[Hypogammaglobulinemia with a clinical course similar to that of drug-induced hypersensitivity syndrome].

A 30-year-old man consulted a local hospital because of upper abdominal pain and tarry stool and was admitted because of duodenal ulcer and hepatic dysfunction. On the fifth hospital day, he developed fever and erythema on the upper body. Liver biopsy demonstrated giant cell hepatitis, and interferon alpha was therefore administered. Liver function improved, though total bilirubin increased to 22.3 mg/dl. The eruption and fever improved in the 3rd hospital week, deteriorated again in the 5th hospital week, and then improved again in the 8th hospital week. Thereafter, he was transferred to our hospital for detailed examination of atypical lymphocytosis, lymphopenia, and hypogammaglobulinemia. Many lymph nodes measuring about 1 cm were detected by palpation. After admission to our hospital, lymphoadenopathy and fever improved. We measured the level of HHV-6 antibody since the clinical course was similar to that of drug-induced hypersensitivity syndrome (DIHS). HHV-6 IgG was x2,560, although it had been x160 at the previous hospital. The clinical course appeared similar to that of DIHS, but drugs known to cause DIHS had not been administered.

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.

HCV non-structural protein 3 and HCV RNA genome in non-Hodgkin lymphoma and transition of the serum HCV RNA level: a retrospective analysis in one institution.

There have been various reports on the association of hepatitis C virus (HCV) infection with B lymphocyte proliferative disorders, such as non-Hodgkin lymphoma (NHL). We experienced a case (Case 1) of anti-HCV antibody (HCV-Ab)-positive NHL in which HCV nonstructural protein 3 (NS3) expression was observed in lymphoma tissue at the time of recurrence and in which the serum HCV RNA level exhibited a transient increase prior to recurrence. We investigated the HCV RNA genome in lymphoma tissue in Case 1, and it could be detected at recurrence. We also investigated HCV NS3 protein expression in lymphoma tissue and changes in serum HCV RNA level during the clinical course in four other cases of HCV-Ab-positive NHL treated in our hospital. We examined lymphoma tissues for HCV NS3 protein expression in four of the five cases, but it was not identified except for in Case 1 at recurrence. In three cases with no recurrence, serum HCV RNA levels showed a tendency to decrease after completion of chemotherapy and became stable thereafter. Further studies are necessary to clarify the association between serum HCV RNA and the onset and exacerbation of NHL.

Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation.

Invasive fungal infection is one of the major causes of death in neutropenic patients undergoing allogeneic stem cell transplantation (SCT). Although prophylactic antifungal therapy with fluconazole (FLCZ) has become the standard care for these patients, there remains a need for more effective and cost-beneficial alternative drugs. We conducted a prospective study to evaluate the usefulness of the administration of micafungin (MCFG) as a prophylactic antifungal therapy for patients undergoing allogeneic SCT. The results were compared with previous data for patients who had received FLCZ. A total of 44 patients who underwent allogeneic SCT were enrolled in the study. Data from 29 patients who received allogeneic SCT using prophylactic FLCZ before this study were used as historical control data. Underlying diseases included acute leukemia (n = 16), non-Hodgkin's lymphoma (n = 11), myelodysplastic syndrome (n = 6), and others (n = 11) in the MCFG group and acute leukemia (n = 18), chronic myelogenous leukemia (n = 6), and others (n = 5) in the FLCZ group. The median durations of administration of MCFG and FLCZ were 36 and 34 days, respectively. Prophylactic success, defined as the absence of proven, probable, and possible invasive fungal infection (IFI) until the end of prophylactic therapy was achieved in 36 (87.8%) of the 41 evaluated patients in the MCFG group and in 65.5% of the patients in the FLCZ group (P = 0.038). No patients in the MCFG group showed proven or probable IFI, whereas proven or probable IFI was observed in three patients in the FLCZ group. Four patients in the MCFG group required dose escalation due to febrile neutropenia. Although one patient in the MCFG group required the discontinuation of MCFG due to allergic skin eruption (grade 2), none of the other patients in either group required dose reduction due to adverse effects. Although the study design was not a prospective randomized trial, our results indicate that the administration of MCFG at a daily dose of 100 mg is promising for prophylactic antifungal therapy in patients undergoing allogeneic SCT.

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.

Relationship between preexisting anti-varicella-zoster virus (VZV) antibody and clinical VZV reactivation in hematopoietic stem cell transplantation recipients.

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-beta levels were elevated after the administration of rituximab. We believe that continuous elevation of transforming growth factor-beta 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.

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.

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.

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-Hodgkin's lymphoma is reported, in which reactivation of the hepatitis B virus was achieved from treatment with rituximab. The patient's 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.

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.