Newly Diagnosed Childhood AML Patients Treated with Bortezomib Show Superior Survival If CD74 Is Expressed: A Report of 991 Patients from the Children's Oncology Group AAML1031 Protocol
Lisa Eidenschink BrodersenChad A. HudsonTodd A. AlonzoRobert B. GerbingLaura PardoAmanda R. LeontiTimothy P. SingletonFan‐Chi HsuLoren L. LottFangyan DaiKeely GhiradelliE. Anders KolbTodd M. CooperJessica A. PollardMichael R. LokenRichard AplencSoheil Meshinchi
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We report on the use of bortezomib for the management of chronic graft versus host disease (cGVHD) among 8 multiple myeloma (MM) patients who relapsed after reduced-intensity conditioning (RIC) allogeneic transplantation. Five patients (62%) responded to bortezomib demonstrating anti-myeloma effect. Four patients had active cGVHD, including 3 patients with severe punctate keratopathy, at the time of bortezomib administration. All showed an improvement in their condition. This is the first report showing that bortezomib may be useful in the management of cGVHD and related ocular involvement.
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Mnohočetný myelom, maligní onemocnění plazmatických buněk, zůstává stále velmi obtížně léčitelným hematoonkologickým onemocněním, pro které je nutné hledat nové možnosti terapie ovlivňující jak plazmocyty samotné, tak i mikroprostředí kostní dřeně
Hematologic malignancy
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Multiple myeloma (MM) is a malignant plasma cell disease which occured predominantly in the elderly. In recent years, due to the application of small molecular proteasome inhibitor and immunomodulator, MM has become a chronic disease with good response to new treatments rather than a deadly disease that is lack of effective treatments. However, the occurrence of drug resistance makes MM less likely to be cured, which is one of the biggest challenges in MM clinical treatment. This article will review the mechanisms of acquired resistance to bortezomib in MM, including target genes modification, bypass signaling and so forth.
Key words:
Multiple myeloma; Drug resistance; Bortezomib; Proteasome inhibitor
Plasma Cell Myeloma
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Recently, the safety and effectiveness of bortezomib for patients with multiple myeloma and renal failure has been reported. In this study, we retrospectively analyzed the 8 myeloma patients with renal failure who have received bortezomib in our hospital.One patient had already required constant hemodialysis before bortezomib.Bortezomib treatment was performed for 229 days, during which time it was injected 30 times.The other 2 patients with chronic renal failure also showed no further renal impairment due to bortezomib.In the remaining 5 patients, serum creatinine levels decreased through 2 cycles(total: 8 injection)of bortezomib treatment.Two patients were complicated with herpes zoster, and 2 patients were complicated with neuropathy in grade 3.We showed the safety and efficacy of bortezomib in Japanese patients with multiple myeloma complicated with renal failure.We should positively consider the therapeutic choice of bortezomib for the refractory myeloma with renal failure.
Refractory (planetary science)
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In some patients with multiple myeloma, extramedullary masses may be present at diagnosis or may develop during treatment. Recently, multiple myeloma has been treated using newer therapeutic regimens based on thalidomide and bortezomib. Using these drugs, positive responses to treatment, not found with conventional antineoplastic agents, have been reported along with an improvement in patient outcome. In the present study, we report on three patients with extramedullary masses associated with multiple myeloma. Although all three patients were treated with bortezomib, it was ineffective against the extramedullary masses and the clinical course of the disease differed between the three patients. We propose that the effects of bortezomib on extramedullary masses may differ from case to case and may not be evident in cases of severe disease. Also, the effects of bortezomib may not be evident in the case of myeloma cells that have left the bone marrow microenvironment, similar to thalidomide. In addition, resistance to bortezomib may manifest as extramedullary masses. (160 words in the body of abstract).
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Learning Objectives After completing this course, the reader will be able to: Discuss the efficacy of bortezomib as part of primary therapy for patients with multiple myeloma.Describe the safety of bortezomib and bortezomib-based regimens in patients with previously untreated multiple myeloma.Identify new management options for patients with treatment-naïve multiple myeloma. CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
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Proteasome inhibitor bortezomib has a very powerful anti-myeloma effect on both preclinical and clinical trails.it has been widely used in the treatment of newly diagnosed,refractory and relapse multiple myeloma.Its side effects were well tolerant and manageable.
Key words:
Multiple myeloma; Protease inhibitor
Refractory (planetary science)
Myeloma protein
Protease inhibitor (pharmacology)
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Discontinuation
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Objective The aim of this study was to assess the effect of Bortezomib on serum cystatin-C(Cys-C)in multiple myeloma and whether Cys-C can monitor tumor load.Methods We measured serum Cys-C and β2-microglobulin in multiple myeloma patients and 20 healthy controls pre-and post-Bortezomib therapy.Results Multiple myeloma patients had higher Cys-C and β2-microglobulin levels compared with healthy controls(P0.05).Treatment with Bortezomib produced a significant reduction of cystatin-C and β2-microglobulin,mainly in relapsed patients(P0.05).Conclusion Treatment with Bortezomib can significantly reduce the Cys-C levels,which can be regarded as the potential indicator to monitor tumor load,and β2-microglobulin levels of multiple myeloma patients.
Beta-2 microglobulin
Cystatin
Myeloma protein
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