Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma
Verónica González‐CalleEduardo SobejanoJulio DávilaEnrique M. OcioNoemí PuigNorma C. GutiérrezRamón García‐SánzAlfonso García de CocaJosé Mariano HernándezRoberto Sosa HernándezAbelardo BárezJosé María AlonsoCarmen AguileraFernando EscalanteGuillermo Martı́nRosa LópezPilar de la FuenteJorge LabradorCarlos AguilarMaría‐Victoria Mateos
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Keywords:
Autologous stem-cell transplantation
Regimen
Clinical endpoint
Chemotherapy regimen
Progression-free survival
BackgroundHigh-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) is the most effective treatment in transplant-eligible patients with multiple myeloma (MM). The complication rate of the...
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According to the latest classification of International Myeloma Working Group(IMWG),multiple myeloma(MM)is roughly classified into two groups,asymptomatic myeloma(smoldering myeloma)and symptomatic myeloma.The former is equal to the stage Ⅰ of Durie-Salmon(DS),and patients of this type only wait and see,and do not need any therapy.The later is equal to stage Ⅱ and Ⅲ of DS,and patients of this type need therapy immediately.Autologous stem cell transplantation(ASCT)is recommended by National Comprehensive Cancer Network(NCCN)for patients with stage Ⅱ or Ⅲ myeloma with good performance status in 2007.Different therapeutic regiwen should he selected for newly diagnosed MM patients according to whether ASCT is suitable or not.
Key words:
Multiple myeloma; Therapy; Stem cell transplantation
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- Multiple myeloma is a malignant plasma-cell proliferative disorder, the second most common haematologic cancer. Treatment with high-dose therapy (HDT) and single autologous stem cell transplantation (ASCT) is a category I recommendation of the National Comprehensive Cancer Network. Double transplantation can be proposed for patients failing to achieve small a, Cyrillic very good partial response (VGPR) after a first ASCT. Aims - The aim of this study is to analyse the effect of treatment with high-dose chemotherapy and autologous stem-cell support on survival in patients with multiple myeloma, and to compare our results with the results from other transplant centres.- during a 7-year period we have performed 20 high-dose chemotherapy courses and autologous stem-cell transplantation on 17 patients (3 tandem transplantations) with multiple myeloma. In this trial we retrospectively analysed the epidemiology characteristics of these patients. Female: 9 Male - 8. Median age: 53 years (from 43-64 years).diagnosis was made according to Salmon and Durie criteria. High-dose regimen consisted of Melphalan doses of 200mg/m2. In tandem transplantations the dose of the second high-dose regimen was 140 mg/m2. The volume of CD34+ cells was approximately 3.8 x 10exp8/Kg.bw. In 3 patients we used phlebothomy as a source of added stem cells. The period from diagnosis to transplantation was 12 months. Of 17 patients 70% are alive, 5 have died (3 renal failure, 1 fatal cerebral bleeding and 1 with multiorgan failure). The disease-free survival was 22 months in our group of patients. Overall survival was 48 months and survival after transplantation was 35 months. The probability of 7 years' overall survival exists in 50% of patients.Patients treated with high-dose chemotherapy followed by autologous stem-cell support have a better survival and quality of life compared with patients treated with standard chemotherapy.
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Until now high-dose therapy (HDT) supported by Autologous Stem Cell Transplantation (ASCT) has been considered the standard of care for frontline therapy of multiple myeloma (MM) in younger patients with normal renal function, and MM is currently the first indication of ASCT.
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Multiple myeloma is a hematologic malignancy which best responses to high dose therapies (HDT). HDT with autologous stem cell transplantation (ASCT) is demonstrated for multiple myeloma treatment, although some studies suggest allogenic stem cell transplantation as better choice for younger patients. Several studies have shown the efficacy of intensive chemotherapy in increasing progression- free survival (PFS) and overall survival (OS) rates.
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Dickkopf-1 (DKK-1) protein, a soluble inhibitor of Wnt signalling, has been implicated in the pathogenesis of myeloma bone disease through the suppression of osteoblast differentiation. In this study, serum concentrations of DKK-1 were measured in 50 myeloma patients (32 at diagnosis and 18 before and after autologous stem cell transplantation (ASCT), 18 patients with monoclonal gammopathy of undetermined significance (MGUS), and 22 healthy controls. Serum DKK-1 levels were increased in MM at diagnosis compared with MGUS (mean +/- SD: 67 +/- 54 ng/mL vs. 38 +/- 13 ng/mL; p = 0.006) and controls (31 +/- 11 ng/mL; p = 0.02), while there was no difference between MGUS patients and controls. Although patients with stage 2 and 3 myeloma had higher DKK-1 values than stage 1 patients (79 +/- 63 vs. 40 +/- 13; p = 0.005), no significant correlation between serum DKK-1 and myeloma bone disease was observed. Myeloma patients before ASCT also had increased levels of DKK-1 (63 +/- 77 ng/mL; p = 0.03) compared with controls, supporting the notion that DKK-1 may be responsible for the suppressed osteoblast activity even in patients with low tumor burden. After ASCT, there was a sustained decrease in DKK-1 levels over time, while bone formation markers elevated, suggesting that the reduction of DKK-1 levels after ASCT may correlate with the normalization of osteoblast function. These results could provide the basis for developing agents that block DKK-1, thus restoring osteoblast function and counteracting the increased osteoclastogenesis observed in myeloma.
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The use of novel agents for the treatment of multiple myeloma (MM) has enabled attainment of deeper responses and the information that progression-free survival (PFS) and overall survival (OS) corr...
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Meningeal involvement of multiple myeloma is a very rare complication. Defining meningeal myelomatosis (MeM) as the presence of plasma cells in the cerebrospinal fluid in a patient with multiple myeloma, we have found 53 previously reported cases in the literature, where the diagnosis MeM has been made while the patient was alive. Using Kaplan Meier statistics we have found the median survival, from the time of diagnosis of MeM, to be 1.5 months. We report a case with MeM and possible cerebral myeloma shortly after autologous stem cell transplantation, and compare it with earlier published cases. Am. J. Hematol. 62:228–233, 1999. © 1999 Wiley-Liss, Inc.
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Abstract Multiple myeloma represents a challenge for hematologists because it has become more frequent at a young age in recent years. This is why autologous stem cell transplantation is included in the standard treatment of myeloma patients. We present the case of a 39-year-old patient who was diagnosed with non-secretory myeloma with double autologous transplantation and underwent neurosurgery for spinal cord compression caused by a plasmocytoma at D5 level. We present the evolution and complexity of this very difficult case.
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