Bone lesions in elderly multiple myeloma

We investigated the incidence of bone lesions in elderly cases of multiple myeloma (MM) and the course of those lesions, and also evaluated the relationships of skeletal symptoms with prognostic factors, and prognosis. The subjects were 146 patients, aged 65 years or more (median age 74, range 65-97 year), who were admitted to 11 institutions between January, 1988 and December, 1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88 patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type in three patients, and non-secretory type in one patient. Bone lesions in elderly MM patients were compared with those in 65 non-elderly MM patients. Skeletal symptoms were noted in 104 patients, and bone pain in 75 patients at the time of diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26 patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in 2 patients and pathologic bone fractures in 53 patients. The occurrence rate of osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion in lumbar vertebrae was higher in elderly patients (58.7%) than that in non-elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71 patients because of the bone lesions. The relationship between the prognostic factors of MM and bone lesions was evaluated. There was a significant difference in the serum Ca level between patients with and without bone pain (P < 0.0001) and between those with and without pathologic bone fracture (P < 0.01). There was a significant difference in the appearance rate of plasma cells in the bone marrow between the patients with and without bone lesions (P < 0.05), between those with and without bone pain (P < 0.01), and between those with and without pathologic fracture (P < 0.05). There was a significant difference in the serum beta 2-microglobulin level between the patients with and without bone pain, and between those with and without pathologic fracture. There were no significant differences in survival times between elderly MM patients with and without bone lesions, bone pain and pathological bone fractures, while significant differences of survival times were found between non-elderly MM patients with and without bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These data suggest that there are some differences in bone lesions between elderly and non-elderly MM patients.     

VCAP combination chemotherapy of multiple myeloma in the aged

A comparative study between patients aged over 65 (elderly group) and those under 65 (non-elderly group) was performed to determine the therapeutic efficacy of combination chemotherapy with vincristine, cyclophosphamide, Adriamycin and prednisolon (VCAP) for untreated multiple myeloma as both induction and maintenance therapy. The subjects selected were 38 patients with untreated myeloma who presented over the 7.5 years from 1982 to 1989 (June), consisting of 14 aged over 65 and 24 aged under 65. According to the classification of Durine and Salmon, 3 and 11 patients of the elderly group were stage II and III cases, respectively, while the numbers were 8 and 16 in the non-elderly group. The results defined by Imamura's criteria showed a 61.3% (9/14) partial remission rate in the elderly group and a 66.7% (17/24) rate in the non-elderly group. The 50% survival was 43 months in the elderly group and 65.5 months in the non-elderly group, with no significant difference between the groups. Thus, VCAP therapy for the induction of remission and maintenance for multiple myeloma therapy resulted in satisfactory prolongation of life in both groups, with a low incidence of the adverse reactions.     

Clinical features,outcomes and treatment-related pneumonitis in elderly patients with esophageal carcinoma

AIM: To investigate the clinical features and prognoses of elderly patients with esophageal carcinoma and to compare the effects of radiotherapy and rates of treatment-related pneumonitis (TRP) between elderly and non-elderly patients.METHODS: A total of 236 patients with esophageal carcinoma who received radiotherapy between 2002 and 2012 were enrolled. The patients were divided into two groups: an elderly group (age ≥ 65 years) and a non-elderly group (age < 65 years). The tumor position and stage, lymph node and distant metastases, and incidence and severity of TRP were compared. Multivariate analysis was applied to identify independent prognostic factors.RESULTS: The median overall survival times after radiotherapy in the elderly and non-elderly groups were 18.5 and 20.5 mo, respectively. Cox regression analysis showed that TRP grade and tumor-node-metastasis (TNM) stage were independent prognostic factors in the elderly group. High-dose radiotherapy (> 60 Gy) was associated with a high incidence of TRP. Tumor TNM staging was significantly different between the two groups in which TRP occurred. Multivariate analysis showed that TNM stage was an independent prognostic factor. Esophageal carcinoma in elderly patients was relatively less malignant compared with that in non-elderly patients.CONCLUSION: An appropriate dose should be used to decrease the incidence of TRP in radiotherapy, and intensity modulated radiation therapy should be selected if possible.     

Prognostic factors in elderly multiple myeloma patients aged 65 years or older: Comparison with nonelderly patients with multiple myeloma

Background:   Although age is a prognostic factor in multiple myeloma (MM), the prognostic factors in elderly MM patients may be different to those in nonelderly MM patients due to the patient's age. The difference in the significance of prognostic factors between elderly MM patients and the nonelderly MM patients was studied.
Methods:   Forty-two elderly MM patients aged 65 years or older were compared with 68 nonelderly MM patients, who were less than 65 years of age. The characteristics of the elderly patients included: aged 65–81 years (median, 72 years); female/male ratio of 22 : 20; 24 IgG type cases, 13 IgA type cases, one non-secretory case and four cases of Bence-Jones type; one case of stage I, 12 cases at stage II and 29 cases at stage III. The prognostic factors were evaluated by means of univariate analysis and Cox's multivariate analysis.
Results:   The median survival time was significantly shorter in the elderly MM patients (24 months) than in the nonelderly patients (50 months) ( P  < 0.01). Of the univariate prognostic factors, corrected serum Ca (cCa), hemoglobin, serum P, bone marrow plasma cell and uric acid were significant prognostic factors in the elderly MM patients, while nine factors including those listed here, were significant in nonelderly controls. Multivariate analysis showed that serum cCa was the only independent prognostic factor ( P  = 0.019) in elderly MM patients, while serum P and bone lesions were significant prognostic factors in nonelderly MM patients.
Conclusion:   Corrected serum c. (cCa) was an independent prognostic factor in elderly MM patients.     

The significance of myelodysplasia in untreated patients with multiple myeloma]

Microscopic analysis of bone marrow smears from ten untreated patients with multiple myeloma (MM) revealed that seven patients had myelodysplastic changes. Of these, five patients had anemia alone while the other two had anemia and leucopenia. The myelodysplastic changes seen in MM were less extensive than those seen in myelodysplastic syndrome (MDS). Moreover, the dysplastic changes in MM were determined to be limited to two or three lineage cells. Dysplastic changes were observed even after clinical signs of MM had improved due to therapy. We consider that the myelodysplastic changes seen in MM can be attributed to MM itself, rather than to the coexistence of MDS and MM. Such findings suggest that the pathogenesis of MM involves a common stem cell which differentiates into multiple lineage cells.     

Registration of hematological disorders by the Kyushu Hematology Organization for Treatment (K-HOT) Study Group

The Kyushu Hematology Organization for Treatment (K-HOT) Study Group was organized in 1999 to study hematological disorders diagnosed in the participating institutions in the Kyushu district. We registered all new patients with hematological disorders and from February 2000 to the end of 2003, a total of 2908 patients had been registered. They include non-Hodgkin's lymphoma in 803 patients, leukemia in 556, multiple myeloma (MM) in 276, myelodysplastic syndrome in 273, and adult T-cell leukemia/lymphoma (ATL) in 269 followed in a decreasing order by idiopathic thrombocytopenic purpura, aplastic anemia, and other benign hematological disorders and myeloproliferative disorders. The annual incidence of MM is estimated to be much higher than that previously reported. It is also confirmed that ATL is still one of the frequently encountered lymphoid malignancies in the Kyushu district.     

Therapie des multiplen Myeloms

The multiple myeloma (MM) has an incidence of 3-4/100,000 in the Caucasian population. MM has to be distinguished from smouldering MM and monoclonal gammopathy of uncertain significance (MGUS). In younger patients (<65 years) a good long-term remission is the aim of therapy, while in the elderly patients with comorbidities the aim is a good partial remission with good quality of life. In the elderly this can be achieved with a combination of melphalan and prednisone. High-dose chemotherapy, often as a tandem transplantation, is part of standard therapy of MM patients <65 years. However, allogeneic stem cell transplantation is the only curative approach. New substances approved for treatment of relapsed MM include bortezomib, thalidomide, and lenalidomide.     

Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY

OBJECTIVES: Until recently, no prospective epidemiologic survey of lymphoma and multiple myeloma (L/MM) in European cancer patients had been conducted; furthermore, data on prevalence, incidence, and treatment patterns of L/MM were limited or unavailable. Here we define anemia prevalence, incidence, and treatment patterns, and identify anemia risk factors in European L/MM patients. METHODS: Data for a subgroup of 2360 L/MM patients in the European Cancer Anaemia Survey (ECAS) were analyzed; variables included age, gender, tumor type/stage, cancer and anemia treatment, WHO performance status, and hemoglobin (Hb) levels. RESULTS: 2316 patients were evaluable (1612 L and 704 MM). Anemia rate at enrollment was 52.5%. At enrollment, Hb levels correlated significantly with WHO scores (r = -0.306, P < 0.001). Anemia prevalence during ECAS was 72.9% (MM, 85.3%; non-Hodgkin's lymphoma, 77.9%; Hodgkin's disease, 57.4%); incidence in chemotherapy patients was 55.4%. Only 47.3% of patients anemic any time during ECAS received anemia treatment; overall Hb nadir for initiating treatment was 8.9 g/dL (epoetin, 9.5 g/dL; transfusion, 8.2 g/dL). Factors found to significantly (P < 0.03) increase anemia risk were low initial Hb, female gender, persistent/resistant disease, and platinum chemotherapy. CONCLUSIONS: L/MM patients have a high prevalence and incidence of anemia; however, anemia is not optimally treated. Anemia is common in L/MM patients and, given its known adverse impact on physical functioning and quality-of-life variables including fatigue and cognitive function, anemia management should be an integral part of their care. Predictive factors identified by ECAS may help clinicians develop optimal anemia treatment strategies for L/MM patients.     

Angiogenesis in hematologic malignancies

Angiogenesis, defined as the blood vessel generation from preexisting blood vessels, was found to play an important role in the progression of solid tumors. In addition, bone marrow-derived endothelial precursor cells may contribute to tumor angiogenesis. Recently angiogenesis induction was described in several hematologic neoplasms as leukemia, lymphoma, myelodysplastic syndrome and multiple myeloma (MM). Clinical angiogenesis research also termed as angiodiagnosis has established the prognostic relevance of markers of angiogenesis e.g., microvessel density and circulating levels of angiogenic peptides. Development of antiangiogenic treatment for hematologic neoplasms has recently been sparked by the success of Thalidomide (Thal) which has antiangiogenic properties in MM. Antiangiogenic treatment strategies are now being tested in clinical trials on several types of hematologic neoplasms.     

Autologous stem cell transplantation in the elderly including pre- and post-treatment options

Multiple myeloma (MM) is a disease of the elderly with a median age at diagnosis of 67 years in a referral population. High-dose chemotherapy (HDT) and autologous stem cell transplantation has been shown to improve survival in patients with MM in randomized trials and remains the preferred option for eligible patients. However, the randomized clinical trials demonstrating an advantage for HDT included only patients younger than 65 years and evidence supporting its role for the elderly patients has been based on retrospective reviews. The introduction of thalidomide, lenalidomide and bortezomib has changed the paradigm for treatment of myeloma and improved the outcome for these patients. Several ongoing clinical trials are evaluating the role of these novel agents in this population, specifically comparing these to HDT-based approaches. Other trials are examining the role of maintenance therapy post-HDT with these novel drugs with or without steroids. The role of HDT will be further redefined in the coming years with improvements in other therapies.     

Treatment of small cell lung cancer in the elderly: the progress and limitation of chemotherapy]

In order to assess the progress and limitation of chemotherapy in the treatment of small cell lung cancer in the elderly, we analyzed 218 patients who had entered into protocol studies between 1982 and 1990. Among those, there were 101 elderly patients (age of greater than or equal to 66 years) and 117 non-elderly patients (age of less than or equal to 65 years). Response to chemotherapy with or without chest irradiation was almost comparable for the elderly and the non-elderly; complete response rate was 52% for limited disease (LD) and 33% for extensive disease (ED) in the elderly, and it was 68% for LD and 23% for ED in the non-elderly. Survival figures of the two groups were quite similar: The median survival time was 12.6 months for the elderly and 14.5 months for the non-elderly, and the 3-year survival rate was 14% for both groups. An improvement of patient survival was observed along with the chronology of the protocols, i.e., with a escalation of dose intensity. Of interest, the improvement was rather evident in the elderly than in the non-elderly. Hematologic toxicity was considerable more frequent and severe in the elderly than in the non-elderly with non-significant statistics. The incidense of fever episodes while neutropenic was significantly more frequent in the elderly. Non-hematologic toxicity was almost comparable for the two groups, with a exception that the elderly showed a trend being predisposed to renal toxicity. In conclusion, such elderly patients as eligible for entry into a protocol study can benefit from intensive treatment as equally as non-elderly patients can.     

Negligible influence of comorbidity on prognosis of patients with small cell lung cancer: a population-based study in the Netherlands

Management of small cell lung cancer (SCLC) among elderly is complex because of decreased organ functions and interactions with comorbidity. Since elderly patients are often excluded from clinical trials, little is known about the way they are treated and outcome.We evaluated the prognostic effects of rising age and comorbidity in unselected Dutch SCLC patients (Eindhoven Cancer Registry). Elderly patients received chemotherapy less often and the dose was also reduced more often. Cardiovascular diseases, hypertension or diabetes lowered the proportion receiving combined chemotherapy and radiotherapy among patients with limited disease. About 80% of the patients receiving chemotherapy suffered from a side effect, which was not related to age. After adjustment for age, gender, stage and treatment modality, comorbidity had a negligible prognostic effect. Chemotherapy (in combination with radiotherapy) seemed to improve survival, however, toxicity and quality of life in these patients should be evaluated thoroughly in future randomized studies.     

Multiple myeloma in elderly patients: presenting features and outcome

Few studies have been performed regarding multiple myeloma (MM) in elderly patients. We report a retrospective series of 130 unselected patients with MM aged 75 yr or more at diagnosis. Presenting features were identical to those reported in younger patients, except for a higher rate of infection. Heavy comorbidity was characteristic of unselected geriatric patients. Ninety-four patients received conventional chemotherapy. The response rate was 62%. Treatment toxicity was mild. Median survival was 22 months. Durie-Salmon (DS) clinical stages II and III MM were severe and often led to death, while significantly more patients with DS stage I MM died from unrelated causes (p<0.0001). Univariate analysis showed that age > or = 85 yr, performance status > or = 2, creatinine level > or = 120 micromol/l, beta 2 microglobulin level > 4 mg/l, C-reactive protein level > 6 mg/l, platelet count < 100 x 10(9)/l, presence of infection and lack of response to chemotherapy were adverse prognostic factors for survival. In Cox multivariate regression analysis, age > or = 85 yr (p<0.0001), performance status > or = 2 (p<0.0001) and creatinine level > or = 120 micromol/l (p<0.0001) were independent factors in predicting short survival. This study provides evidence that in patients with symptomatic MM age should not be considered as a major obstacle to active treatment. Prospective clinical trials are needed in this population of patients and should include an assessment of quality of life.     

Therapy-related myeloid neoplasms after treatment for plasma-cell disorders

Therapy-related myeloid neoplasms (t-MN), including therapy-related acute myeloid leukaemia and myelodysplastic syndrome, are second primary malignancies (SPM) that are of growing importance as patients with plasma cell disorders (PCD) such as multiple myeloma (MM) are living longer with more effective therapies. Both patient-specific and treatment-specific factors likely impact the risk of t-MN development after diagnosis and treatment of PCD. Alkylating chemotherapy, especially melphalan, has been strongly tied to the risk of t-MN. More recently, there has been a shift away from long-term alkylating therapies to immunomodulatory agents and high-dose therapy with autologous stem cell transplant (HD-ASCT). This shift has led to improved survival and long-term outcomes for most MM patients. However, the risks of t-MN remain despite the improved efficacy of these treatments, and patients who develop t-MN have a poor prognosis. Understanding the risk factors predisposing MM patients to t-MN can thus help to tailor individualized therapy to maximize anti-myeloma efficacy and minimize the risks of t-MN.     

The role of race, socioeconomic status, and distance traveled on the outcome of African-American patients with multiple myeloma

The incidence and mortality of multiple myeloma (MM) in African-Americans is double that in whites. We questioned whether race, socioeconomic status, and distance traveled affect overall survival. In a retrospective review of the records of 292 patients with MM. We found that the median age was 60 years and 38 patients were African-Americans. The mean distance traveled was 67.7 miles. The median overall survival was similar in African-Americans and whites. Race, distance traveled and socioeconomic status were not independent prognostic factors for overall survival. In conclusion, socioeconomic status, distance traveled and race did not affect outcomes of MM patients treated at a specialized myeloma center.     

Optimal treatment strategy for elderly patients with hepatocellular carcinoma

BACKGROUND AND AIMS: The age distribution of patients with hepatocellular carcinoma (HCC) now peaks at nearly 70 years in Japan and this is continually increasing. Whether such elderly patients with HCC aged 80 years or older should be treated, and if so, how they should be selected for treatment remains uncertain. The present study was undertaken to determine any differences in the clinical characteristics and prognostic features between patients with HCC aged 80 years or older and those younger than 80 years of age. We also aimed to identify any significant variables in the prognosis of elderly patients with HCC aged 80 years or older. METHODS: Seven hundred and four patients with HCC, diagnosed during a 12-year period from January 1989 to December 2000, were categorized into two groups as follows: (i) 36 patients aged 80 years or older at the detection of HCC were defined as the elderly group and; (ii) 668 patients younger than 80 years of age were placed in the non-elderly group. Clinical variables were analyzed and compared between the two groups, and any significant variables in the prognosis were simultaneously determined. RESULTS: Regarding sex, viral markers, concentration of serum alpha-fetoprotein, diameter and number of tumors, Child's grade, presence of portal thrombosis, histology grade of HCC and any types of treatment, no significant difference was found between the two groups. The 1-year and 3-year survival rates in the elderly group (54.1 and 28.1%, respectively) were not significantly different from those in the non-elderly group (69.9 and 43.2%, respectively; P = 0.1053). The only significant factor in the prognosis in the elderly group was the presence of portal thrombosis, although a Child's grade of B or C was almost a significant factor with a P-value of 0.063. Tumor size measuring more than 3 cm in the greatest dimension, non-solitary tumor, Child's grade of B or C, and the presence of portal thrombosis were all found to be prognostic factors in the non-elderly group using a multivariate analysis. CONCLUSIONS: An advanced stage of HCC, not advanced age, influenced the survival rate in these elderly patients. Therefore, an optimal treatment strategy should be applied for elderly patients with HCC who demonstrate less prognostic factors in the same manner as that for non-elderly patients.     

老年自身免疫性肝炎患者临床检验特点分析

目的 探讨老年自身免疫性肝炎（AIH）患者临床检验特点。方法 回顾性分析2005年1月~2015年12月期间收治的133例AIH患者的临床资料,年龄<60岁者85例,≥60岁者48例。统计分析两组患者临床资料、生化指标和免疫学指标等差异。结果 21.3%老年组和20.0%非老年组合并干燥综合征,合并自身免疫性甲状腺炎分别为8.3%和10.6%,合并类风湿性关节炎分别为10.4%和4.7%（P<0.05）;老年患者血清ALT、AST和ALP呈低水平升高,GGT明显升高,γ-球蛋白和IgG均超过最高上限;老年组和非老年组抗核抗体阳性率分别为80.5%和77.0%,AMA分别为51.7%和55.9%,SSA阳性率分别为23.3%和15.2%,ENA分别为8.3%和7.7%（P>0.05）,非老年组DsDNA阳性率为6.3%,两组均未检出SLA/LP、LC-1和LKM;老年组红细胞MCV和MCH明显高于非老年组（P<0.05）,血Cr、Urea和胱抑素C （Cys-c）也显著高于非老年组（P<0.01）;老年组β-球蛋白显著低于非老年组,差异有统计学意义（P<0.01）。结论 老年AIH患者在合并肝外自身免疫性疾病、血生化指标、自身抗体、γ-球蛋白和IgG水平等方面与非老年组类似,但老年患者红细胞MCV和MCH明显增大,提示可能合并自身免疫性胃炎,Cys-C升高提示老年AIH患者可能合并肾脏免疫性损伤,β-球蛋白增高提示易发生肝内胆汁淤积,DsDNA仅见于非老年患者,提示中青年患者易合并多器官自身免疫病。     

多发性骨髓瘤细胞遗传学变化及其蛋白酶体抑制剂的疗效观察

目的分析多发性骨髓瘤(MM)的细胞遗传学变化及其与蛋白酶体抑制剂治疗的关系。方法对2005年1月至2006年7月北京大学人民医院29例初诊的MM患者行染色体核型检查,采用骨髓细胞24h短期培养,用常规方法制备染色体,G显带进行核型分析。22例MM患者采用传统化疗即长春新碱联合阿霉素和地塞米松(VAD)方案或马法兰与泼尼松(MP)方案;7例患者应用蛋白酶体抑制剂(硼替佐米)为主的化疗方案。比较两组患者的有效率及缓解率。结果29例MM患者中异常核型检出率为37.9%,其中有复杂和高度复杂畸变的占81.8%。采用VAD或MP方案化疗的核型正常组的有效率为81.2%,核型异常组有效率为0,差异有显著性意义(P<0.05)。应用硼替佐米为主的化疗方案中核型异常组5例均有效,核型正常组2例均有效。核型异常组硼替佐米有效率与传统化疗组相比,差异有显著性意义(P<0.05)。结论染色体核型异常的患者,应首选蛋白酶体抑制剂硼替佐米等进行治疗。     

Contribution of new immunoglobulin-derived biomarkers in plasma cell dyscrasias and lymphoproliferative disorders

New assays for serum immunoglobulin (Ig) free and heavy chain quantification were developed for routine clinical practice. Serum free light chain (sFLC) assay was shown to improve detection, management and prognostication in all plasma cell dyscrasias. More precisely, sFLC measurements proved to be prognostic for the progression of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma (MM), became markers of response and survival in amyloid light-chain amyloidosis and contributed to accurate follow-up of patients with light chain and non secretory MM. In addition, sFLC and they ratio (sFLCR) were shown useful for the prognosis and monitoring of intact Ig myeloma; their evaluation was incorporated in the new uniform response criteria. sFLC or sFLCR were also observed abnormal in B-cell non-Hodgkin lymphoma/chronic lymphocytic leukemia (CLL). Moreover, increased sFLC levels, summated sFLC or abnormal sFLCR predict shorter overall survival in early-stage CLL while increased sFLC constituted an independent, adverse prognostic factor for event-free and overall survival in diffuse large B-cell lymphoma and Waldenstrom’s macroglobulinemia. Clinical applications of heavy Ig chain separately (HLC) measurements are more recent and mainly concern MM in which HLC deriving ratios correlated with parameters of disease activity and constituted an adverse survival marker.     

Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies

Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.