Re-appearance of hepatitis B virus following therapy with rituximab for lymphoma is not rare in Japanese patients with past hepatitis B virus infection.

BACKGROUND AND AIM: De novo hepatitis B virus (HBV)-related hepatitis is a well-known fatal complication following chemo-immunosuppressive therapy in patients with past HBV infection (HB surface antigen and serum HBV DNA negative, but HB core antibody and/or HB surface antibody positive). This research was conducted to evaluate the incidence of and clinical features associated with re-appearance of serum HBV DNA following chemo-immunosuppressive therapy in Japanese patients with past HBV infection. METHODS: This is a retrospective review. Forty-five patients with past HBV infection who had received chemo-immunosuppressive therapy for haematological disease were followed up for >6 months, to determine whether the serum test for HBV changed from negative to positive (i.e. re-appearance of serum HBV DNA following chemo-immunosuppressive therapy). RESULTS: Re-appearance of serum HBV DNA was confirmed in five (20.8%) of the 24 patients who had received treatment regimens containing rituximab, but in none of the 21 patients who had not received treatment regimens containing rituximab (P=0.035). The HBV genotype could be determined in four of the five aforementioned patients, and in all four, HBV genotype C, which is the most prevalent genotype in Japan, was identified. CONCLUSION: This research showed that re-appearance of serum HBV DNA is not rare in Japanese patients treated with chemotherapy regimens containing rituximab, and no other factors related to such re-appearance of serum HBV DNA could be identified. Well-designed clinical studies, including immunological and genetic analyses of the host and of the HBV, are required for further elucidation.

Splenic infarction after Epstein-Barr virus infection in a patient with hereditary spherocytosis.

We describe the first patient with hereditary spherocytosis (HS) known to have developed splenic infarction following infectious mononucleosis (IM). An 18-year-old Japanese man was referred to our hospital in November 2004 because of continuous fever and icterus. He had undergone cholecystectomy at the age of 14 years. On patient admission in November 2004, a physical examination showed marked hepatosplenomegaly, icterus, and jaundice. He had a white blood cell count of 14.9 x 10(9)/L with 9.5% atypical lymphocytes, a red blood cell count of 2.93 x 10(12)/L, and a hemoglobin concentration of 7.8 g/dL. Microspherocytes were observed in the patient's peripheral blood smear, and immunoglobulin M antibody to Epstein-Barr virus (EBV) viral capsid antigen was detected. The patient's diagnosis was HS with IM. On day 4 of admission, the patient complained of severe abdominal pain. Abdominal computed tomography scanning revealed findings of splenic infarction. Two months after the occurrence of splenic infarction, a splenectomy was performed. A pathohistologic examination of the resected spleen revealed no evidence of thrombosis or arterial occlusion. We assume that the cause of splenic infarction was insufficient blood flow to oxygenate the entire spleen during the acute enlargement of the spleen.

[Early blastic transformation within a year of imatinib treatment in 2 cases of chronic myeloid leukemia].

We report herein on two rare cases of newly diagnosed chronic myeloid leukemia, which developed early blastic transformation within a year of imatinib treatment. Case 1 is a 22-year-old Japanese female, who underwent gradual blastic transformation with the increase of a resistant clone, which cytogenetically evolved right after she reached complete hematologic remission. Case 2 is a 24-year-old Japanese male, who underwent sudden transformation after 8 months treatment with imatinib mesylate following complete cytogenetic response. Although a sudden blastic transformation is extremely rare, the occurrence of such events even among the low-risk, good responding patients highlights the need for continued, rigorous monitoring by sensitive analysis, such as quantitative PCR. In order to accomplish the early eradication of minimal residual disease, the therapeutic strategy for chronic myeloid leukemia has to be defined in the era of imatinib, considering the application of allogeneic stem cell transplantation, which is currently the only curative treatment.

A case of giardiasis expressing severe systemic symptoms and marked hypereosinophilia.

An 88-year-old Japanese woman was referred to our hospital due to a one-month history of face edema, aphagia, shortness of breath, and skin rush over almost her entire skin. She had no abdominal symptoms. Her peripheral blood count showed a white blood cell (WBC) count of 27.1x10(9)/L with 82.1% eosinophils. Serum non-specific Immunoglobulin E was within a normal range. Soluble interleukin-2 receptor was elevated to 4200U/mL. At first, her eosinophil count was so high that we suspected she had an eosinophilic leukemia or hypereosinophilic syndrome. After admission, cysts of Giardia duodenalis (G. duodenalis) were detected in the patient's feces by microscopic analysis, then she was diagnosed with giardiasis, and 750mg per day of metronidazole was administered for seven days. Her WBC count decreased to 6.0x10(9)/L with 10% eosinophils, and her systemic symptoms improved. At that time her serum IL-5 was within a normal range. A few months later, the patient again complained of skin rush, and G. duodenalis was once again found in her feces. Her serum IL-5 was elevated to 751pg/mL. Metronidazole was administered for two weeks, and her eosinophil count decreased. G. duodenalis is a protozoan parasite, and it is one of the most common waterborne transmission gastrointestinal parasites in the world. G. duodenalis rarely causes hypereosinophilia. To our knowledge, this is the first case report of giardiasis with extreme hypereosinophilia and severe systemic symptoms.

Constitutive activity of nuclear transcription factor kappaB is observed in follicular lymphoma.

Constitutive activity of nuclear transcription factor kappaB (NF-kappaB) is observed in many pathological types of lymphoma that are associated with a poor clinical course. This suggests that NF-kappaB and pathways involving NF-kappaB are possible targets for successfully treating lymphoma. We examined 28 lymph nodes from 28 patients in whom follicular lymphoma was diagnosed from 1996 to 2006 at our institution, which were formalin-fixed and paraffin-embedded. The specimens were stained with an antibody that could recognize activated NF-kappaB and p65 to determine whether they were positive or negative for NF-kappaB activation. The clinical courses of the 28 patients were then correlated with the results of the NF-kappaB staining. The 10 men and 18 women had a mean age of 57.3 years (range, 25-87 years). By follicular lymphoma grade, 10 patients had grade 1, 16 had grade 2, and 2 had grade 3a. Ten patients died due to lymphoma. NF-kappaB was positive in 6 of the 28 cases. Analysis of the positive and negative staining groups while taking into account the clinical course, sex, age, grade of follicular lymphoma, prognostic index, CD10, CD23, Bcl-2, karyotype t(14;18), and survival showed that no significant differences. Six of the 28 lymph nodes (21.4%) exhibited consistent NF-kappaB activity. Three of the eleven cases that transformed to aggressive lymphoma were positive for activated NF-kappaB. Further research to clarify the significance of constitutive NF-kappaB activity in follicular lymphoma is therefore warranted.

CD3- and CD4-positive plasmablastic lymphoma: a literature review of Japanese plasmablastic lymphoma cases.

Plasmablastic lymphoma (PBL) is a very rare and recently-described subtype of diffuse large B-cell lymphoma. A maxillary tumor in an 84-year-old HIV-negative Japanese-man was referred. The biopsied specimen showed a diffuse proliferation of mature plasma cells, expressing CD3 (+), CD4 (+), CD20 (-), CD138 (+) and EBER (+) by immunohistochemistry. He was diagnosed as a plasmablastic lymphoma; radiation therapy (RT) was started, but the response to the RT was only a partial response. To our knowledge, this is the first report of a patient with PBL expressing CD3 and CD4.

CD20-positive T-cell large granular lymphocyte leukemia: case report and review of the literature.

CD20-positive T-cell malignancy is a rare disease. We report a case of CD20-positive T-cell large granular lymphocyte leukemia (T-LGLL). The leukemic cells were positive for CD20 and T cell markers, such as CD3, CD4, CD5, CD8 and CD57. A monoclonal rearrangement of the T-cell receptor (TCR) beta chain gene was detected. Twenty-three cases of well-documented CD20-positive T-cell malignancies were reviewed. Most cases were mature T-cell malignancies, especially exhibiting a cytotoxic T-cell phenotype, despite a diversity of the pathological diagnoses. Additional cases must be evaluated to clarify the implications of CD20 expression on T-cell malignancies and to elucidate whether such cases constitute a distinct biologic and clinical disease entity. The accumulation of cases will help to facilitate provision of a proper treatment for CD20-positive T-cell malignancies in the future.

Remission of lymphoma after withdrawal of methotrexate in rheumatoid arthritis: relationship with type of latent Epstein-Barr virus infection.

Rheumatoid arthritis (RA) is associated with an increased risk of developing lymphoma. Although the pathogenesis is still unclear, the increased risk appears to be related to the high inflammatory activity of RA, immunosuppressive agents, or Epstein-Barr virus (EBV) infection. We investigated the relationship between EBV latent infection and methotrexate (MTX)-associated lymphoma in RA patients. Nine patients were diagnosed with non-Hodgkin's lymphoma (NHL) during MTX treatment for RA in a multicenter study. The pathologic findings were consistent with diffuse large B-cell lymphoma in 8 patients and peripheral T-cell lymphoma, unspecified in 1. EBV infection was detected in 3 patients by in situ hybridization. Among all 9 patients who were initially treated by MTX withdrawal alone, 2 obtained spontaneous complete response (CR), 1 had partial response, 2 had stable disease (SD), and 4 had progressive disease. Both patients who had a CR and 1 who had SD were positive for EBV. Further examination of the latent EBV infection patterns revealed that 2 patients who obtained a CR had latency Type III, and the other with SD had latency Type II. These results demonstrate that immunodeficiency caused by MTX treatment is associated with the development of EBV-related NHL in RA patients. In patients who were treated by MTX for RA and developed NHL, remission can be observed following MTX withdrawal especially in NHL with latency Type III EBV infection. The analysis of EBV infection, including the latency types, is useful to decide the optimum therapeutic strategy.