Hiroe Kanamori

Reactivation of hepatitis B virus with rituximab.

Rituximab has become a useful drug for the treatment of non-Hodgkin’s lymphoma (NHL) and such autoimmune diseases as idiopathic thrombocytopenic purpura and rheumatoid arthritis. When combined with cytotoxic agents, rituximab showed synergistic effects for the treatment of NHL. In such treatment, hepatitis B virus (HBV) reactivation is a crucial complication when patients are treated with immunosuppressive or chemotherapeutic agents. Despite its treatment efficacy, several studies have pointed out unusual viral infections after its administration that resulted in fatal hepatitis due to HBV reactivation. In the cases at the authors’ institute, the authors analysed the kinetics of HBV antibodies, HBV-reactivation timing, and the prophylactic efficacy of lamivudine. The authors reviewed their cases and the previous literature to clarify the characteristics of HBV-reactivated patients who were administered rituximab.

Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin's lymphoma

We used regimens containing rituximab in the treatment of five hepatitis B virus surface antibody (HBsAb)-positive patients with non-Hodgkins lymphoma (NHL). Serum levels of HBsAb were obtained and analyzed in four of these patients. Two patients were HBs antigen (HBsAg) positive. One of these HBsAg-positive patients was treated with lamivudine because the patient developed fulminant hepatitis from hepatitis B virus (HBV) infection prior to chemotherapy. However, none of the other patients were administered lamivudine. An HBsAg-positive patient who did not receive lamivudine treatment later developed fulminant hepatitis. Another HBsAg-positive patient receiving lamivudine prophylaxis did not develop severe hepatitis arising from HBV. In the three patients not receiving lamivudine treatment, serum HBsAb titers decreased soon after the administration of rituximab. These results suggest that rituximab reduced the antibody titer for HBV, thus inducing an immunological environment leading to easy reactivation of HBV. Lamivudine prophylaxis was effective, at least when rituximab was given to an HBsAg-positive patient with non-Hodgkins lymphoma.

Hepatitis B Virus Reactivation in a Case of Non-Hodgkin's Lymphoma Treated with Chemotherapy and Rituximab: Necessity of Prophylaxis for Hepatitis B Virus Reactivation in Rituximab Therapy

A patient with Non-Hodgkins lymphoma is reported, in which reactivation of the hepatitis B virus was achieved from treatment with rituximab. The patients HBs antigens were positive on admission, and she tested positive for HBs, HBe, and HBc antibodies, and negative for the HBe antigens. She was treated with a regimen of three courses of rituximab-containing anti-cancer drugs and one course of combined anti-cancer drugs. Throughout these chemotherapy courses, prednisolone was not given. After the fourth course of chemotherapy with the third rituximab she developed hepatic dysfunction, and the serum titers of HBs and HBc antibodies suddenly decreased. After administration of lamivudine, however, she gradually recovered from liver failure.

Randomized study of Helicobacter pylori eradication therapy and proton pump inhibitor monotherapy for idiopathic thrombocytopenic purpura

Helicobacter pylori (HP) eradication therapy is a useful treatment for idiopathic thrombocytopenic purpura (ITP). Some investigators have also reported the effects of proton pump inhibitor (PPI) monotherapy on ITP. We performed a randomized study of HP eradication therapy and PPI monotherapy on ITP. Four of nine patients achieved complete remission (CR), two of nine achieved partial remission (PR) in HP eradication therapy, three of eight achieved CR, and two of eight achieved PR in PPI monotherapy. No significant differences were observed in the CR + PR of these patients between HP eradication therapy and PPI monotherapy. As for cost comparisons, HP eradication therapy is cheaper than PPI monotherapy, but it is less effective.

Delayed reduction in left ventricular function following treatment of non-Hodgkin's lymphoma with chemotherapy and rituximab, unrelated to acute infusion reaction.

We report 3 cases of reduced cardiac function with complications in non-Hodgkin’s lymphoma patients who were treated with rituximab. Patients experienced reduced cardiac functions after the administration of rituximab; there was no evidence of any preceding infusion reactions. Reticulin fiber was observed diffusely in cardiac muscles. Transforming growth factor-β levels were elevated after the administration of rituximab. We believe that continuous elevation of transforming growth factor-β may promote the growth of reticulin fiber in cardiac muscles. Reduction in cardiac functions is a severe complication that must be considered when rituximab is administered.

Aleukemic leukemia cutis in a patient with Philadelphia chromosome-positive biphenotypic leukemia

Aleukemic leukemia cutis is a rare condition characterized by the invasion of leukemic blasts into the skin before their appearance in the peripheral blood. Leukemia cutis usually occurs in patients with myeloid leukemia, especially the myelomonocytic and monocytic types of acute myeloblastic leukemia. We describe the case of a 62-year-old woman with aleukemic leukemia cutis who developed Philadelphia-positive acute leukemia 1 month after skin involvement. Leukemic cells expressed both myeloid and B-cell lineage surface markers, and monoclonal rearrangement of the immunoglobulin heavy chain was detected by Southern blot analysis. This report is the first of a case of aleukemic leukemia cutis preceding Philadelphia-positive biphenotypic leukemia.

Fungemia due to Trichosporon dermatis in a patient with refractory Burkitt's leukemia

TO THE EDITOR: This is a rare case report of fungemia caused by Trichosporon dermatis in a patient with refractory Burkitts leukemia who was administered prophylactic voriconazole.

Effectiveness of propagermanium treatment in multiple myeloma patients

Interferon (IFN) is one of several drugs effective in treating multiple myeloma (MM), and propagermanium is an IFN inducer. We report on 10 MM patients who were treated with propagermanium at doses from 10 to 40 mg. Two patients achieved complete remission (CR), two patients achieved partial remission (PR), and the condition of four patients was stable (stable disease, SD). After discontinuation of propagermanium, the status of MM progressed in two patients who were in SD and in two patients who had achieved PR. The administration of propagermanium was restarted in one patient resulting in a decrease in her paraprotein.

Pseudomembranous tracheobronchial aspergillosis.

A 49-year-old man received systemic combination chemotherapy for treatment of recurrent angioimmunoblastic T-cell lymphoma. He developed autoimmune haemolytic anaemia that was treated with corticosteroids, which was complicated by secondary diabetes mellitus. Levofloxacin and fluconazole were given orally for prophylaxis of opportunistic bacterial and fungal infections. During myelosuppression after chemotherapy, sore throat and hoarseness appeared and worsened. Repeated cultures of oropharyngeal smears and sputum showed no signs of bacterial or fungal infection. Serological markers of fungal infection, including Candida antigen, Aspergillus antigen and b-D glucan, were negative. A chest radiograph did not show an abnormal shadow. Computed tomography showed several small nodules of 2–4 mm in diameter in both upper lung fields. His sore throat progressed to anterior chest pain and he completely lost his voice. Fibreoptic bronchoscopy examination showed multiple pseudomembranous cream-coloured plaques extending from the vocal cords into both main bronchi (Fig. 1a). Papanicolaou staining of brushings from the plaques showed numerous filamentous septate hyphae (Fig. 1b), and Aspergillus fumigatus grew in culture. These findings are characteristic of tracheobronchial aspergillosis. Tracheobronchial involvement is an uncommon form of invasive pulmonary aspergillosis and is found mainly in immunocompromised individuals, such as patients with haematological malignancy, patients with prolonged granulocytopenia due to cytotoxic therapy, organ-transplant recipients and patients with HIV/AIDS. The pseudomembranous form is the most severe condition and is usually fatal despite treatment with antifungal agents. Our patient showed significant improvement after 1 month of treatment with inhaled amphotericin B and oral voriconazole, with resolution of the tracheal pseudomembranes (Fig. 1c).

Successful treatment of lymphoma with fludarabine combined with rituximab after immune thrombocytopenia induced by fludarabine

A 47-year-old man was diagnosed with non-Hodgkin’s lymphoma (NHL) follicular B-cell type (stage IVB). Although partial remission was observed after the administration of several combination chemotherapeutic agents, no more improvement was observed. After we finished the FND (fludarabine, mitoxantrone, dexamethasone) regimen, the patient’s status improved. After the administration of the FND regimen, thrombocytopenia developed, and the platelet count did not recover to previous levels. After rituximab was administered for the treatment of thrombocytopenia, the platelet count recovered. Then we combined fludarabine and rituximab for the treatment of NHL. Although fludarabine was administered, the platelet count did not decrease when combined with rituximab. In the discussion, we analyze the characteristics and the treatment outcome of the thrombocytopenia induced by fludarabine reviewed in the literature.