[Serum sickness induced by rituximab infusion; report of two cases with hematological malignancies].

We report 2 cases of serum sickness after rituximab infusion. Case 1 is a patient with Waldenström's macroglobulinemia, and case 2 is a patient with marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and Sjögren's syndrome. Both patients had polyclonal hypergammaglobulinemia, were treated with rituximab monotherapy, developed serum sickness between 9 and 17 days after the first rituximab infusion, developed fever and arthralgia, and improved soon after corticosteroid treatment. Serum sickness after rituximab treatment for hematological malignancies is very rare as far as we know. We identified three risk factors of serum sickness after rituximab infusion from previous reports and our cases; administration of rituximab alone, the existence of Sjögren's syndrome, and polyclonal hypergammaglobulinemia.

Chemotherapy using hybrid liposomes along with induction of apoptosis.

We have produced hybrid liposomes (HL) which can be prepared by ultrasonicating a mixture of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(23)dodecyl ether in a buffer solution. The fifty-percent inhibitory concentration (IC50) of HL on the growth of human B lymphoma (RAJI) cells in vitro was determined. The IC50 of HL on the growth of RAJI cells was one half of that of DMPC liposomes. Induction of apoptosis by HL in RAJI cells was verified on the basis of flow cytometric analysis, agarose gel electrophoresis and fluorescence microscopy. Apoptotic DNA was observed in RAJI cells treated with HL. Fluorescence micrographs of RAJI cells after adding HL indicated the induction of apoptosis. The therapeutic effects of HL in vivo were examined using SCID mice inoculated with RAJI cells. Markedly prolonged survival of mice was obtained after treatment with HL. No adverse effects were observed in normal rats in toxicity tests carried out with HL. Clinical applications of HL for patients were examined after the approval of the Bioethics Committee. Remarkable reduction of a solid tumor and prolonged survival for one patient with advanced lymphoma were attained after treatment using HL. Chemotherapy with drug-free HL was established without any side effects for the first time.

Successful treatment of bulky granulocytic sarcoma of the retroperitoneum with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

Granulocytic sarcoma is a rare disease that is rarely curable with conventional chemotherapy. This report describes a case of a patient with bulky granulocytic sarcoma of the retroperitoneum who was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation without administering granulocyte colony-stimulating factor before stem cell collection. According to bone marrow assessment and imaging studies, the patient remained in complete remission at 5 years after transplantation. This case suggests that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation is a therapeutic option for granulocytic sarcoma.

Glucocorticoid Therapy and the Risk of Infection in Patients With Newly Diagnosed Autoimmune Disease.

Glucocorticoid (GC) therapy is associated with the risk of life-threatening adverse events in patients with autoimmune disease. To determine accurately the incidence and predictors of GC-related adverse events during initial GC treatment, we conducted a cohort study. Patients with autoimmune disease who were initially treated with GCs in Japan National Hospital Organization (NHO) hospitals were enrolled. Cox proportional hazard regression was used to determine the independent risks for GC-related serious adverse events and mortality. Survival was analyzed according to the Kaplan-Meier method and was assessed with the log-rank test.The 604 patients had a total follow-up of 1105.8 person-years (mean, 1.9 year per patient). One hundred thirty-six patients had at least 1 infection with objective confirmation, and 71 patients had serious infections. Twenty-two cardiovascular events, 55 cases of diabetes, 30 fractures, 23 steroid psychosis events, and 4 avascular bone necrosis events occurred during the follow-up period. The incidence of serious infections was 114.8 (95% confidence interval, 95.7-136.6) per 1000 person-years. After adjustment for covariates, the following independent risk factors for serious infection were found: elderly age (hazard ratio [HR], 1.25/10-yr age increment; p = 0.016), presence of interstitial lung disease (HR, 2.01; p = 0.011), high-dose GC use (≥29.9 mg/d) (HR, 1.71; p = 0.047), and low performance status (Karnofsky score, HR, 0.98/1-score increment; p = 0.002). During the follow-up period, 73 patients died, 35 of whom died of infection. Similarly, elderly age, the presence of interstitial lung disease, and high-dose GC use were found to be significant independent risk factors for mortality. The incidence of serious and life-threatening infection was higher in patients with autoimmune disease who were initially treated with GCs. Although the primary diseases are important confounding factors, elderly age, male sex, the presence of interstitial lung diseases, high-dose GCs, and low performance status were shown to be risk factors for serious infection and mortality.

Rates of serious intracellular infections in autoimmune disease patients receiving initial glucocorticoid therapy.

BACKGROUND/AIMS: The Japanese National Hospital Organization evidence-based medicine (EBM) Study group for Adverse effects of Corticosteroid therapy (J-NHOSAC) is a Japanese hospital-based cohort study investigating the safety of the initial use of glucocorticoids (GCs) in patients with newly diagnosed autoimmune diseases. Using the J-NHOSAC registry, the purpose of this observational study is to analyse the rates, characteristics and associated risk factors of intracellular infections in patients with newly diagnosed autoimmune diseases who were initially treated with GCs. METHODOLOGY/PRINCIPAL FINDINGS: A total 604 patients with newly diagnosed autoimmune diseases treated with GCs were enrolled in this registry between April 2007 and March 2009. Cox proportional-hazards regression was used to determine independent risk factors for serious intracellular infections with covariates including sex, age, co-morbidity, laboratory data, use of immunosuppressants and dose of GCs. Survival was analysed according to the Kaplan-Meier method and was assessed by the log-rank test. There were 127 serious infections, including 43 intracellular infections, during 1105.8 patient-years of follow-up. The 43 serious intracellular infections resulted in 8 deaths. After adjustment for covariates, diabetes (Odds ratio [OR]: 2.5, 95% confidence interval [95% CI] 1.1-5.9), lymphocytopenia (≦1000/µl, OR: 2.5, 95% CI 1.2-5.2) and use of high-dose (≧30 mg/day) GCs (OR: 2.4, 95% CI 1.1-5.3) increased the risk of intracellular infections. Survival curves showed lower intracellular infection-free survival rate in patients with diabetes, lymphocytopaenia and high-dose GCs treatments. CONCLUSIONS/SIGNIFICANCE: Patients with newly diagnosed autoimmune diseases were at high risk of developing intracellular infection during initial treatment with GCs. Our findings provide background data on the risk of intracellular infections of patients with autoimmune diseases. Clinicians showed remain vigilant for intracellular infections in patients with autoimmune diseases who are treated with GCs.

The absence of the p15INK4B gene alterations in adult patients with precursor B-cell acute lymphoblastic leukaemia is a favourable prognostic factor.

We examined deletion and methylation of the p15INK4B (p15) and p16INK4A (p16) genes, using Southern blotting and methylation-specific polymerase chain reaction (PCR), in 70 untreated adult patients with precursor B-cell acute lymphoblastic leukaemia (PBC-ALL) and analysed the relationship between their genetic changes and clinical outcome. Methylation and homozygous deletion of the p15 gene were detected in 30 (43%) and 18 (26%) patients, while those of the p16 gene were found in 16 (23%) and 11 (16%) patients respectively. Thirteen out of 17 patients with wild-type p15 gene showed expression of p15 mRNA, whereas 31 out of 39 patients with alteration (deletion and methylation) of the p15 gene showed no p15 mRNA expression by reverse transcription-PCR, suggesting that alterations of the p15 gene are highly associated with loss of p15 mRNA expression. Disease-free survival (DFS) at 4 years in patients with wild-type p15 gene is 33%, compared with 4% of those with p15 gene alterations (P = 0.049). Multivariate analysis showed that the absence of p15 gene alterations was an independent significant favourable prognostic factor for longer DFS (P = 0.0001). These results suggest that alterations in the p15 but not p16 gene can be used as a genetic prognostic indicator in PBC-ALL.