Shinji Obara

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.

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.

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.

Myelofibrosis after essential thrombocythemia complicated by alveolar proteinosis.

Hematological diseases are often accompanied by respiratory disorders. Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by excessive accumulation of surfactant in the alveolar space. We describe a case of PAP complicated by myelofibrosis following essential thrombocythemia. The patient developed high fever, respiratory failure, and leuko-erythroblastosis during the progressive course of PAP. These symptoms were alleviated by prednisolone. The level of serum IL-6 was elevated when PAP was progressing rapidly. This may explain why the symptoms were alleviated by the steroids.

Leukoencephalopathy with cerebral hemorrhage following acute pancreatitis due to tacrolimus in a case of allogeneic peripheral blood stem cell transplantation.

disease variant of Richter’s syndrome in chronic lymphocytic leukaemia patients previously treated with fludarabine. British Journal of Haematology 2005;129:199 – 205. 10. Sklar J, Cleary ML, Thielemans K, Gralow J, Warnke R, Levy R. Biclonal B-cell lymphoma. New England Journal of Medicine 1984;311:20 – 27. 11. Siegelman MH, Cleary ML, Warnke R, Sklar J. Frequent biclonality and Ig gene alterations among B cell lymphomas that show multiple histologic forms. Journal of Experimental Medicine 1985;161:850 – 863. 12. Novak PM, Mattson JC, Crisan D, Chen J, Poulik MD, Decker D. Separate clones in concomitant multiple myeloma and a second B-cell neoplasm demonstrated by molecular and immunophenotypic analysis. European Journal of Haematology 1995;54:254 – 261. 13. Gonzalez-Campos J, Rios-Herranz E, De Blas-Orlando JM, Martin-Noya A, Parody-Ruiz-Berdejo R, RodriguezFernandez JM. Chronic lymphocytic leukemia with two cellular populations: a biphenotypic or biclonal disease. Annals of Hematology 1997;74:243 – 246. 14. Fend F, Quintanilla-Martinez L, Kumar S, Beaty MW, Blum L, Sorbara L, et al. Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection. American Journal of Pathology 1999;154:1857 – 1866. 15. Hsi ED, Hoeltge G, Tubbs RR. Biclonal chronic lymphocytic leukemia. American Journal of Clinical Pathology 2000;113: 798 – 804. 16. Gine E, Bosch F, Villamor N, Rozman M, Colomer D, LopezGuillermo A, et al. Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association? Leukemia 2002;16: 1454 – 1459. 17. Shimizu S, Tamagawa Y, Kojima H, Mori N, Nagata M, Noguchi M, Nagasawa T. Simultaneous development of lymphoplasmacytic lymphoma and diffuse large B-cell lymphoma—analyses of the clonal relatedness by sequencing CDR3 in immunoglobulin heavy chain genes. European Journal of Haematology 2003;70:119 – 124. 18. Macdonald D, Reiter A, Cross NC. The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1. Acta Haematologica 2002; 107:101 – 107. 19. Gregersen H, Ibsen J, Mellemkjoer L, Dahlerup J, Olsen J, Sorensen H. Mortality and causes of death in patients with monoclonal gammopathy of undetermined significance. British Journal of Haematology 2001;112:353 – 357. 20. Pilarski LM, Andrews EJ, Mant MJ, Ruether BA. Humoral immune deficiency in multiple myeloma patients due to compromised B-cell function. Journal of Clinical Immunology 1986;6:491 – 501.