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

BACKGROUND/AIMS: Bortezomib-based chemotherapy has proven to be an effective salvage regimen for refractory/relapsed multiple myeloma patients in many clinical trials. However, few reports have shown the outcomes and adverse events of bortezomib-based salvage chemotherapy in clinical practice. METHODS: From April 2006 to September 2011, 37 patients were retrospectively analyzed. A total of 19 patients received bortezomib therapy and 18 patients received bortezomib plus dexamethasone therapy. RESULTS: The median follow-up duration was 18.13 months (range, 0.97-87.20 months). The median number of cycles administered was four (range, 1-13). The overall response rate by International Myeloma Working Group (IMWG) 2006 criteria was 64.9%, including six complete responses (16.2%). The median number of cycles to best response was three (95% confidence interval [CI], 1.36-4.64). Six patients achieved their best responses after four cycles of bortezomib therapy. The median time to progression and overall survival were 5.10 (95% CI 4.03-6.17), and 23.10 (95% CI, 9.24-36.96) months, respectively. The incidence of grade 3/4 neutropenia and thrombocytopenia was 29.7% and 64.9%, respectively. A total of 27.0% patients experienced grade 3 peripheral neuropathy. Herpes zoster developed in 11 patients (29.7%). Treatment was stopped in 22 patients (59.5%) due to adverse events after bortezomib-based therapy, and treatment-related mortality occurred in 4 of 25 deaths in total. CONCLUSIONS: Bortezomib-based therapy is a very effective salvage regimen in real clinical practice, although patients relapse after multiple chemotherapies. Despite intolerable in some patients, management of toxicities and extended cycles of therapy could benefit more patients, resulting in higher response rates.
Dexamethasone ; Drug Therapy* ; Follow-Up Studies ; Herpes Zoster ; Humans ; Incidence ; Mortality ; Multiple Myeloma* ; Neutropenia ; Peripheral Nervous System Diseases ; Recurrence ; Retrospective Studies ; Salvage Therapy ; Thrombocytopenia

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

Novel agents to treat multiple myeloma (MM) have increased complete respone (CR) rates compared with conventional chemotherapy, and the quality of the response to treatment has been correlated with survival. The purpose of our study was to show how of early response to bortezomib combined chemotherapy influences survival in patients with newly diagnosed MM who are ineligible for stem cell transplantation. We assessed patient responses to at least four cycles of bortezomib using the International Myeloma Working Group response criteria. The endpoints were comparisons of progression free survival (PFS) and overall survival (OS) between early good response group (A group) and poor response group (B group). We retrospectively analyzed data from 129 patients registered by the Korean Multiple Myeloma Working Party, a nationwide registration of MM patients. The 3 yr PFS for the A and B groups was 55.6% and 18.4%, respectively (P < 0.001). The 3 yr OS for the A and B groups was 65.3% and 52.9%, respectively (P = 0.078). The early response to at least four cycle of bortezomib before next chemotherapy may help predict PFS in patients with MM who are ineligible stem cell transplantation.
Aged ; Antineoplastic Agents/*therapeutic use ; Boronic Acids/*therapeutic use ; Disease-Free Survival ; drugs Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma/*drug therapy/mortality ; Predictive Value of Tests ; Pyrazines/*therapeutic use ; Registries ; Retrospective Studies ; *Stem Cell Transplantation ; Treatment Outcome

BACKGROUNDSignificant efforts have been made to identify factors that differentiate patients treated with novel therapies, such as bortezomib in multiple myeloma (MM). The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.

METHODSThe transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction, and the prognostic value of PRAME was determined through retrospective survival analysis. PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).

RESULTSSixty-two patients (62.0%) overexpressed PRAME. PRAME overexpression showed no prognostic significance to either overall survival (n = 100) or progression-free survival (PFS, n = 96, all P > 0.05) of patients. The patients were also categorized according to regimens with or without bortezomib. PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs. 76.9%, P = 0.071). By contrast, it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs. 63.9%, P > 0.05). When the patients were categorized into PRAME (+) and PRAME (-) groups, treatment with bortezomibcontaining regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs. 53.5%, P = 0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs. 76.9%, P > 0.05).

CONCLUSIONPRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens. Bortezomib improves PFS in patients overexpressing PRAME.

Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; metabolism ; Boronic Acids ; therapeutic use ; Bortezomib ; Disease-Free Survival ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; mortality ; Pyrazines ; therapeutic use ; Real-Time Polymerase Chain Reaction ; Young Adult

BACKGROUND/AIMS: The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a first-line treatment. Because the side effects of thalidomide at a dose of > or = 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates. METHODS: Twenty-one patients were treated in 4-week cycles, receiving 4 mg/m2 melphalan and 40 mg/m2 prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism. RESULTS: The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy. CONCLUSIONS: Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.
Aged ; Angiogenesis Inhibitors/*therapeutic use ; Antineoplastic Agents, Alkylating/*therapeutic use ; Antineoplastic Agents, Hormonal/*therapeutic use ; Confidence Intervals ; Disease Progression ; Drug Therapy, Combination ; Female ; Humans ; Kaplan-Meier Estimate ; Korea ; Male ; Melphalan/*therapeutic use ; Middle Aged ; Multiple Myeloma/*drug therapy/mortality ; Prednisone/*therapeutic use ; Risk ; Thalidomide/*therapeutic use ; Time Factors ; Treatment Outcome

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: The primary purpose of this study was to investigate the prevalence and characteristics of p16 methylation and determine the prognostic implications of the clinical data, hematologic data, and p16 methylation changes in plasma cell myeloma (PCM). METHODS: We reviewed clinical characteristics and results of laboratory tests and investigated the response to combination chemotherapy and survival time. DNA methylation of the p16 gene was tested by methylation-specific PCR. Clinical significance was evaluated. RESULTS: A total of 103 patients were enrolled in this study. The median patient age was 59.0 yr at diagnosis and the male to female ratio was 1.15:1. According to the International Staging System (ISS), patients were diagnosed as stage: I (N=17, 16.5%), II (N=41, 39.8%), III (N=39, 37.9%), or not classified (N=6). Forty-five (43.7%) patients and 36 (35.0%) patients showed abnormal karyotype and complex karyotype, respectively, on the chromosome study. The p16 methylation was observed in 39 (37.9%) of 103 patients, but there was no significant association between p16 methylation status and other clinical or laboratory factors and survival outcome. Male gender, albumin, and complex karyotype were independent prognostic factors for overall survival according to multivariate analysis (P<0.05). CONCLUSIONS: The male gender, low serum albumin level, and complex karyotype were independent poor prognostic factors for PCM. p16 methylation was relatively common in PCM, but did not influence the survival outcome.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Cyclin-Dependent Kinase Inhibitor p16/*genetics ; *DNA Methylation ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma/drug therapy/*genetics/mortality ; Neoplasm Staging ; Polymerase Chain Reaction ; Prognosis ; Republic of Korea ; Serum Albumin/analysis ; Sex Factors ; Survival Rate

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