+ cells showed much less sensitivity than the ALDH1− cells (P < 0.01) at different bortezomib concentrations. GEP performed on XG6, KMS12B, and ARP1 human cell lines showed that 20 genes were highly differentially expressed between ALDH1+ and ALDH1− fractions. A risk score determination showed that 17 of the 20 genes were up-regulated (UBE2C, CDC2, FAM83D, TOP2A, ASPM, DEPDC1, HJURP, CDCA3, AURKA, TTK, NCAPH, CCNB1, NEK2, KPNA2, KIF14, NDC80 and AURKB) and the remaining 3 were down-regulated (CALU,228697_at, 231597_X_at). Five of the 17 up-regulated genes are linked to drug resistance (NEK2, CDC2, CCNB1 and TOP2A) and the stemness-related Notch pathway (TTK). Kaplan-Meier analyses of event-free and overall survivals were used to determine the correlation of risk score with patient outcome. These revealed inferior outcomes among the 38 patients with a high level of ALDH1 risk score compared to the remaining 313 patients with a low level of ALDH1 risk score in the TT2 trial (p<0.0001) and also among the 31 patients with ALDH1+ compared to the remaining 150 patients with ALDH1− MM cells in the TT3 trial (p=0.0007). Conclusion: Our data suggest that MM cells contain a minor but more tumorigenic ALDH1+ stem cell-like compartment consisting of chemotherapy-resistant cells, and that ALDH positivity by GEP confers inferior survival outcomes in MM patients. Future studies to perform include investigating how ALDH1 activity is linked to the stemness-related Notch pathway and whether inhibiting ALDH1 directly or indirectly is a viable target for novel anti-MM therapy. Disclosures: No relevant conflicts of interest to declare.

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Becker, Pamela S. "Genetic Predisposition for Chemotherapy-Induced Neuropathy in Multiple Myeloma". Journal of Clinical Oncology 29, nr 7 (1.03.2011): 783–86. http://dx.doi.org/10.1200/jco.2010.33.4771.

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Song, Yan, Ning Hu, Xiaowei Song i Juhong Yang. "Hsa_Circ_0007841 Enhances Multiple Myeloma Chemotherapy Resistance Through Upregulating ABCG2". Technology in Cancer Research & Treatment 19 (1.01.2020): 153303382092837. http://dx.doi.org/10.1177/1533033820928371.

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The current researches have reported that circular RNA is an important regulatory factor in the progression of various human disease. However, the function and mechanism of most circular RNAs remain unknown in cancers including multiple myeloma. Our study has confirmed that hsa_circ_0007841 is up regulated in U266 doxorubicin resistant cells (U266R) and 8226 doxorubicin resistant cells (8226R) compared to U266 parent cells (U266P) and 8226 parent cells (8226P). Silence of hsa_circ_0007841 in U266R and 8226R could reduce the half-maximal inhibitory concentration which indicated reduction in chemoresistance. In doxorubicin resistant cells, the messenger RNA and protein level of ATP-binding cassette transporters G2 increased. Silence of hsa_circ_0007841 in drug resistant cells could decrease both the messenger RNA and protein levels of ATP-binding cassette transporters G2; reexpression of hsa_circ_0007841 could block the reduction. However, overexpression of hsa_circ_0007841 could effectively upregulate the ATP-binding cassette transporters G2 messenger RNA and protein level. Inhibition of ATP-binding cassette transporters G2 could block hsa_circ_0007841 overexpression induced chemoresistance in U266P and 8226P cells. What’s more, inhibition of ATP-binding cassette transporters G2 could reduce differences of half-maximal inhibitory concentration between parent cell lines and drug-resistant cell lines. Our data collectively suggest a new model in which hsa_circ_0007841 promotes acquired chemotherapy resistance by upregulating ATP-binding cassette transporters G2 providing a novel molecular basis of chemotherapy in multiple myeloma cancer.

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Kryukov, E. V., V. N. Troyan, O. A. Rukavitsyn, S. V. Kozyrev, I. G. Daragan-Sushchov, V. P. Pop, S. A. Alekseev i E. R. Sapelnikova. "Densitometry as a monitoring method in the treatment of patients with multiple myeloma". Medical Visualization, nr 5 (28.10.2018): 106–13. http://dx.doi.org/10.24835/1607-0763-2018-5-106-113.

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The article is devoted to the study of the problem of the analysis of the degree of osteoporosis based on the results of dual-energy x-ray absorptiometry in multiple myeloma during treatment. The change in bone mineral density in patients with multiple myeloma treated with standard chemotherapy and high-dose chemotherapy with autotransplantation of hematopoietic stem cells is considered. The X-ray densitometry method can serve as an objective criterion for evaluating the effectiveness of the treatment in patients with multiple myeloma.

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Sinclair, David, Adel Resouly i Anne Spedding. "Stridor: unusual presentation of multiple myeloma". Journal of Laryngology & Otology 117, nr 10 (październik 2003): 829–31. http://dx.doi.org/10.1258/002221503770716313.

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We present a patient with multiple myeloma whose only presenting symptom was stridor caused by a subglottic stenosis. Biopsy suggested the presence of amyloid which prompted immunological investigations that showed hypogammaglobulinaemia and the presence of Bence Jones proteinuria at 0.93 g/24 hours. Further investigation demonstrated a 15 per cent plasma cell infiltrate into the bone marrow and a lytic lesion in the mid-shaft of the right femur. Chemotherapy and localized radiotherapy were commenced. This is a most unusual presentation of multiple myeloma and shows that immunoglobulin profiles should be properly investigated in such cases.

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Israelyan, E. R., C. S. Golovataya, O. K. Bondarenko, A. V. Nayda i A. K. Pudeeva. "Onset of multiple myeloma with rheumatic polymyalgia". Medical Herald of the South of Russia 10, nr 4 (26.12.2019): 98–104. http://dx.doi.org/10.21886/2219-8075-2019-10-4-98-104.

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A clinical observation of a patient presented with a typical clinic of rheumatic polymyalgia (RPM), which was a manifestation of myeloma. The relationship between rheumatic polymyalgia and giant cell arteritis (GCA) is well known, but association of RPM with lymphoproliferative diseases is rarely reported. In this case there was a clinical improvement in the patient’s condition aft er chemotherapy treatment.

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Palva, I. P., K. Ala-Harja, A. Almqvist, E. Elonen, H. Hallman, A. Hänninen, M. Ilvonen i in. "Corticosteroid is not beneficial in multiple-drug combination chemotherapy for multiple myeloma". European Journal of Haematology 51, nr 2 (24.04.2009): 98–101. http://dx.doi.org/10.1111/j.1600-0609.1993.tb01600.x.

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Salmon, S. E., J. J. Crowley, T. M. Grogan, P. Finley, R. P. Pugh i B. Barlogie. "Combination chemotherapy, glucocorticoids, and interferon alfa in the treatment of multiple myeloma: a Southwest Oncology Group study." Journal of Clinical Oncology 12, nr 11 (listopad 1994): 2405–14. http://dx.doi.org/10.1200/jco.1994.12.11.2405.

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PURPOSE Standard therapy for multiple myeloma consists of cytotoxic chemotherapy plus glucocorticoids. Interferon (IFN) alfa maintenance is reported to prolong chemotherapy-induced remissions and survival. This study evaluates induction chemotherapy, glucocorticoids, and interferon maintenance in myeloma. PATIENTS AND METHODS Five hundred twenty-two previously untreated myeloma patients were randomized to three chemotherapy regimens with differing glucocorticoid intensities. Patients who achieved remission were randomized to receive IFN or observation until relapse. Patients who failed to respond to chemotherapy received IFN alfa plus dexamethasone (DEX). RESULTS Five hundred nine patients were eligible for induction chemotherapy. Chemotherapy with higher dose-intensity glucocorticoids yielded higher response rates and improved survival (P = .02 for the three-group comparison; P < .05 for each higher glucocorticoid arm v vincristine, melphalan, cyclophosphamide, and prednisone alternating with vincristine, carmustine [BCNU], doxorubicin, and prednisone [VMCP/VBAP]). One hundred ninety-three patients who achieved remission were randomized to receive IFN alfa 3 MU three times weekly or observation. IFN was not superior to observation for relapse-free (P = .95) or overall survival (P = .39) from start of maintenance. Eighty-eight induction failures received 5 MU of IFN three times weekly plus DEX. Patients who received IFN/DEX had a median survival duration of 48 months from start of IFN/DEX. CONCLUSION Higher-dose glucocorticoids increases frequency of response to chemotherapy and prolong survival in myeloma. IFN maintenance with the dose schedule used in this trial did not prolong relapse-free or overall survival. We cannot exclude a small effect of IFN, as most individual trials do not have sufficient statistical power. Meta-analysis of randomized trials evaluating IFN maintenance in myeloma might be of value. While IFN appeared ineffective, addition of higher-dose glucocorticoids improved outcome in myeloma.

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Coss, Alan, Chen Zhou, Michael F. Byrne i Alan A. Weiss. "Relapse of Multiple Myeloma Presenting with Biliary Obstruction". Canadian Journal of Gastroenterology 24, nr 4 (2010): 237–38. http://dx.doi.org/10.1155/2010/593859.

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Pancreatic infiltration is a rare feature of multiple myeloma. A case of a 74-year-old man presenting with symptomatic biliary obstruction two years after the original diagnosis of myeloma is described. Confirmation of pancreatic infiltration with myeloma cells was performed by endoscopic ultrasound-guided fine-needle aspiration. Biliary stenting was performed at endoscopic retrograde cholangiopancreatography. Resolution of the pancreatic mass and the associated biliary stricture was observed after radiation and chemotherapy.

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Sawicki, C. P., S. A. Climans, C. C. Hsia i J. A. Fraser. "Progressive multifocal leukoencephalopathy during ixazomib-based chemotherapy". Current Oncology 25, nr 1 (28.02.2018): 99. http://dx.doi.org/10.3747/co.25.3674.

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Progressive multifocal leukoencephalopathy (pml) is a rare demyelinating disease of the central nervous system that most often affects immunocompromised individuals. It is caused by the reactivation of the John Cunningham virus (jcv), which is found in latent form in the majority of adults. We describe a 59-year-old man with multiple myeloma who developed severe neurological deficits during treatment with ixazomib-based chemotherapy. A diagnosis of pml was established with gadolinium-enhanced magnetic resonance imaging (mri) and by detection of jcv in the cerebrospinal fluid. Despite cessation of chemotherapy and treatment with mirtazapine, he had an inexorable neurological decline and died two months after presenting to hospital. Multiple myeloma and its treatments can predispose patients to opportunistic infections including pml. Although there have been case reports of pml in patients with multiple myeloma treated with bortezomib (a different proteosome inhibitor), this is, to our knowledge, the first documented case of pml in a patient treated with a regimen that includes ixazomib.

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Haegelen, Claire, Laurent Riffaud, Marc Bernard, Beatrice Carsin-Nicol i Xavier Morandi. "Dural plasmacytoma revealing multiple myeloma". Journal of Neurosurgery 104, nr 4 (kwiecień 2006): 608–10. http://dx.doi.org/10.3171/jns.2006.104.4.608.

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✓The authors describe the case of a 72-year-old woman with dural plasmacytoma revealing an immunoglobulin (Ig) G-kappa multiple myeloma (MM). She presented with headaches and left hemiparesis. Magnetic resonance imaging demonstrated a right frontal extraaxial lesion arising from the dura mater, and biological studies revealed hypercalcemia, hyperproteinemia, and a serum gamma globulin peak. A diagnosis of IgG-kappa MM was based on microscopic examination and immunohistochemical analysis of the dural plasmacytoma as well as on signs of systemic myeloma after surgery. The patient died 3 years after the first symptoms of MM despite systemic chemotherapy and no recurrence of the dural plasmacytoma. Myelomatous involvement of the dura mater is a rare occurrence given that only three cases have been reported to date. Nevertheless, this pathological entity should be differentiated from solitary dural plasmacytoma (SDP) because the prognosis is radically different. Progression seems to be correlated with systemic disease in contrast to the long-term survival associated with SDP. Careful systemic evaluation should be made in such a presentation to rule out MM, which would require different management and has a different prognosis.

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Sampat, Parth J., Maneesh Bisen, Nimisha Srivastava, Suman Rao i Teresa Gentile. "Accidental Ixazomib Overdose in a Patient With Multiple Myeloma". Journal of Investigative Medicine High Impact Case Reports 9 (styczeń 2021): 232470962110132. http://dx.doi.org/10.1177/23247096211013230.

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Multiple myeloma is the second most common hematological malignancy. Ixazomib is the first oral proteasome inhibitor approved in the United States for the management of multiple myeloma who have received at least one prior treatment. The availability of oral chemotherapeutic agents for the management of multiple myeloma has made it easier for patients who do not have to come to the hospital for chemotherapy infusions. However, many barriers are associated with oral chemotherapy, and one of them is a misinterpretation of instruction which can have deleterious effects. In this case report, we present a case of a 69-year-old male with multiple myeloma who accidentally took ixazomib daily for 3 days instead of the weekly regimen and thus coming into the hospital with an overdose. In this report, we focus on the adverse effects associated with ixazomib toxicity and how to manage the adverse reactions. Although there is no antidote available for ixazomib, supportive care is very essential in these patients.

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Rathnakumar, Geeta, Kinjalka Ghosh, Nikhil Choudhary, Narendra Kamble i Nitin Inamdar. "Study of prognostic factors in multiple myeloma". International Journal of Advances in Medicine 8, nr 11 (26.10.2021): 1694. http://dx.doi.org/10.18203/2349-3933.ijam20214131.

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Background: Multiple myeloma (MM) is cancer of the plasma cell characterized by interpatient heterogeneity, in most of the cases it is incurable. It is the second most common hematological malignancy. Overall survival of patients has significantly increased recently. Lot of research is going on for prognostic factors, which can predict disease and response to therapy. During the past decades, biomarkers: M protein and β2 microglobulin have shaped the knowledge about MM. This study was undertaken to evaluate the role of prognostic factors in newly diagnosed and few follow up patients of MM before, during and after the treatment in Indian population.Methods: We analyzed 177 samples (90 MM patients and 87 healthy control) for creatinine, calcium, phosphorus, LDH, total protein, albumin, globulin, β2M, Immunoglobulines (Igs), IgG, IgA, IgM, Kappa light chain and Lambda light chains, serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE).Results: The result of our study are significant at p<0.0001 for creatinine, β2M, LDH, albumin, globulin and immunoglobulins whereas for calcium and phosphorus results are not significant at p<0.005. We observed that the levels of β2m, creatinine, LDH and M band concentration declined during the treatment (chemotherapy).Conclusions: We conclude that these results will help the clinicians to tailor-made the chemotherapy doses for betterment of patients and improve survival rate in MM patients.

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Quesada, JR, R. Alexanian, M. Hawkins, B. Barlogie, E. Borden, L. Itri i JU Gutterman. "Treatment of multiple myeloma with recombinant alpha-interferon". Blood 67, nr 2 (1.02.1986): 275–78. http://dx.doi.org/10.1182/blood.v67.2.275.275.

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Abstract Thirty-two patients with multiple myeloma were treated with recombinant alpha-interferon clone A (rIFN alpha A) daily by intramuscular injection with an initial dose of 12 X 10(6) U/m2. Of 27 patients evaluable for response, tumor responses were obtained in seven of 14 previously untreated patients (50%) and two of 13 who had relapsed or failed prior chemotherapy (15%). In all patients who had tumor response, there was restoration from subnormal levels of serum immunoglobulins, an effect infrequently observed with chemotherapy. The median duration of tumor responses exceeded 14 months (range, 6 to 20). Moderate-to-severe fatigue was the predominant side effect and necessitated dose reductions in all patients. We conclude that treatment of early stages of multiple myeloma with rIFN alpha A is beneficial because of the substantial response rate and the improvement in the synthesis of serum immunoglobulins. rIFN alpha A has a potential role in combination with other agents in the treatment of multiple myeloma.

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Quesada, JR, R. Alexanian, M. Hawkins, B. Barlogie, E. Borden, L. Itri i JU Gutterman. "Treatment of multiple myeloma with recombinant alpha-interferon". Blood 67, nr 2 (1.02.1986): 275–78. http://dx.doi.org/10.1182/blood.v67.2.275.bloodjournal672275.

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Thirty-two patients with multiple myeloma were treated with recombinant alpha-interferon clone A (rIFN alpha A) daily by intramuscular injection with an initial dose of 12 X 10(6) U/m2. Of 27 patients evaluable for response, tumor responses were obtained in seven of 14 previously untreated patients (50%) and two of 13 who had relapsed or failed prior chemotherapy (15%). In all patients who had tumor response, there was restoration from subnormal levels of serum immunoglobulins, an effect infrequently observed with chemotherapy. The median duration of tumor responses exceeded 14 months (range, 6 to 20). Moderate-to-severe fatigue was the predominant side effect and necessitated dose reductions in all patients. We conclude that treatment of early stages of multiple myeloma with rIFN alpha A is beneficial because of the substantial response rate and the improvement in the synthesis of serum immunoglobulins. rIFN alpha A has a potential role in combination with other agents in the treatment of multiple myeloma.

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Ostrovskyi, V. L., I. M. Skrypnyk, G. S. Maslova, O. A. Shaposhnyk i L. I. Yakymyshyna. "PECULIARITIES OF MYOCARDIAL BIOELECTRIC ACTIVITY IN PATIENTS WITH PROGRESSIVE MYLTIPLE MYELOMA RECEIVING BORTEZOMIB-CONTAINING CHEMOTHERAPY SCHEMES". Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії 22, nr 3-4 (29.11.2022): 80–84. http://dx.doi.org/10.31718/2077-1096.22.3.4.80.

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Introduction. New approaches to the oncohematology management that also include multiple myeloma treatment, makes higher level of hematological remission and improve survival rates. But novel cytostatic drugs have higher incidence of cardiotoxicity. According to the modern multiple myeloma management guidelines, patients, who have no indications for bone morrow transplantation, should be treated by VRd chemotherapy scheme as a first line therapy. The VRd scheme includes: bortezomib, lenalidomid and dexamethasone. Both early cytostatic-induced cardiovascular toxicity risk factor indication and cardiovascular toxicity detection have high prognostic value due to influence on individual management strategy that include chemotherapy and supportive care. This, in turn, decreases level of late and remote cytostatic-induced myocardial injury. The aim of this study is to investigate changes of myocardial bioelectric activity in patients with progression of multiple myeloma during bortezomib-containing chemotherapy scheme. Materials and methods. 20 patients who had multiple myeloma and no concomitant cardiovascular disease were examined. All patients obtain bortezomib-containing chemotherapy scheme. The patients underwent the examination three times: before the chemotherapy, in 84th day and in 140th day. General and biochemical blood count findings were analyzed. Some points of Holter electrocardiography monitoring and standard 12-leads ECG were evaluated, including heart rate, PQ interval, and corrected QT interval. Results: multiple myeloma progression was associated with the development of anaemia in 19 (95%) of the patients and was characterized by the 1.3-fold decrease in the haemoglobin and red blood cells level compared to healthy individuals (p<0,05). Rate of conductivity disorder was in 1.4 times higher than rate of rhythm disorder in the patients with multiple myeloma. The following findings were obtained by Holter monitoring and standard 12-leads electrocardiography: rhythm disorder was found in 5 (25%) patients, while conductivity disorder was detected in 7 (35%) patients. Sinus bradycardia and premature ventricular contractions were found in 2 (10%) patients following the 4 course of chemotherapy that is 2,5 times lower than in case of multiple myeloma progression. The incidence of conductivity disorder during the specific treatment were higher in 1.1 (RR=1.1; 95% СІ 0.51-2.55) (p>0,05) times and includes first degree atrioventricular block detected in 5 (25%) patients, left anterior fascicular block found in 3 (15%) patients and incomplete right bundle branch block found in 1 (5%) patient. Conclusion. The use of bortezomib-containing chemotherapy scheme in multiple myeloma patients with low cardiovascular risk lead to the decrease on the incidence of heart rate disorders simultaneously with increasing incidence of heart conductivity disorder.

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