Takahito Kawamura

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.

Relationship between Preexisting Anti-Varicella-Zoster Virus (VZV) Antibody and Clinical VZV Reactivation in Hematopoietic Stem Cell Transplantation Recipients

ABSTRACT Reactivation of latent varicella-zoster virus (VZV), presenting as localized zoster or as disseminated infection, is a common and potentially serious complication in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively studied anti-VZV immunoglobulin G titers by the immune adherence hemagglutination method after HSCT and also studied VZV DNA by real-time PCR during clinical VZV reactivation using cryopreserved serum samples. No significant difference was found between anti-VZV titers in 13 patients with VZV infection (localized zoster in 11 patients and disseminated zoster in 2 patients) and in 13 subjects without VZV infection at each time point after HSCT. Preexisting anti-VZV titers of disseminated zoster cases tended to be lower than those of localized zoster cases (P = 0.10). Serum VZV DNA copy numbers at the onset of disseminated zoster cases tended to be higher than those of localized zoster cases (P = 0.09). A strong inverse correlation was found between preexisting anti-VZV titer and serum VZV DNA at onset (r = −0.90, P = 0.006). In HSCT recipients, preexisting antibody does not prevent the development of VZV reactivation but may contribute to decreased viral load at onset, resulting in a mild clinical course.

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.

Successful Reduced-Intensity Stem Cell Transplantation With Cord Blood for a Poor-Prognosis Adult with Refractory Chronic Active Epstein-Barr Virus Infection

A 56-year-old woman with a poor-prognosis chronic active Epstein-Barr virus (CAEBV) infection underwent reduced-intensity stem cell transplantation (RIST) using cryopreserved cord blood (CB). Administration of EBV-seronegative CB cells following a reduced-intensity conditioning regimen was effective and well tolerated. Complete remission with no symptoms, low titers of EBV-related antibodies, and an undetectable level of EBV DNA in peripheral blood mononuclear cells continued for 16 months after RIST This report is the first of successful RIST with CB for an adult with CAEBV infection. The results also show that a graft-versus-CAEBV effect can be achieved in an allogeneic hematopoietic stem cell transplantation setting.

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.

Graft-versus-tumor effect after reduced-intensity allogeneic hematopoietic stem cell transplantation in a patient with advanced colon cancer

A 27-year-old man with advanced colon cancer that was resistant to conventional chemoradiotherapies was treated with reduced-intensity allogeneic peripheral blood stem cell transplantation (PBSCT). After obtaining complete donor-type chimerism, there was an apparent graft-versus-tumor effect accompanied by severe hepatic graft-versus-host disease (GVHD) showing hyperbilirubinemia, resulting in a stable disease condition that lasted for 18 months, which had not been seen previously in his previous disease history. The antitumor effect observed in this patient was insufficient for the patient to achieve complete remission, because the disease was at an already widespread and treatment-resistant stage. He finally died of hepatic failure due to extensive liver GVHD 65 months after the diagnosis of the advanced colon cancer and 29 months after the allogeneic PBSCT. Prospective studies are necessary to achieve better clinical results in patients with advanced colon cancer.

Hyponatremia after administration of conditioning regimen in myelodysplastic syndrome with empty sella after glandula pituitaria surgery

Dear Editor, A 51-year-old woman who had developed myelodysplastic syndrome with an excess of blast [myelodysplastic syndrome (MDS), refractory anemia with excess blast (RAEB)] was admitted to our institution. She obtained complete remission after an administration of a low dosage of cytarabine. Then, she was administered busulfan (BU, 4 mg/kg for 2 days), fludarabine (FLU, 30 mg/m for 6 days), and total body irradiation (TBI, 2 Gy twice a day) as a conditioning regimen for unrelated stem cell transplantation (SCT) from a human leukocyte antigen (HLA) completely matched donor. Hyponatremia developed after the administration of BU, and the patient developed general fatigue. Her serum sodium level had fallen to 118 mEq/l (normal range from 135 to 147 mEq/l), plasma osmolarity was 240 mOsm/kg/H2O (normal range from 280 to 300 mOsm/kg/H2O), urine osmolarity was 502 mOsm/kg/l, and antidiuretic hormone (ADH) level was 2.3 pg/ml (normal range from 0.3 to 3.5 pg/ml) without edema. These facts suggested that an inappropriate secretion of ADH (SIADH) had developed after the conditioning regimen. After treatment with hypertonic saline infusion and minocycline hydrochloride (MINO), her hyponatremia gradually recovered. On the fourth day of the conditioning regimen, her serum sodium level recovered to 138 mEq/l. Magnetic resonance imaging (MRI) of the glandula pituitaria only showed neurohypophysis (lobus posterior) due to the previously performed Hardy’s operation for her pituitary adenoma. Adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and adrenal hormone were all within normal ranges without hormone therapy support before SCT. Inappropriate secretion of ADH (SIADH) is characterized by water retention, hyponatremia, and central nervous system symptoms. It is induced by several factors including central nervous disorders, endocrine diseases, paraneoplastic syndromes, and such anticancer agents as vincristine and cyclophosphamide [1–4]. BU and FLU have never been reported as causes of SIADH. Our patient did not have any viral infection or disease recurrence, and only the administration of the conditioning regimen was evident after the development of SIADH. Kobayashi et al. reported hyponatremic patients after stem cell transplantation. They showed that being younger than 4 years old was a risk factor for hyponatremia after SCT. They suspected the release to be causative for the development of SIADH, especially in association with acute graft-versus-host disease (GVDH) [5]. But our case was an adult who developed SIADH before SCT. BU is transported to cerebrospinal fluid [6]. FLU effectively treats the invasion of the sanctuary space by chronic lymphocytic leukemia [7, 8], showing that FLU might also pass to the cerebrospinal fluid. Therefore, BU as Ann Hematol (2007) 86:843–844 DOI 10.1007/s00277-007-0291-9