Association between frailty and bone loss in patients undergoing maintenance hemodialysis.

Frailty is significantly associated with bone loss in the general population. However, it is unclear whether this association also exists in patients undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to assess the association between frailty and bone loss in patients undergoing hemodialysis. This cross-sectional study included 214 (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis three times per week, with a mean age of 67.1 years (women) and 66.8 years (men). Frailty was defined based on criteria set forth by the Cardiovascular Health Study (CHS)-19 (21.1%) women and 47 (37.9%) men were robust, 41 (45.6%) women and 43 (34.7%) men were pre-frail, and 30 (33.3%) women and 34 (27.4%) men were frail. For bone mass, quantitative ultrasound (QUS) parameters (speed of sound, broadband ultrasound attenuation, stiffness index) of the calcaneus were measured. The association between frailty and QUS parameters was determined separately for women and men using multivariate analysis of covariance (ANCOVA), with adjustments for clinical characteristics including age, body mass index, hemodialysis vintage, diabetes, current smoking, serum albumin, phosphate, corrected calcium, intact parathyroid hormone, and medication for CKD-MBD (vitamin D receptor activator, calcimimetics). ANCOVA revealed that all QUS parameters declined significantly with increasing levels of frailty in both sexes (P < 0.05). In conclusion, frailty (as defined by CHS criteria) should be considered a risk factor for bone loss in patients undergoing hemodialysis.

A phase II study of rituximab combined with pirarubicin-cyclophosphamide, vincristine and prednisolone regimen as first-line therapy for patients with indolent B-cell lymphoma.

The anthracycline drug pirarubicin (tetrahydropyranyl-adriamycin [THP]) apparently has been reported to show fewer cardiotoxic effects than doxorubicin. We have previously described the effectiveness of the R-THP-COP regimen comprising rituximab, cyclophosphamide, pirarubicin, vincristine and prednisolone in patients with diffuse large B-cell lymphoma. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) for patients with previously untreated advanced-stage indolent CD20-positive B-cell lymphoma according to the Working Formulation and World Health Organization classification. Four to six courses of the regimen were administered every 3 weeks in 50 patients. The complete remission rate was 57%, while the 3-year overall survival rate was 92%. Regimen-related death was not observed. The R-THP-COP regimen appears very effective for patients with previously untreated advanced-stage indolent CD20-positive B-cell lymphoma. The present results indicate the need for randomized trials of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) and R-THP-COP among patients with CD20-positive indolent lymphoma.

Phase II study of the tetrahydropyranyl adriamycin-cyclophosphamide, vincristine, and prednisolone regimen combined with rituximab as first-line treatment for elderly patients with diffuse large B-cell lymphoma.

The anthracycline drug pirarubicin (tetrahydropyranyl adriamycin; THP) apparently has fewer cardiotoxic effects than doxorubicin. We previously described the benefit of the THP-COP regimen comprising cyclophosphamide, THP, vincristine, and prednisolone for elderly patients with diffuse large B-cell lymphoma (DLBCL). However, that study was completed before rituximab (R) was introduced into clinical practice. Here we report a phase II study of the THP-COP regimen combined with R (R-THP-COP) every 3 weeks. The complete response and 3-year overall survival rates was 63% and 53%, respectively, and no deaths were related to the regimen. We conclude that the R-THP-COP regimen is safe and effective for patients with DLBCL. Based on these results, a randomized controlled trial of rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and R-THP-COP as a phase III study is ongoing.

Long-term survival of a patient with splenic angiosarcoma after resection, high-dose chemotherapy, and autologous peripheral blood stem cell transplantation.

A 48-year-old woman was admitted to our hospital in 2003, complaining of weight loss. Complete blood cell count revealed thrombocytopenia. Abdominal CT demonstrated marked splenomegaly. FDG-PET revealed a hot spot in the whole spleen. A splenectomy was performed. Histological examination was typical for angiosarcoma. Adjuvant chemotherapy was given, and high-dose chemotherapy with autologous peripheral blood stem cell transplantation was performed. Thrombocytopenia developed again in 2008. CT scan showed a hepatic tumor. A fine-needle biopsy of the liver revealed the first relapse. Despite hepatic lobectomy, radiofrequency ablations and administration of recombinant interleukin-2, she died from respiratory failure in 2009.

Phase II study of Rituximab combined with THP-COP as first-line therapy for patients younger than 70 years with diffuse large B cell lymphoma.

INTRODUCTION: We previously described the effectiveness of the THP-COP regimen comprising cyclophosphamide, pirarubicin (tetrahydropyranyl adriamycin; THP), vincristine and prednisolone in patients with diffuse large B-cell lymphoma (DLBCL). The anthracycline drug THP was apparently less cardiotoxic than doxorubicin. However, that study was completed before rituximab was introduced into clinical practice. We conducted a phase II study to determine the effectiveness of a regimen incorporating rituximab (R-THP-COP) against DLBCL. PATIENTS: Six to 8 courses of the regimen were administered every 2 weeks in 48 patients who were younger than 70 years. RESULTS: The complete remission rate was 92%, the 3-year overall survival rate was 83% and 3-year progression free survival rate was 74%. No deaths were associated with the treatment regimen. CONCLUSION: We conclude that R-THP-COP regimen is very effective against DLBCL. The results of our study urge randomized trials of R-CHOP and R-THP-COP among patients with CD20+ DLBCL.

Serum soluble Fas level determines clinical outcome of patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP.

INTRODUCTION: We previously reported that serum concentrations of soluble Fas (sFas) predict the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) after treatment with CHOP but without rituximab (R). Here, we investigated whether the role of sFas as a prognostic factor remains valid in the R-CHOP era. PATIENTS: We treated 132 patients with DLBCL between October 1995 and September 2002 (group A: without rituximab), and 75 between December 2002 and March 2007 (group B: with rituximab). The patients received eight cycles of CHOP or THP (tetrahydropyranyl-adriamycin)-COP before September 2002, and R-CHOP or R-THP-COP after October 2002. The distribution of patients according to the International Prognostic Index did not significantly differ between the groups. RESULTS: The 5-year overall survival (OS) rates for patients with sFas levels of > or = 3.0 and <3.0 ng/ml in group A were 19.8 and 61.9% (P < 0.0001), whereas the 3-year OS rates in group B were 54.7 and 92.2% (P < 0.01), respectively. Multivariate analysis using the proportional hazards model revealed that sFas most significantly correlated with overall survival (P < 0.05). CONCLUSION: Serum sFas is thus a useful tool for selecting the appropriate therapeutic strategy for DLBCL.

Serum-soluble interleukin-2 receptor (sIL-2R) is an extremely strong prognostic factor for patients with peripheral T-cell lymphoma, unspecified (PTCL-U).

PURPOSE: The aim of this study was to assess the prognostic factors of peripheral T-cell lymphoma, unspecified (PTCL-U). PATIENTS AND METHODS: We retrospectively analyzed 30 cases fulfilling the criteria of PTCL-U defined by the World Health Organization classification. The patients were treated with 6-8 cycles of a CHOP or THP (pirarubicin)-COP regimen. RESULTS: A high serum sIL-2R level (> or =2,000 U/ml) at onset was associated with a low complete remission rate. Patients with high sIL-2R had significantly lower survival rates (5 year, 15.1%) than those with low sIL-2R (<2,000 U/ml) (100%) (P < 0.005). Factors associated with worse overall survival in a univariate analysis were high sIL-2R (P < 0.005), high age (>60 years) (P < 0.05), poor performance status (P < 0.01) and poor international prognostic index (P < 0.05). No correlation was observed between sIL-2R and other markers. Multivariate analysis showed that only sIL-2R was a prognostic factor for overall survival (P < 0.01). CONCLUSION: The results suggest that a high serum sIL-2R level predicts a poor prognosis in PTCL-U.

Immunoproliferative small intestinal disease with protein loss complicated with duodenal T cell lymphoma during progression.

A 52-year-old man was admitted to our hospital in October 2001 with abdominal pain. Abdominal X-ray indicated a diagnosis of ileus. Histopathological and immunological examination resulted in a diagnosis of immunoproliferative small intestinal disease (IPSID). He was treated with THP-COP therapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone), which resulted in complete remission. Outpatient follow-up revealed hypoalbuminemia in May 2003 and upper gastrointestinal endoscopy showed duodenal mucosal nodularity. He was diagnosed with relapsed IPSID and salvage chemotherapy was started. Follow-up endoscopy confirmed that the therapy was effective, but uncovered another duodenal mucosal nodularity. Immunohistochemical staining revealed T-cell lymphoma. Chemotherapy was discontinued and the patient died in December 2004.

Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony-stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy.

BACKGROUNDS AND OBJECTIVES: The optimal strategy for the management of elderly patients with acute myeloid leukaemia (AML) is still controversial. We previously reported the effectiveness of low dose cytarabine (Ara-C) and etoposide (VP-16) (AV therapy) for those elderly AML patients ineligible for intensive chemotherapy. We initiated the present feasibility study to improve the efficacy by using glanulocyte-colony stimulating factor (G-CSF) with AV therapy (AVG therapy). PATIENTS AND METHODS: The eligibility for enrolment was AML patients according to the World Health Organization (WHO) criteria who were over 60 years of age and who had difficulty in tolerating intensive chemotherapy due to their poor performance status (PS) or some comorbidities. They were given continuous drip infusion of Ara-C (20 mg/body) and VP-16 (50 mg/body) for 7-14 days, and were also simultaneously administered G-CSF (150 microg/m2) once daily. RESULTS: The median age of consecutively enrolled 25 patients was 73 years. Eighteen (72%) patients achieved complete remission (CR). The 1-year overall survival (OS) and the 3-year OS rates were 69% and 22%, respectively. The 1-year disease free survival (DFS) rate in CR patients was 44%. The major regimen related toxicities of grade 3 or 4 were only febrile neutropenia in 15 patients (60%). No regimen-related mortality was observed. CONCLUSION: AVG therapy was therefore found to be an effective and well-tolerated regimen for remission induction in elderly AML patients with poor PS or comorbidity.

Intense exercise induces the degradation of adenine nucleotide and purine nucleotide synthesis via de novo pathway in the rat liver.

The purpose of this study was to investigate the influence of intense exercise on the metabolism of adenine nucleotides in the liver. In the first experiment, to determine the degradation of adenine nucleotides, hepatic adenine nucleotides of rats were labeled by an intraperitoneal administration of 15N-labeled adenine the day before treadmill running to exhaustion. In the second experiment, to determine the de novo synthesis of purine nucleotides after intense exercise, 14C-glycine was intraperitoneally administered to rats performing intense running on a treadmill. In the first experiment, hepatic levels of ATP and total adenine nucleotides showed a reduction immediately after exercise. In contrast, hepatic levels of AMP, adenosine, hypoxanthine and uric acid showed an increase immediately after exercise. The hepatic 15N level continued to decline during the recovery period after exercise. Urinary excretion of 15N-urate was 40% higher in the exercised rats than in the control rats. In the second experiment, the radioactivity of 14C detected in the fraction of hepatic urate and allantoin was approximately 300% higher in the exercised rats than in the control rats. 14C-radioactivity that excreted into urine as urate and allantoin was approximately 200% higher in the exercised rats. Intense exercise led to the degradation of hepatic adenine nucleotides, which were not utilized for the re-synthesis of nucleotide and further degraded to hypoxanthine or uric acid. Intense exercise induced the synthesis of purine nucleotides in the liver via a de novo pathway and these synthesized nucleotides were also degraded to nucleosides and excreted into urine.