Non-Hodgkin's lymphoma in the elderly

With rising age the incidence of non-Hodgkin's lymphoma (NHL), together with the fact that the proportion of people older than 65 years in Western populations will double during the next 40 years, poses the challenge to adequately meet the needs of elderly patients. After a general introduction on cancer in the elderly, a review is given concerning aspects of epidemiology and prognostic factors of NHL. Therapeutic strategies, including the use of hematopoietic growth factors, for the elderly with aggressive NHL are discussed. The future role for so-called comprehensive geriatric assessment (CGA) to appropriately determine treatment possibilities is emphasized. Much scientific work has to be performed before the true value of CGA instruments can be acknowledged. Screening instruments are discussed and the role for specially trained oncology nurses in the assessment process is stipulated.     

Treatment of aggressive Non-Hodgkin's lymphoma in the elderly

A nonanthracycline-containing chemotherapeutic combination for the treatment of intermediate and high-grade non-Hodgkin's lymphoma was evaluated. Thirty-four consecutive and previously untreated patients, with a median age of 75 (range 54-86) years, with aggressive lymphoma, received daily etoposide (60 mg/m² intravenous infusion [IVI]), cytosine arabinoside (50 mg/m² subcutaneously), and methylprednisolone (60 mg/m² IVI) on each of 5 consecutive days. Individuals with limited disease (stages I and II) (n = 9) received six, 3-day cycles of the same therapy and involved field radiation (36 Gy in 20 fractions) between the third and fourth courses. Patients with disseminated lymphoma (n = 25) received 10 cycles over 8 months of the same combination, with the addition of methotrexate (200 mg/m² on days 8 and 15), followed by leucovorin rescue (10 mg/m² orally every 6 hr for 8 doses). Of the 34 patients, 44% entered complete remission (CR), and 7 died before completing the first cycle of chemotherapy. Fifty-six percent of the patients with limited disease and 40% with disseminated lymphoma (P > 0.05) achieved CR. For all patients, median survival was 14 months (range 3 days->54 months), this being 12 and 15 months, respectively. For the entire population of responding patients, median survival has not been reached at a median follow-up of 39 months, while the median CR duration is 21 months. Ten of the 15 responders are alive in unmaintained CR at a median of 41 (range 30-54) months. Myelotoxicity was the major side effect, leading to adjustments in dose and schedule in two-thirds of the patients, although treatment changes did not affect outcome. Of the 15 deaths that occurred in this trial, in 53.3% it was unrelated to lymphoma or its therapy. Four patients that had achieved CR died of cardiovascular events (n = 2) or of progressive second malignancies (n = 2). It is concluded that cytosine arabinoside in combination regimens is effective in selected patients; this is particularly relevant in the elderly. © 1995 Wiley-Liss, Inc.     

Antibiotic resistant infections due to Streptococcus pneumoniae: impact on therapeutic options and clinical outcome

PURPOSE OF REVIEW: Streptococcus pneumoniae is a major cause of morbidity and mortality in the pediatric population. The development of increasing resistance to multiple classes of antibiotics is making treatment of infections due to this organism much more difficult. The ultimate impact of high-level antibiotic resistance on therapeutic options and clinical outcomes of various pneumococcal infections is unclear and remains to be determined. Use of the conjugate pneumococcal vaccine has markedly decreased invasive pneumococcal disease in children under 5 years of age; however, its impact on decreasing antibiotic resistance is currently unknown. RECENT FINDINGS: Studies suggest that response to therapy and clinical outcome of infections due to pneumococcal isolates with intermediate resistance to the beta-lactam antibiotics is no different from that of infections due to susceptible isolates. However, evidence is accumulating that infections caused by highly resistant pneumococcal isolates are associated with higher rates of treatment failure and mortality than infections due to susceptible strains. SUMMARY: Use of a conjugate pneumococcal vaccine in conjunction with educational intervention programs that promote appropriate and judicious antibiotic use is a safe and effective means of decreasing the prevalence of pneumococcal disease in the pediatric population, decreasing the use of broad-spectrum antibiotic agents and potentially decreasing the amount of antibiotic resistance currently being seen.     

Non-Hodgkin's lymphoma in patients under twenty years of age. A clinicopathological study.

A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma.     

Treatment results of aggressive B non-Hodgkin's lymphoma in advanced age considering comorbidity

The aim of this retrospective single institution study was to investigate the long-term outcome of sequential chemotherapy (CHT) and radiotherapy (RT) in patients >/= 70 years old, considering the International Prognostic Index (IPI) for high-grade non-Hodgkin's lymphoma (NHL) and comorbidity. The study involved 106 patients aged 70 years and above, treated between 1986 and 1998, for diffuse large B-cell NHL (DLBCL); 57% had localized disease (stage I or II) and 43% had advanced disease (stage III or IV). All patients received four to six cycles of CHOP (cyclophosphamide, hydroxy-daunorubicin, oncovin, prednisone) CHT at 14-21 d intervals, followed in 69 cases by extended-field or involved-field RT. Complete response rate was 65%; overall survival probability at 5 years was 41% in all stages. Five-year survival was 62% in patients with localized and 12% in advanced disease. There were 3% treatment-related deaths. The 5-year survival rate was 70% in patients with IPI low risk, 46% with low-intermediate risk, 28% with high-intermediate risk and 0% with high risk. Patients with cardiac problems and advanced disease were more susceptible to treatment-related toxicity. Patients with hypertension showed a high rate of vinca alkaloid-associated polyneuropathy. Most patients with localized DLBCL achieved long-term remission after CHT and RT regimens despite advanced age and frequent comorbidities. Advanced disease increased the risk for treatment-related complications and efficacy of treatment seemed limited.     

Mantle cell lymphoma: established therapeutic options and future directions

During the last few years, new insights into the biology of mantle cell lymphoma have been obtained. However, with a median survival of only 3 years, mantle cell lymphoma remains the lymphoma subtype with the poorest prognosis. At initial diagnosis most patients present with advanced Ann Arbor stage III or IV and conventional chemotherapy hardly alters the continuously declining survival curve. Recently, two prospective randomized studies of the German Low Grade Lymphoma Study Group (GLSG) clearly confirmed the superiority of a combined immunochemotherapy. In a randomized study of the European mantle cell lymphoma Network, consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation improved the progression-free survival in patients younger than 65 years. However, relapses are still observed at a high frequency. Thus, new therapeutic strategies such as radioactively labeled antibodies or molecular targeting agents (e.g. Bortezomib or flavopiridol) are urgently warranted to further improve the clinical outcome of mantle cell lymphoma.     

Non-Hodgkin's lymphoma in the thyroid: case report

The authors describe the case of a 33 year-old white female, without any clinical or laboratorial evidence of thyroiditis or clinical hypothyroidism, who presented with a rapidly enlarging anterior neck mass. Diagnosis of a follicular non-Hodgkin's lymphoma was made through histopathological and immunohistochemical analysis.     

糖类抗原CA125在非霍奇金淋巴瘤中的临床诊断意义研究

目的 探讨非霍奇金淋巴瘤(NHL)患者血清CAl25表达及其临床意义.方法 对2004年9月至2006年3月中国医科大学附属第一医院42例NHL患者检测其血清CA125水平,判断CA125与性别、临床分期、B症状、浆膜腔积液、国际预后指数评分(IPI)、血清乳酸脱氢酶(LDH)、β2-微球蛋白(β2-MG)及治疗效果之间的关系.结果 CA125升高与B症状、浆膜腔积液、IPI及LDH明显相关(P<0.05),并与病情进展有一定的关系.结论 血清CA125的测定对了解NHL疾病进展、疾病监测、评价预后和治疗反应有很大意义.     

Non-Hodgkin's lymphoma of the colon and ulcerative colitis. Case report.

The association between ulcerative colitis and lymphoma is rare. The authors report the case of a 54-year old white man who presented a clinical picture and radiological and colonoscopic findings suggesting the diagnosis of idiopathic ulcerative colitis. Histopathological and immunohistochemical studies of tissue specimens obtained at autopsy led to the diagnosis of non-Hodgkin's B-cell T-cell-rich lymphoma throughout the colon. Possible relations between ulcerative colitis and gastrointestinal lymphoma are discussed.     

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Background

Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.

Methods

Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.

Results

The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.

Conclusion

Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.

     

The church and the elderly: the impact of changing age strata on congregations

This study reports the results of a survey of forty-four Lutheran Churches in the New York metropolitan area. It describes present and projected services and programs churches offer to the elderly, specifically investigating the impact of changing age strata upon congregations. A significant relationship was found between proportion of the elderly within the congregation and the pastors' interest in developing specialized ministries to the elderly. There was also a significant relationship between the proportion of the elderly within the congregation and the pastors' interest in structural modifications of the church building. However, no significant differences were found between the proportion of elderly with the congregation and the actual programs and services to the elderly. This may be an indication that churches with high proportions of the elderly had less financial and congregational resources.     

Factor VII deficiency: defining the clinical picture and optimizing therapeutic options

Summary. Factor VII (FVII) deficiency is the most frequent among rare congenital bleeding disorders, accounting for one symptomatic individual per 500 000 population, apparently without any racial/ethnic predilection. FVII deficiency prevalence in the general population is probably higher because of the presence of asymptomatic and poorly symptomatic individuals. In accordance with the role of FVII as part of the initiating complex of the extrinsic coagulation pathway, laboratory diagnosis is easy, because FVII deficiency is the only congenital bleeding disorder characterized by isolated prolonged prothrombin time. Molecular diagnosis is available, and a broad spectrum of mutations has been characterized in the FVII gene, which is located in chromosome 13. Clinical manifestations are heterogeneous, ranging from severe life‐threatening haemorrhages, such as cerebral, gastrointestinal, and joint haemorrhages, to miscellaneous minor bleeding. The main clinical features in our database (International Registry on Congenital FVII Deficiency database, n = 515) are as follows: (i) the absence of a clear‐cut and consistent correlation between bleeding symptoms and FVII clotting levels; (ii) an excess of symptomatic women compared with men; (iii) frequent surgery‐related bleeding, which is often a diagnostic tool in previously asymptomatic individuals. Several therapeutic options are possible, including plasma‐derived and recombinant products, but therapeutic schedules, optimal dosages, and administration times still have to be precisely defined, and clinical studies, including online registries such as the Seven Treatment Evaluation Registry, are actually ongoing to achieve in a better manner a safe, rational and standardized substitution treatment for this congenital disorder.     

Non-Hodgkin's lymphoma: the evolving role of purine analogues

Indolent non-Hodgkin's lymphoma is the commonest form of lymphoma in the USA and Europe, with a long natural history with multiple responses and relapses. Indolent lymphomas include follicular lymphomas (the more frequent subtype), immunocytoma, and small lymphocytic lymphomas according to the Revised European-American Lymphoma classification. The tendency has been to use simple oral medication until patients have more advanced aggressive disease but new agents such as the purine analogues have led to re-evaluation of this approach. The newer purine analogues -- fludarabine, 2-chlorodeoxyadenosine (cladribine) and deoxycoformycin (pentostatin) -- are a group of potently lymphotoxic antimetabolite molecules. Their activity in the indolent non-Hodgkin's lymphomas, in particular in the follicular subtype, may be due to their unique ability as antimetabolites to inhibit resting as well as dividing cells. Within the last decade they have moved from salvage therapy to front-line studies. Further insight into the mechanism of action of the purine analogues will to lead to further advances in this group of diseases.     

Abdominal Aortic dissections: anatomic and clinical features and therapeutic options

Isolated abdominal aortic dissections are rare events. Their anatomic and clinical features are different from those of atherosclerotic aneurysms. We report 4 cases of isolated abdominal aortic dissection that were successfully treated with surgical or endovascular intervention. The anatomic and clinical features and a review of the literature are also presented.