R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma.

Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.

Concentrated ascites reinfusion therapy for sinusoidal obstructive syndrome after hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is one of the severe complications of hematopoietic stem cell transplantation (HSCT). Systemic management including respiratory and circulatory support is necessary. In addition, abdominal paracentesis is often needed for pain relief and to reduce the pressure of tense ascites. Concentrated ascites reinfusion therapy (CART) involves the filtration, concentration, and reinfusion of drained ascites, which contributes to reuse of autologous proteins. CART has been reported as supportive therapy for patients with liver cirrhosis and cancer. We retrospectively reviewed the efficacy and safety of CART in three patients (two with acute myelogenous leukemia and one with chronic myeloid leukemia) who developed SOS after allo-HSCT. They all had symptomatic, tense, and diuretic-refractory ascites with right costal pain and marked weight gain. Two patients showed immediate improvement after CART. However, one patient experienced four CARTs with slow recovery. All patients are now alive and are being monitored as outpatients over 2 years with remission. No severe adverse event was observed related to CART, and 25.2-98.0 (median 30.2) grams of albumin was collected and reinfused. CART after paracentesis reduces protein loss in ascites by reinfusion of autologous protein instead of exogenous albumin preparations. Although transient fever is reported as a frequent adverse event, no events like severe bleeding or infection were observed. While its safety has not been fully established in patients with hematological disease after HSCT, CART may be a considerable supportive therapy for SOS with tense ascites.

Long-term outcome of human herpesvirus-6 encephalitis after allogeneic stem cell transplantation.

Human herpesvirus-6 (HHV-6) encephalitis is recognized as a relatively rare, but sometimes lethal, complication of allogeneic hematopoietic stem cell transplantation (HSCT). Although the development of new diagnostic techniques and antiviral therapy has improved, the prognosis of encephalitis is still unclear. We surveyed 197 patients who underwent allogeneic HSCT between January 2004 and March 2008 at our institution, and 8 (4.0%) were diagnosed as having HHV-6 encephalitis. Five were male and 3 were female, with a median age of 40.5 years. The median onset of HHV-6 encephalitis was 18 days after HSCT, and the median duration of antiviral therapy was 41 days. The median survival time from the onset of encephalitis was 23.1 months (range: 2.7-66.7), and 3 patients died of unrelated causes (sepsis in 2 and gastrointestinal tract bleeding in 1). Cord blood transplantation was identified as the only independent risk factor (relative risk [RR] = 4.98; P = .049) by multivariate analysis. There was no statistical significance of survival after HSCT between the patients with HHV-6 encephalitis and those without HHV-6 encephalitis (the 2-year survival rate was 60% and 52.6%, respectively; P = .617). Four of the 5 surviving patients were unable to return to society because of neuropsychological disorders, including anterograde amnesia and seizures with prominent hippocampal atrophy. Although HHV-6 encephalitis occurring after HSCT is now becoming a curable complication, its sequelae, such as neuropsychological disorders, have a marked influence on the quality of life of long-term survivors. Accordingly, it is necessary to identify risk factors for HHV-6 encephalitis and establish methods for prevention of this complication.

The therapeutic effect of rituximab on CD5-positive and CD5-negative diffuse large B-cell lymphoma.

The prognosis of diffuse large B-cell lymphoma (DLBCL) has improved markedly in recent years of rituximab era. The prognosis of de novo CD5-positive DLBCL is reported to be poor, but the effect of rituximab on this type of lymphoma remains unclear. To investigate the effect of rituximab on CD5-positive DLBCL, we collected DLBCL patients and analysed prognostic factors. A total of 157 patients with DLBCL who were immunophenotyped with flow-cytometry (FCM) and treated with chemotherapy were subjected to analysis. Those treated with radiotherapy alone or with supportive therapy only were not included. Patients diagnosed in 2003 or later were treated with rituximab combined chemotherapy. There were 95 males and 62 females. Their age ranged from 20 to 91 years old, and the median was 65 years. Nineteen patients were diagnosed as having de novo CD5-positive DLBCL. Rituximab was given alongside chemotherapy in 85 patients. Of these, 11 were positive for CD5 and 74 were negative. The addition of rituximab improved the overall survival (OS) of DLBCL patients (2-year OS: 82% vs. 70%, p = 0.01). For CD5-negative DLBCL, patients treated with rituximab showed 2-year OS of 84%, which was significantly better than those treated without rituximab (70%, p = 0.008). However, for CD5-positive DLBCL, the prognosis was not statistically different between the patients treated with and without rituximab (59% vs. 50%, p = 0.72). Although rituximab improved the prognosis of DLBCL, such improvement was restricted to the CD5-negative group. Further investigation is required to improve the prognosis of patients with CD5-positive DLBCL.

Features of primary extranodal lymphoma in Kanagawa, a human T-cell leukemia virus type 1 nonendemic area in Japan.

We sought to determine the frequency of primary extranodal lymphoma (ENL) and its characteristics in Kanagawa, a human T-cell leukemia virus type 1 (HTLV-1) nonendemic area in Japan. Subjects were 847 newly diagnosed patients with malignant lymphoma at the Yokohama City University Hospital and 8 affiliated hospitals mainly located in Kanagawa prefecture from 1999 to 2005. We compared the clinicopathological characteristics of primary ENL with primary nodal lymphoma (NL). Histological specimens were evaluated according to the World Health Organization classifications. A total of 395 (46.6%) and 452 (53.4%) patients had primary ENL and primary NL, respectively. The frequency of primary ENL increased with age. Primary extranodal sites included the gastrointestinal tract (30.4%), Waldeyer's ring (17.8%), orbits (7.0%), soft tissue and subcutaneous tissue (5.2%), bone (4.6%), skin (4.3%), thyroid gland (4.3%), testis and prostate (3.3%), bone marrow (3.3%), nasal and paranasal cavities (2.6%), salivary glands (2.3%), lung and pleura (2.0%), breast (1.8%), central nervous system (1.0%), uterus and ovary (0.5%), and others (9.8%). Among the 395 cases of primary ENL, diffuse large B-cell lymphoma (61.2%) was most frequently diagnosed, followed by extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (13.3%) and follicular lymphoma (5.6%). The frequency of primary ENL is approximately 50% of the total lymphoma cases in Kanagawa, an HTLV-1 nonendemic area in Japan. This frequency appears to be higher than that in Western countries.

[Discrepant results of ABO type of red cells and serum in a patient with acute myelogenous leukemia].

A 42-year-old woman was admitted to our hospital with acute myelogenous leukemia. We conducted blood-type examination, and her serum showed strong agglutination with all B cells but questionable agglutination with A1 cells, which became stronger with incubation. We considered her blood type as O, but her previously assessed blood type was A. After receiving one cycle of induction therapy, she achieved complete remission and blood group A antigen was proven on her red blood cells. Anti-A1 in her serum disappeared after induction therapy. We should be aware that blood group antigens are not entirely independent of the environment and are occasionally modified by disease.

The increased ratio of 11ß-hydroxysteroid dehydrogenase type 1 versus 11ß-hydroxysteroid dehydrogenase type 2 in chronic periodontitis irrespective of obesity.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive cortisone to active cortisol, has been reported to play an important role in metabolic diseases as well as chronic inflammatory diseases. The involvement of 11ß-HSD1 in chronic periodontitis was investigated in the present study. The relationship between the levels of 11ß-HSD1, chronic periodontitis, and body mass index (BMI) was analyzed. The expression of 11ß-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the control group. Since the expression of 11ß-HSD2, which converts active cortisol to inactive cortisone, was slightly lower in the chronic periodontitis group than in the controls, the ratio of 11ß-HSD1 versus 11ß-HSD2 was significantly higher in the chronic periodontitis group than in the controls. A correlation was not observed between BMI and the level of 11ß-HSD1 or between BMI and the ratio of 11ß-HSD1 versus 11ß-HSD2. These results suggested that an increase in the ratio of 11ß-HSD1 versus 11ß-HSD2 was associated with chronic periodontitis irrespective of obesity.

A human T-cell lymphotropic virus type-1 (HTLV-1) carrier complicated with various autoimmune diseases including primary biliary cirrhosis.

A 47-year-old woman with primary biliary cirrhosis and scleroderma was examined at our hospital for a 1-week history of non-resolving fever, arthralgia, myalgia, muscle weakness and fatigue. A diagnosis of systemic lupus erythematosus was made based on arthralgia, low leukocyte count, low lymphocyte count, low serum concentration of complements, positive anti-nuclear antibody and positive anti-double-strand-DNA antibody. She was negative for anti-U1RNP antibody, but positive for anti-Jo1 antibody, and her initial serum concentration of creatine phosphokinase was elevated. We diagnosed her as having overlap syndrome with scleroderma, systemic lupus erythematosus and possible polymyositis associated with primary biliary cirrhosis. Prednisolone rapidly improved her symptoms. Lobulated leukocytes were observed in her peripheral blood specimen. She was positive for anti-HTLV-1 antibody, but Southern blot hybridization did not confirm monoclonal integration of HTLV-I proviral DNA in her peripheral blood. This suggests the possibility of a relationship between HTLV-1 infection and various autoimmune disorders including primary biliary cirrhosis.

[The VF-14 index of functional visual impairment in patients with corneal disease treated by phototherapeutic keratectomy].

PURPOSE: To evaluate the Visual Function 14(VF-14) index of functional visual impairment in patients with corneal disease treated by phototherapeutic keratectomy (PTK). METHODS: Seventy-two patients with corneal disease who were treated by PTK participated in this study between March 1999 and September 2002. Demographic, ocular history, best-corrected visual acuity, and detailed ocular examination data were collected. Functional visual impairment information was obtained by questionnaire covering the following: VF-14, Cataract Symptom Score, and satisfaction with vision. RESULTS: The mean best-corrected visual acuity of the eye scheduled for PTK was 0.67+/-0.63(mean +/- standard deviation) the logarithm of the minimum angle resolution (logMAR) whereas that of the post-operated eye was 0.34+/-0.38 logMAR. The mean VF-14 score, Cataract Symptom Score, and satisfaction with vision were improved significantly after the treatment. The satisfaction with vision was correlated with the VF-14 score and the Cataract Symptom Score. The VF-14 scores of all of the patients whose pre-PTK VF-14 scores were under 50 were improved after PTK. CONCLUSIONS: The VF-14 is a valid measure of functional visual impairment in patients with corneal disease treated by PTK.

Methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections in the cornea.

PURPOSE: To describe the incidence and clinical management of corneal infections with methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). METHODS: The incidence of methicillin-resistant Staphylococcus (MRS) at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, was reviewed during the 5-year period from January 1996 to December 2000. Clinical aspects of MRS colonization or infection in the eye were investigated. RESULTS: Methicillin-resistant S. aureus or MRSE was detected from 30 eyes with ocular diseases; post-keratoplasty (11 eyes), ocular surface disorders without operation (9 eyes), and others (10 eyes). Among the 30 eyes, 12 manifested keratitis. Eight cases (8 eyes) occurred after keratoplasty, including four postoperative cases in patients with Stevens-Johnson syndrome, and two bilateral cases (4 eyes) in patients with acute-phase Stevens-Johnson syndrome. The degree of MRS keratitis was classified into 4 groups: asymptomatic carrier or conjunctivitis, intraepithelial infiltrations, superficial keratitis, and severe keratitis leading to corneal perforation. All cases of keratitis were treated successfully with topical ofloxacin (OFLX), vancomycin (VCM), or arbekacin (ABK). CONCLUSION: Factors associated with ocular MRS colonization were long-term use of antibiotics and/or steroids, and hospitalization. Patients who had undergone keratoplasty or who had Stevens-Johnson syndrome were at increased risk of MRS keratitis. Superficial stromal infiltrations, minimal melting, and minimal stromal scarring are characteristic of MRS keratitis. Therapy for MRS keratitis is summarized. Ofloxacin, VCM, and ABK are effective in the treatment of MRS keratitis. Vancomycin eye ointment is effective as the final choice in serious cases.

Upfront autologous stem cell transplantation for untreated high-risk diffuse large B-cell lymphoma in patients up to 60 years of age.

BACKGROUND: Although rituximab added to CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) is the standard chemotherapy for untreated DLBCL, its therapeutic effect is limited in younger patients with high-intermediate risk or high-risk disease according to the age-adjusted international prognostic index. In fact, the efficacy and safety of HDT plus rituximab followed by ASCT for such patients remain unclear. PATIENTS AND METHODS: We retrospectively investigated the safety and effectiveness of HDT/ASCT in patients with untreated DLBCL. Twenty-two patients, aged 60 years and younger, with untreated DLBCL (classified as high-intermediate [n = 14 (64%)] or high [n = 8 (32%)] risk) underwent upfront HDT/ASCT between January 2004 and December 2008, achieving either a complete response (CR; n = 15 (68%)) or a partial response (PR; n = 7 (32%)). RESULTS: The 5-year overall survival rate was 81.0% and the progression-free survival rate was 73.0%, with no significant difference between risk groups based on the international prognostic index. The most common nonhematologic toxicity was febrile neutropenia [n = 9 (41%)]. The cause of all 3 fatalities was exacerbation of the underlying disease, and no treatment-related mortality was observed. No variables with a significant influence on overall survival were identified, but a correlation of the treatment response before transplanation with progression-free survival was suggested (CR vs. PR: 92% vs. 30%, P = .002). CONCLUSION: These results suggest that adding rituximab to upfront HDT/ASCT is feasible and can improve the outcome in untreated patients with poor-prognosis DLBCL. In the future, upfront HDT/ASCT should be more extensively evaluated in clinical trials.

Absolute monocyte count in follicular lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Elevated absolute monocyte counts (AMCs) have been reported to indicate poor prognosis for patients with lymphoproliferative disease, including those with follicular lymphoma (FL) receiving various treatments. We evaluated the prognostic impact of AMC in 150 consecutive FL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Progression-free survival (PFS) did not differ significantly according to the AMC level. Univariate and multivariate analyses did not indicate a prognostic significance of AMC for PFS. Thus, the AMC is not a prognostic factor for FL patients treated with R-CHOP. However, immunochemotherapy might influence the prognostic impact of AMC.

Clinical significance of minimal residual disease detected by multidimensional flow cytometry: serial monitoring after allogeneic stem cell transplantation for acute leukemia.

We analyzed minimal residual disease (MRD) by multidimensional flow cytometry (MFC) after allogeneic stem cell transplantation in 41 patients with acute myeloid leukemia (AML) (n=31) or acute lymphoblastic leukemia (ALL) (n=10). Aberrant antigen expression was compared with the results of quantitative PCR for WT1 mRNA (n=41) and leukemia-specific fusion transcripts (n=12; AML in seven, ALL in five). There was a significant correlation between detection of MRD by MFC and WT1 mRNA, as well as between MFC and fusion transcripts. Serial monitoring of MRD by the three techniques correlated in parallel to the clinical course in most of the patients, but three patients were only positive for WT1 during hematological remission. The overall survival time of patients with complete remission was significantly associated with the appearance of aberrant expression after transplantation. In conclusion, MFC is valuable for clinical management decisions after transplantation.

Ocular surface molecule after transconjunctival vitrectomy.

AIM: To evaluate ocular surface molecules after transconjunctival pars plana vitrectomy (PPV). METHODS: A total of 28 eyes of 28 patients who received PPV were examined. Tears (10µl) were collected before and after 20-gauge PPV or 23-gauge PPV. The concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factor (TNF)-α were measured. The concentrations of each cytokine before and after surgery were compared. The change ratios of each cytokine (post-/presurgery) between 20-gauge and 23-gauge PPV were compared. RESULTS: IL-1ß, IL-6, IL-8 increased after PPV (Wilcoxon rank sum test; IL-1 ß, p=0.009; IL-6, p<0.001; IL-8, p<0.001), while the other cytokines did not. Among them, only IL-8 increased significantly in 20-gauge PPV than in 23-gauge PPV (p=0.01, Mann-Whitney U test). Multivariate analysis showed that 20-gauge PPV was a significant factor behind the increase in postoperative IL-8 (OR 5.21, 95% CI (1.46 to 18.55), p=0.018), but surgical time and simultaneous cataract surgery were not significant factors. CONCLUSIONS: The increase in inflammatory cytokine IL-8 in tear was significantly less after 23-gauge PPV than 20-gauge PPV, indicating that transconjunctival PPV is less invasive from the viewpoint of the ocular surface molecular biology. This information may be important when deciding the method of PPV.

A retrospective analysis of obstetric patients with idiopathic thrombocytopenic purpura: a single center study.

Idiopathic thrombocytopenic purpura (ITP) commonly affects women of childbearing age. We studied the clinical characteristics of pregnant women with ITP to estimate their risks of bleeding. A retrospective chart review was performed for all obstetric patients with ITP who had delivery at our hospital, from 1 March 2000 to 31 March 2008. Twenty women with ITP delivered 24 children in 23 pregnancies. In all, eight women were treated with corticosteroid during their pregnancy period, and there was only one non-responder. There was no correlation between the maternal platelet count and the amount of blood loss at delivery. Two infants were revealed to have had platelet counts lower than 30 × 109/L, and were treated with high-dose IV IgG. One of them also received corticosteroid therapy. There was no relationship between maternal platelet count at delivery and infant platelet count at birth. Overall, no serious bleeding event was seen in either of the mothers or infants. For most women with ITP, pregnancy is uncomplicated, and even those with severe thrombocytopenia during pregnancy have good outcomes when under the strict care of a hematologist and gynecologist.