OBJECTIVES: Multiple myeloma (MM) is a highly heterogeneous hematologic malignancy, with disease progression driven by cytogenetic abnormalities and a complex bone marrow microenvironment. This study aims to construct a prognostic model for MM based on transcriptomic data and lipid metabolism related genes (LRGs), and to identify potential drug targets for high-risk patients to support clinical decision-making. METHODS: In this study, 2 transcriptomic datasets covering 985 newly diagnosed MM patients were retrieved from the Gene Expression Omnibus (GEO) database. Univariate Cox regression and 101 machine learning algorithms were used for gene selection. An LRG-based prognostic model was constructed using Stepwise Cox (both directions) and random survival forest (RSF) algorithms. The association between the prognostic score and clinical events was evaluated, and model performance was assessed using time-dependent receiver operating characteristic (ROC) curves and the C-index. The added predictive value of combining prognostic scores with clinical variables and staging systems was also analyzed. Differentially expressed genes between high- and low-risk groups were identified using limma and clusterProfiler and subjected to pathway enrichment analysis. Drug sensitivity analysis was conducted using the Genomics of Drug Sensitivity in Cancer (GDSC) database and oncoPredict to identify potential therapeutic targets for high-risk patients. The functional role of key LRGs in the model was validated via in vitro cell experiments. RESULTS: An LRG-based prognostic model (LRG17) was successfully developed using transcriptomic data and machine learning. The model demonstrated robust predictive performance, with area under the curve (AUC) values of 0.962, 0.912, and 0.842 for 3-, 5-, and 7-year survival, respectively. Patients were stratified into high- and low-risk groups, with high-risk patients showing significantly shorter overall survival (OS) and event-free survival (EFS) (both P<0.001) and worse clinical profiles (e.g., lower albumin, higher β2-microglobulin and lactate dehydrogenase levels). Enrichment analysis revealed that high-risk patients were significantly enriched for pathways related to chromosome segregation and mitosis, whereas low-risk patients were enriched for immune response and immune cell activation pathways. Drug screening suggested that AURKA inhibitor BMS-754807 and FGFR3 inhibitor I-BET-762 may be more effective in high-risk patients. Functional assays demonstrated that silencing of key LRG PLA2G4A significantly inhibited cell viability and induced apoptosis. CONCLUSIONS LRGs serve as promising biomarkers for prognosis prediction and risk stratification in MM. The overexpression of chromosomal instability-related and high-risk genetic event-associated genes in high-risk patients may explain their poorer outcomes. Given the observed resistance to bortezomib and lenalidomide in high-risk patients, combination therapies involving BMS-754807 or I-BET-762 may represent effective alternatives.
Humans ; Multiple Myeloma/mortality* ; Prognosis ; Lipid Metabolism/genetics* ; Transcriptome ; Machine Learning ; Male ; Female ; Gene Expression Profiling ; Algorithms

Although the exact etiology of cutaneous angiosarcoma remains unclear, MYC gene amplification has been recently discovered as a new pathogenesis. MYC is a proto-oncogene, and aberration of MYC signaling in malignancies is associated with tumor metastasis, recurrence, and mortality. Moreover, upregulation of the miRNA polycistron, miR-17-92 cluster, were confirmed in both cutaneous angiosarcoma and multiple myeloma with MYC amplification. The correlation between MYC and miRNA expression is predictable as the coincident aberrant phenotype in two diseases. Moreover, the exploiting MYC dependency may be an attractive disease-specific strategy for the diagnosis and treatment of patients who are unaware of the causes of cutaneous angiosarcoma. Herein, a rare case of cutaneous angiosarcoma of the foot, which is also the first case of cutaneous angiosarcoma accompanied by multiple myeloma, has been described.
Diagnosis ; Foot ; Genes, myc ; Hemangiosarcoma ; Humans ; MicroRNAs ; Mortality ; Multiple Myeloma ; Neoplasm Metastasis ; Phenotype ; Proto-Oncogenes ; Recurrence ; Up-Regulation

OBJECTIVE: To investigate the effect of a rehabilitation program in terms of De Morton Mobility Index (DEMMI) score, in hematologic cancer patients after chemotherapy. METHODS: Hematologic cancer patients admitted for chemotherapy were reviewed. They received a rehabilitation program during their hospital stay. DEMMI score measurement was performed, before and after rehabilitation. Demographics, diagnosis, chemotherapy information, rehabilitation program duration, mortality, body mass index (BMI), and laboratory test results were collected. For analysis, patients were classified according to diagnosis (multiple myeloma, leukemia, and others), mortality, and additional chemotherapy. RESULTS: There was statistically significant improvement in DEMMI score of 10.1 points (95% confidence interval, 5.9–14.3) after rehabilitation. It was more evident in the multiple myeloma group, and they revealed less mortality. When patients were divided according to mortality, survivors received the program earlier, and in a shorter period than in mortality cases. Although survivors revealed higher initial DEMMI score, improvement after rehabilitation did not differ significantly. CONCLUSION: In hematologic cancer patients, rehabilitation program was effective for recovery from deconditioning, revealing significant increase in DEMMI score. Multiple myeloma patients may be good candidates for rehabilitation. Rehabilitation could be sustained during chemotherapy and for high-risk patients.
Body Mass Index ; Demography ; Diagnosis ; Drug Therapy* ; Hematology ; Humans ; Inpatients* ; Length of Stay ; Leukemia ; Mortality ; Multiple Myeloma ; Rehabilitation* ; Survivors

BACKGROUNDElderly multiple myeloma (MM) patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival (OS) time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM.

METHODSWe retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects.

RESULTSAn additive scoring system (range: 0-5), based on age, Katz's Activity of Daily Living (ADL) and Lawton's Instrumental Activity of Daily Living (IADL) ≤5 and Charlson Comorbidity Index (CCI) was developed to identify three groups: fit (score = 0); intermediate-fitness (score = 1); and frail (score ≥2). The 3-year OS was 63% in fit patients, 63% in intermediate-fitness patients, and 49% in frail patients ≥3 hematologic adverse events (AEs) were documented in 45 (35.4%) fit, 34 (34%) intermediate-fitness, and 121 (30.2%) frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness (hazard ratios [HR]: 0.99, 95% confidence interval [CI]: 0.54-1.47, P = 1.000) and in frail patients (HR: 1.16, 95% CI: 0.70-1.93, P = 0.558) compared with fit ones.

CONCLUSIONSMM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in frailty with International Staging System (ISS) II/III was the worst in all patients.

Activities of Daily Living ; Aged ; China ; Cognition ; physiology ; Female ; Geriatric Assessment ; methods ; Humans ; Kaplan-Meier Estimate ; Male ; Multiple Myeloma ; mortality ; physiopathology ; psychology ; Retrospective Studies

BACKGROUNDThalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.

METHODSMedline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings "MM " and "thalidomide ". Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings.

RESULTSOverall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95% CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24-5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43-5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95-1.63], P = 0.120).

CONCLUSIONThalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.

Disease-Free Survival ; Humans ; Immunosuppressive Agents ; therapeutic use ; Melphalan ; therapeutic use ; Multiple Myeloma ; drug therapy ; mortality ; Prednisone ; therapeutic use ; Thalidomide ; therapeutic use

BACKGROUND: We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. METHODS: The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. RESULTS: MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. CONCLUSIONS: This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Calcium/blood ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 4 ; Creatine/blood ; Female ; Hemoglobins/analysis ; Humans ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis/genetics/mortality ; Multivariate Analysis ; Prognosis ; Survival Rate ; Young Adult

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bacterial Infections/*complications/microbiology ; Bortezomib/*administration & dosage ; Female ; Gram-Negative Bacteria/isolation & purification ; Gram-Positive Bacteria/isolation & purification ; Humans ; Lymphocyte Count ; Lymphopenia/*therapy ; Male ; Middle Aged ; Multiple Myeloma/complications/*drug therapy/mortality ; Multivariate Analysis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Homologous

BACKGROUND: A change in urine output has been recently recognized as a valuable biomarker of acute kidney injury that is associated with mortality in critically ill patients. We investigated the prognostic impact of oliguria for survival outcomes in multiple myeloma (MM) patients presenting with renal impairment (RI). METHODS: Retrospective data on 98 patients with MM and RI, who received initial treatment with novel therapies, were analyzed. Oliguria was defined as a urine output of <0.5 mL/kg/h. RESULTS: The baseline median eGFR was 39.7 mL/min (range, 5.1-59.8). Achievement of renal complete response (CR) was observed in 39.8% of patients. Nine patients (9.2%) presented with oliguria at initial diagnosis, and 4 initially required dialysis. Over a median follow-up period of 17.1 months (range, 1.7-100.0), the median overall survival (OS) was 38.7 months (95% CI 25.0-52.5). Multivariate analyses indicated that oliguria at diagnosis [hazard ratio (HR) 3.628, 95% CI 1.366-9.849, P=0.011], and thrombocytopenia <100x10(9)/L at diagnosis (HR 2.534, 95% CI 1.068-6.015, P=0.035), were significantly associated with overall survival. CONCLUSION: Oliguria was significantly associated with higher mortality in MM patients with RI. Therefore, close monitoring of urine output could be important for these patients.
Acute Kidney Injury ; Critical Illness ; Diagnosis ; Dialysis ; Follow-Up Studies ; Humans ; Mortality* ; Multiple Myeloma* ; Multivariate Analysis ; Oliguria* ; Renal Insufficiency ; Retrospective Studies ; Thrombocytopenia

BACKGROUND: Metastatic pathological fractures of the spine are a major problem for cancer patients; however, there is no consensus on treatment strategy. The purpose of this study was to evaluate various treatment options by analyzing their patterns for metastatic pathological fractures of the spine. METHODS: In this study, 54 patients (male:female = 36:18) who were diagnosed with metastatic pathological fractures of spine were recruited. Demographic data, origin of cancer, type of treatment, and results were obtained from electronic medical records. Treatment options were divided into radiotherapy (RT), vertebroplasty (VP) or kyphoplasty (KP), operation (OP), and other treatments. Treatment results were defined as aggravation, no response, fair response, good response, and unknown. The survival time after detection of pathologic fractures was analyzed with the Kaplan-Meier method. RESULTS: The mean age of the patients was 62.3 years. Hepatocellular carcinoma was the most common cancer of primary origin (n = 9), followed by multiple myeloma (n = 8). RT was the most common primary choice of treatment (n = 29, 53.7%), followed by OP (n = 13, 24.1%), and VP or KP (n = 10, 18.5%). Only 13 of 29 RT cases and 7 of 13 OP cases demonstrated a fair or good response. The mean survival time following detection of pathological spinal fractures was 11.1 months for 29 patients, who died during the study period. CONCLUSIONS: RT was the most common primary choice of treatment for metastatic pathological fractures of the spine. However, the response rate was suboptimal. Although OP should be considered for the relief of mechanical back pain or neurologic symptoms, care should be taken in determining the surgical indication. VP or KP could be considered for short-term control of localized pain, although the number of cases was too small to confirm the conclusion. It is difficult to determine the superiority of the treatment modalities, hence, a common guideline for the diagnosis and treatment of metastatic pathological fractures of the spine is required.
Carcinoma, Hepatocellular/mortality/pathology ; Female ; Humans ; Liver Neoplasms/mortality/pathology ; Male ; Middle Aged ; Multiple Myeloma/mortality/pathology ; Retrospective Studies ; Spinal Fractures/etiology/mortality/*radiotherapy/*surgery ; Spinal Neoplasms/*complications/secondary ; Spine ; Treatment Outcome

BACKGROUND/AIMS: The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, beta2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). METHODS: Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. RESULTS: The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 x 109/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). CONCLUSIONS: Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM.
Adult ; Aged ; Antineoplastic Agents/adverse effects/*therapeutic use ; Biomarkers, Tumor/*blood ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Hospitals, University ; Humans ; Induction Chemotherapy ; Inflammation Mediators/*blood ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multiple Myeloma/blood/diagnosis/*drug therapy/immunology/mortality ; Multivariate Analysis ; Neoadjuvant Therapy ; Odds Ratio ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Thalidomide/adverse effects/*therapeutic use ; Time Factors ; Transplantation, Autologous ; Treatment Outcome