Association between ApoE phenotypes and telomere erosion in Alzheimer's disease.

Although several reports suggest that Alzheimer's disease (AD) is associated with shortened telomere length, the clinical relevance of this has not yet been fully elucidated. This study was conducted to clarify the correlation of telomere length with clinical characteristics and ApoE phenotypes in 74 AD patients. Telomere length was determined from genomic DNA extracted from whole blood by quantitative real-time polymerase chain reaction. We found no significant difference in telomere length between the AD and non-dementia elderly control (n = 35) groups. Furthermore, no significant correlation was found among telomere length and the severity of cognitive decline and disease duration, age, or gender difference. However, telomere length was significantly shorter in AD patients with the ApoE4 homozygote than in those with the ApoE4 heterozygote (p < .001) and noncarriers (p < .001). These findings suggest that shortened telomere length may be associated with the ApoE4 homozygote in AD patients.

Clinical results and issues of acute myeloid leukemia in elderly patients aged 75 years and older.

AIM: Clinical outcomes of acute myeloid leukemia (AML) in elderly patients still remain unsatisfactory and the optimal treatment has yet to be clearly established. This report describes the results of a retrospective study of clinical outcomes and prognostic factors of AML in patients aged 75 years and older. In addition, we aimed to elucidate the situation of patients with AML accompanied by dementia, which has been largely ignored in previous studies. METHODS: The subjects consisted of 31 patients with untreated AML (including previous myelodysplastic syndrome: AML/MDS). All patients underwent chemotherapy, with 25 undergoing conventional therapy and six undergoing low-intensity therapy. RESULTS: Complete remission was obtained in 16 of the 31 cases (51.6%), with a 3-year survival rate of 11.5%. However, in seven cases, Alzheimer's disease (AD) was observed. Although we were able to perform induction therapy in each of these cases, consolidation therapy was difficult in cases of moderate AD. CONCLUSION: The results of this study suggest that even very elderly patients can benefit from chemotherapy. However, it is thought that the treatment selection for cases which are complicated by moderate to severe dementia should be determined carefully while considering the patient's quality of life.

Vascular risk factors and progression in Alzheimer's disease.

AIM: To determine whether vascular risk factors such as hypertension, diabetes and hypercholesterolemia affect the progression of Alzheimer's disease (AD). METHODS: We followed up 150 consecutive outpatients with probable AD for 24-60 months. Severity of cognitive impairment was assessed using the Mini-Mental State Examination (MMSE). We investigated the influence of vascular risk factors and other demographic and clinical conditions (including age, sex, education, initial MMSE score and follow-up time) on annual MMSE score changes. RESULTS: Multiple regression analysis revealed that age, education and hypertension were significant variables associated with annual MMSE score changes. Younger, more educated patients with hypertension showed greater decline in annual MMSE scores. There were no significant correlations of annual MMSE score changes with other vascular factors or demographics, including sex, initial MMSE score, diabetes or hypercholesterolemia. CONCLUSION: Younger, more educated patients are more likely to have faster cognitive decline. In addition, hypertension may also be associated with a greater rate of disease progression. Our results suggest the importance of prevention and treatment for hypertension in patients with AD.

Peripheral T-cell lymphoma presenting as myelofibrosis with the expression of basic fibroblast growth factor.

Myelofibrosis is often observed in chronic myeloproliferative disorders (CMPD), but non-Hodgkin's lymphoma with diffuse myelofibrosis is rare. We describe an elderly case with peripheral T-cell lymphoma-unspecified (PTCL) presenting as diffuse myelofibrosis. Bone marrow biopsy revealed infiltration of atypical lymphocytes and diffuse myelofibrosis without any increase in megakaryocytes. To discuss the pathogenesis of fibrosis, we examined cytokines relative to fibrosis using immunostaining. The expression of basic fibroblast growth factor (bFGF) was diffusely detected in the area of extracellular matrix of bone marrow. In addition, in situ hybridization revealed that infiltrating lymphoma cells expressed bFGF mRNA. Basic FGF, originally identified based on its mitogenicity for fibroblasts, has multiple potential, influencing neoangiogenesis, bone marrow fibrosis and the proliferation of tumor cells. Basic FGF might play an important role in the pathogenesis of myelofibrosis in the present case.

[An elderly autopsy case of chronic myelomonocytic leukemia with infiltration of a giant liver cyst and multiple organs].

A 78-year-old man was referred to his local hospital at the beginning of July 2006 with low grade fever and cough, and was admitted on August 22 with pneumonia. Hematology tests on admission revealed leukocytosis, anemia, and thrombocytopenia, so he was subsequently transferred to our hospital on August 24. A diagnosis of chronic myelomonocytic leukemia (CMML) was made from the hematological findings and he was given hydroxycarbamide from September 7. Seventeen days later, abdominal CT revealed hemorrhage into a giant liver cyst, as well as both intraabdominal and intrathoracic hemorrhage. He died of hemorrhagic shock on September 25. Autopsy showed extensive infiltration of myelomonocytic leukemic cells into the walls of the liver cyst, as well as the pleura and multiple other organs. In summary, we report an elderly autopsy case of CMML with infiltration of a giant liver cyst and multiple organs.

Complex translocations derived stepwise from standard t(15;17) in a patient with variant acute promyelocytic leukemia.

We report the case of an elderly man with an acute promyelocytic leukemia variant carrying complex variant translocations. The Q-banded karyotype and spectral karyotyping method revealed a typical t(15;17), and two complex rearrangements caused by stepwise translocation derived from a typical t(15;17). Chromosomes 8 and 14 were related to these rearrangements. The patient received induction chemotherapy using all-trans retinoic acid and achieved complete remission. To our knowledge, a case with complex rearrangements, caused by apparent stepwise translocation, at diagnosis, has not been reported previously.

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma].

AIM: We examined the efficacy and adverse effects of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) or THP-COP (pirarubicin, cyclophosphamide, vincristin, prednisone) in previously untreated old-old and extremely old patients with diffuse large B cell lymphoma (DLBCL). METHODS: Subjects were 13 initial DLBCL patients consisting of 7 men and 8 women with a median age of 79 years (range 75-91 years). These patients received CHOP or THP-COP plus 375mg/m2 rituximab intravenously given on the day before each cycle. The dose was adjusted depending on the patient's age and associated complications. Administration was performed for 6 to 8 cycles, whenever possible. RESULTS: Seven patients (54%) achieved a complete response (CR), 4 (31%) achieved a partial response (PR), 2 (15%) failed to respond. The 2-year survival rates were 62%. The CR rate and survival rate were higher than in patients previously treated with CHOP alone in our hospital, but there was no statistically significant difference. The most frequent adverse effect was bone marrow suppression, observed in 9 patients (69.2%). Adverse effects that seemed to be infusion reaction occurred in 4 patients (30.7%). These adverse effects related to infusion reaction disappeared by reducing or stopping rituximab. Four (30.7%) patients died and 3 of those died due to disease progression. One of those died 1.5 month after he began chemotherapy and the cause of death was unknown. CONCLUSION: This result suggested that both CHOP and THP-COP combined with rituximab were safe and effective for old-old and extremely old patients.

[A case of anaplastic large cell lymphoma associated with Epstein-Barr virus infection, representing clinicopathological features of malignant histiocytosis].

An 82-year-old woman was admitted with fever and anorexia. Aggravated pancytopenia and liver dysfunction suggested the presence of disseminated intravascular coagulation. The serum ferritin level increased to 9,100 ng/ml. Bone marrow aspiration showed an increase of histiocytes with phagocytosis and a diagnosis of hemophagocytic syndrome was made. Symptomatic therapy was performed because of her deteriorated general condition. She died of multiple organ failure, 32 days after admission. Autopsy revealed swollen lymph nodes with proliferation of large neoplastic cells containing rich cytoplasm and pleomorphic and multi-segmented large nuclei. The immunophenotype of the neoplastic cells was LCA-, CD3-, CD5-, CD 20-, CD79a-, UCHL1-, MT1-, CD15-, p80-. Neoplastic cells were positive for CD30, mainly in Golgi apparati, and also positive for EBV-encoded small nonpolyadenylated RNAs (EBER). This case was diagnosed as anaplastic large cell lymphoma (ALCL) associated with hemophagocytic syndrome. It was estimated that Epstein-Barr virus had played an important role in the development of ALCL in the present case.