The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P < .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.

• MeSH
• chromozomální delece * MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• hybridizace in situ fluorescenční MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 17 * MeSH
• mnohočetný myelom diagnóza   genetika   mortalita   terapie   MeSH
• nádorové biomarkery MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

We compared the outcomes of 310 patients with newly diagnosed multiple myeloma with del(17p) detected by FISH to patients with high-risk translocations (HRT) (n = 79) and standard-risk (SR) cytogenetics (n = 541). The median progression-free survival (PFS) following initial therapy for the three groups was 21.1, 22, and 30.1 months, respectively (P = 0.437- del(17p) vs. HRT); the median overall survival (OS) was 47.3, 79.1, and 109.8 months, respectively, (P = 0.007- del(17p) vs. HRT). PFS and OS for patients with relative loss of 17p (n = 21) were comparable to other patients with del(17p). The PFS was similar between the del(17p) and HRT groups when stratified for age, ISS stage or treatment. The OS of del(17p) and HRT groups were similar in presence of advanced age, ISS III stage or if patients did not receive a proteasome-inhibitor containing induction. ISS III stage, high LDH and HRT, but not the percentage of cells with del(17p) predicted shorter OS in patients with del(17p). The median OS for low (ISS I, normal LDH and no HRT), intermediate (neither low nor high-risk) and high-risk (ISS III and either elevated LDH or coexistent HRT) groups among del(17p) patients were 96.2, 45.4, and 22.8 months, respectively, allowing further risk stratification.

• MeSH
• chromozomální aberace MeSH
• chromozomální delece * MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• hybridizace in situ fluorescenční MeSH
• indukční chemoterapie MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 17 * MeSH
• mnohočetný myelom diagnóza   genetika   mortalita   terapie   MeSH
• nádorové biomarkery MeSH
• plazmatické buňky metabolismus   patologie   MeSH
• prognóza MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41-88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m2 of cyclophosphamide weekly. The best confirmed response in all 48 patients included ≥ partial response in 77%, including ≥ VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.

• MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dexamethason aplikace a dávkování   MeSH
• dospělí MeSH
• glycin aplikace a dávkování   analogy a deriváty   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   farmakoterapie   mortalita   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sloučeniny boru aplikace a dávkování   MeSH
• staging nádorů MeSH
• transplantace hematopoetických kmenových buněk MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

INTRODUCTION: Limited data exist with respect to the outcome and optimal treatment of patients with myelomatous involvement of the central nervous system (CNS). MATERIALS AND METHODS: Of 4060 patients with multiple myeloma (MM), evaluated at Mayo Clinic from 1998 to 2014, 29 (0.7%) had identifiable CNS involvement, established by the presence of atypical plasma cells in the cerebrospinal fluid (CSF) and/or identification of intraparenchymal or meningeal involvement on magnetic resonance imaging (MRI). A cohort of 87 MM patients without CNS disease served as the control group (1:3), matched by diagnosis date and gender. RESULTS: Plasma cells were detected in the CSF in 87% and MRI findings consistent with CNS involvement were noted in 82% of the patients. A bone marrow plasma cell labeling index of ≥ 3%, the presence of disease at other extramedullary sites, or peripheral blood plasma cells of > 800 per 150,000 events were associated with an odds ratio of 7.1, 10.3, and 14, respectively, for the risk of CNS involvement. Overall survival (OS) from the diagnosis of MM was significantly shorter in the CNS-MM group (median 40 months; 95% confidence interval [CI], 24-56 months) than in the control group (median, 93 months; 95% CI, 67-129 months). OS was 3.4 months from the detection of CNS disease. Patients who underwent autologous stem cell transplantation after CNS involvement (n = 7) had a median OS of 19 months (95% CI, 10-67 months) from the detection of CNS involvement. CONCLUSION: Myelomatous involvement of the CNS is a rare complication that portends a poor survival. Current therapeutic approaches appear to be largely ineffective for this subset of patients with MM.

• MeSH
• analýza přežití MeSH
• biologické markery MeSH
• dospělí MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mnohočetný myelom diagnóza   epidemiologie   patologie   terapie   MeSH
• mozek patologie   MeSH
• nádory centrálního nervového systému diagnóza   epidemiologie   sekundární   terapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• surveillance populace MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• amyloidóza komplikace   terapie   MeSH
• lidé MeSH
• mnohočetný myelom diagnóza   terapie   MeSH
• prognóza MeSH
• transplantace kmenových buněk metody   využití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• klinické zkoušky, fáze III MeSH

• MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• imunoglobuliny terapeutické užití   MeSH
• kožní nemoci diagnóza   epidemiologie   etiologie   MeSH
• lidé MeSH
• retinoidy terapeutické užití   MeSH
• thalidomid terapeutické užití   MeSH
• transplantace hematopoetických kmenových buněk využití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH