Development of acquired hemophilia A during treatment of multiple myeloma with lenalidomide.

We describe a 67-year-old female demonstrating symptomatic multiple myeloma (MM) with anemia and bone lesions initially diagnosed in 2009. Although a partial response was achieved after bortezomib and dexamethasone treatment, MM recurred in 2012. Therefore, treatment with lenalidomide, cyclophosphamide, and dexamethasone was commenced. Coagulation tests conducted prior to the chemotherapy were normal. Lenalidomide was discontinued after 10 days due to exacerbation of renal dysfunction. Simultaneously, activated partial thromboplastin time (APTT) was prolonged to 89.5 seconds. The mixing test showed an inhibitor pattern, with factor VIII at 2% and factor VIII inhibitor at 4.85 BU/ml. A diagnosis of acquired hemophilia A was made, and treatment with prednisolone was started, after which APTT improved to 36.4 seconds and factor VIII inhibitor decreased to 1.09 BU/ml. The factor VIII inhibitor level again increased concomitantly with restarting lenalidomide, which was, therefore, discontinued, while immunosuppressive therapy was administered with the addition of cyclophosphamide. Factor VIII inhibitor gradually disappeared from the patient's blood over the next four months. To the best of our knowledge, this is the first description of lenalidomide as a possible cause of acquired hemophilia A. Our experience indicates that we need to pay attention to acquired hemophilia A after initiating lenalidomide therapy in patients with hematologic malignancies.

[Hypofibrinogenemia associated with steroid therapy for the patients who developed GVHD after allogeneic stem cell transplantation].

Hypofibrinogenemia (plasma fibrinogen level <150 mg/dl) is occasionally observed after allogeneic hematopoietic stem cell transplantation, and its etiology is often difficult to determine. We herein report that steroids administered for the treatment of graft-versus-host disease (GVHD) are associated with the development of hypofibrinogenemia. We retrospectively analyzed the plasma fibrinogen (Fg) levels in 15 consecutive patients who had been administered 1 mg/kg/day (1 mg/kg group) or 2 mg/kg/day (2 mg/kg group) methylprednisolone for the treatment of Grade II to IV acute GVHD. Hypofibrinogenemia had developed in 8 of the 15 patients (53%) by day 50 after the start of steroid treatment, and was observed in 2 of 6 patients in the 1 mg/kg group and 6 of 9 in the 2 mg/kg group. A significant decrease in the Fg level was observed in the 2 mg/kg group (the median value before starting steroid treatment and that on the 20th day after starting steroid treatment were 506 mg/dl and 180 mg/dl, respectively, P=0.0013). Other possible causes of hypofibrinogenemia, including liver dysfunction or disseminated intravascular coagulation, were confirmed in only 3 patients during the observation period. In conclusion, hypofibrinogenemia commonly occurs in patients treated with steroids, especially those administered 2 mg/kg/day methylprednisolone for the treatment of GVHD.

[Retrospective analysis of thalidomide therapy in patients with relapsed/refractory multiple myeloma].

Thalidomide is now recognized as an important agent for multiple myeloma. In this study, we retrospectively analyzed the effect of thalidomide therapy in 52 patients with relapsed/refractory multiple myeloma. Median age was 70 years. Eight patients were treated with thalidomide alone, 36 with dexamethasone, and 8 with chemotherapy. The maintenance dose of thalidomide was 100 mg/day in 42 cases. The probability of overall survival and progression-free survival one year after the start of thalidomide were 76.2% and 70.9%, respectively. Complete or partial response was obtained in 16 patients (31%). The probability of survival was better in patients who obtained a partial or complete response than in non-responders (P=0.04). Adverse effects (CTCAE criteria Grade 3-4) were somnolence (n=3), constipation (n=5), peripheral neuropathy (n=1), deep vein thrombosis (n=1), anemia (n=10), leukocytopenia (n=10), and thrombocytopenia (n=3). The high incidence of cytopenia in this study suggests that the Japanese population tends to display bone marrow suppression after thalidomide therapy. Some patients developed peripheral neuropathy at the early stage of administration and attention was necessary. In conclusion, thalidomide therapy is safe and effective in patients with refractory multiple myeloma.

Antiobesity and Anti-Inflammatory Effects of Orally Administered Bonito Extracts on Mice Fed a High-Fat Diet.

BACKGROUND: The condensed fermentative extract of bonito (BoE), skipjack tuna (Katsuwonus pelamis), has claimed its health conditioning effects against lifestyle-related diseases such as hypertension and type 2 diabetes. METHODS: We evaluated the antiobesity and anti-inflammatory effects of BoE on mice fed a high-fat diet (HFD). Mice (9 weeks of age) were maintained for 11 weeks on HFD with or without BoE (50 mg or 500 mg/kg). RESULTS: Compared with untreated mice, BoE50 or BoE500 mice achieved maximum weight reductions of 7.4% (males) and 11.4% (females), and visceral fat in male BoE500 mice was more decreased among all mice (P = 0.00459). Furthermore, an antiobesity gene uncoupling protein-1 was significantly induced in the visceral fat tissues of male BoE500 (P = 0.0110) and female BoE50 and BoE500 mice (P = 0.0110 and P = 0.0110, resp.). Finally, we detected reduced amount of granulocyte-colony stimulating factor (P = 0.0250) in the sera of female BoE50 and interleukin- (IL-) 5 (P = 0.0120), IL-6 (P = 0.0118), and IL-13 (P = 0.0243) in female BoE500 mice. CONCLUSION: The antiobesity and anti-inflammatory effects of BoE were demonstrated with our examination system and any toxic adverse effects were not observed in mice during the 3-month investigation.

Two Elderly Patients with Philadelphia Chromosome Positive Mixed Phenotype Acute Leukemia Who Were Successfully Treated with Dasatinib and Prednisolone.

Philadelphia chromosome positive (Ph+) mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia having both myeloid and lymphoid features for which no optimal treatment has yet been established. We herein describe two elderly Ph+MPAL patients who achieved molecular remission without any serious adverse events by treatment with dasatinib and prednisolone. Although dasatinib induction therapy combined with prednisolone is known to be a highly effective treatment for Ph+ acute lymphoblastic leukemia, its efficacy for Ph+MPAL has not been shown. The clinical courses of the present cases suggest that combination therapy with dasatinib and prednisolone is a safe and effective therapeutic modality in elderly Ph+MPAL patients.

Toxoplasmic Encephalitis with Untreated Hairy Cell Leukemia Variant.

Toxoplasmic encephalitis is a rare infectious complication in patients with hematological malignancy except for allogeneic hematopoietic stem cell transplantation (HSCT). We herein report a case of possible toxoplasmic encephalitis with untreated hairy cell leukemia variant. Magnetic resonance imaging showed multiple nodules with surrounding edema in the entire cerebrum. A polymerase chain reaction analysis for Toxoplasma gondii was negative. Her signs and symptoms fully recovered by empirical therapy with sulfadiazine and pyrimethamine. Toxoplasmic encephalitis may occur in patients who undergo non-allogeneic HSCT for hematological malignancies, even in those who have not been treated.

Rare primary effusion lymphoma associated with HHV-8 in Japan.

We describe a 62-year-old man infected with human immunodeficiency virus (HIV)-1 who developed primary effusion lymphoma (PEL). Pleural effusion contained atypical lymphoid cells with human herpesvirus (HHV)-8 latent nuclear antigen (LANA)(+). Radiological examination revealed pleural and pericardial effusion, but no evidence of tumor mass or lymph node enlargement. The patient was administered with highly active anti retroviral therapy (HAART) and THP-COP therapy, resulting in complete remission. The prevalence of HHV-8 infection among HIV positive individuals is higher than in the general population in Japan. Although PEL is extremely rare in Japan, the incidence might increase in the future.

Successful treatment of refractory enteropathy-associated T-cell lymphoma using high-dose chemotherapy and autologous stem cell transplantation.

A 65-year-old woman presented with a 6-month history of abdominal pain and watery diarrhea. Type II enteropathy-associated T-cell lymphoma (EATL) was diagnosed based on the clinical presentation and pathological examination of the tumor. The patient received combination chemotherapy but did not achieve remission. Subsequently, high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) were performed. After these therapies, she achieved complete remission, which has been sustained for 18 months. Although the role of HDT-ASCT for EATL is still controversial, the clinical course of this patient suggests that ASCT can improve the prognosis in some patients with EATL.