[Utility of daily oral administration of etoposide in 25 cases of refractory hematological malignancies].

We estimated the utility of daily oral administration of etoposide (ETOP) in 25 cases of refractory hematological malignancies who had been admitted to our hospital between February, 1988 and October, 1995. Patients were 9 cases of malignant lymphoma, 7 cases of adult T cell leukemia (ATL), 7 cases of acute leukemia, 1 case of primary macroglobulinemia, and 1 case of chronic lymphocytic leukemia (CLL). Eight cases were elderly patients over 65 years old, 7 cases were refractory to previous chemotherapies, and 13 cases were relapsed cases. ETOP was administered at 25 or 50 mg per day for at least more than 3 consecutive weeks, if the peripheral white blood cell count exceeded 1,000/microliter. Complete and partial responses were obtained in 64% of all cases, especially in 81% of malignant lymphoma and ATL. Probability of survival for 3 years of malignant lymphoma and ATL was 36.7%. As mild toxicities, 2 cases (8%) had nausea and vomiting, 2 cases (8%) had diarrhea, and 3 cases (12%) had stomatitis. Grade 3 leukocytopenia was observed in 16% of cases. Twelve out of 16 evaluable patients recovered in performance status (PS) after this therapy. Daily oral administration of ETOP might be an effective therapy for refractory hematological malignancies, especially for malignant lymphoma.

Pulmonary veno-occlusive disease accompanied by microangiopathic hemolytic anemia 1 year after a second bone marrow transplantation for acute lymphoblastic leukemia.

Although hepatic veno-occlusive disease (HVOD) is a common complication of allogenic bone marrow transplantation (BMT), pulmonary veno-occlusive disease (PVOD) is very rare. Only three cases have been described in the literature. We report the case of a 19-year-old woman who developed PVOD accompanied by microangiopathic hemolytic anemia (MAHA) and hemolytic uremic syndrome (HUS) 1 year after a second BMT for relapsed acute lymphoblastic leukemia (ALL). Autopsy examination revealed obstruction of the small pulmonary veins with edematous thickening of the intima. These findings are compatible with PVOD. Pulmonary GVHD and pulmonary aspergillosis were also observed. Various etiologic factors have been implicated in PVOD after BMT. We postulate that pulmonary GVHD and pulmonary infection including aspergillosis played an important role in the occurrence of both PVOD and HUS in our patient. Microangiopathic cytokines released in response to the GVHD and infection may damage the intima of microvessels that were previously injured by the two BMT. Despite appropriate therapy, the microangiopathic process was irreversible and the patient died. Thus, measures must be taken to prevent and treat PVOD after BMT.

Syndrome of the sea-blue histiocyte.

A 39-year-old male was admitted with fever, systemic lymph node swelling, liver dysfunction and mild splenomegaly. Liver biopsy specimen showed histiocytic aggregation in portal areas. These histiocytes were closely packed with granules, dyed sea-blue with May-Giemsa staining. Further microscopical examination of lymph nodes, gastro-intestinal tract and bone marrow also revealed the accumulation of sea-blue histiocytes. Activities of lipid metabolic enzymes were normal and hematopoietic diseases which are sometimes accompanied by secondary sea-blue histiocytosis were ruled out. We diagnosed this case as syndrome of the sea-blue histiocyte.

[Two cases of adult T-cell leukemia . lymphoma (ATL) with long-term remission by chronic daily administration of low-dose etoposide].

We tried long-term oral administration of low-dose etoposide (LDE) for seven patients with adult T-cell leukemia . lymphoma (ATL) at Asahikawa Red Cross Hospital in 1988. Two long-term survivors are presented. Case 1: A 53-year-old man was diagnosed as acute ATL in 1987. Because VEPA therapy was not effective, LDE (50 mg/day) therapy was started. Five months after entering CR, a lymphoma recurrence in the skin was observed. Retreatment with LDE and radiation therapy was effective, but he died of reprogression of ATL three years and seven months following initial diagnosis. Case 2: A 43-year-old woman was diagnosed as acute ATL in 1989. With LDE (50 mg/day) therapy for 40 days, she entered CR. The lymphoma recurred in the central nervous system (CNS) and skin in 1992. After radiation of CNS and LDE therapy, she showed CR again. She is alive now over five years and eight months after diagnosis.

[A case of chronic neutrophilic leukemia accompanied with severe bone marrow fibrosis which was effectively treated by hydroxyurea].

A 57-year-old man was admitted to hospital because of leukocytosis. He showed mild splenomegaly and, laboratory studies revealed elevated mature neutrophil count without morphological abnormality, mild anemia and elevated neutrophil alkaline phosphatase score. The serum granulocyte colony stimulating factor concentration was below 30 pg/ml. Bone marrow was a dry tap, and biopsy specimen revealed severe fibrosis. The peripheral blood karyotype was 46, XY with no rearrangement of bcr-abl. The patient was diagnosed as having chronic neutrophilic leukemia (CNL) with bone marrow fibrosis. He was successfully treated with hydroxyurea (HU) 1000 mg/day. The peripheral blood leukocyte was decreased to the normal level and, the bone marrow biopsy specimen changed mild fibrosis. During the follow up period of 11 months, the neutrophil count was well controlled without any side effect. This is a rare case of CNL accompanied with bone marrow fibrosis which was effectively treated by the administration of HU.

[Virus-associated hemophagocytic syndrome with interstitial pneumonia in adults and a review of literature in Japan].

A 21-year-old man was admitted with fever, jaundice, abdominal pain and general fatigue. Other clinical manifestations revealed liver dysfunction, hepatosplenomegaly, pancytopenia and disseminated intravascular coagulation. Anti-EB virus (EA-DR-IgG) was initially elevated on admission and was decreased after that, furthermore anti EBNA was elevated in the late period of his clinical course, which indicated primary infection or secondary alteration of EBV immunity. Bone marrow examination revealed hemophagocytosis by mature histiocytes. Therefore, he was diagnosed as Virus-associated hemophagocytic syndrome (VAHS). An arterial blood gas analysis on admission showed hypoxemia and findings of interstitial pneumonia (IP) were distinctly observed on chest CT scan. Steroid therapy was then initiated and the patient responded very well. The clinical findings and laboratory data including IP, were improved. The 20 adult cases of VAHS in Japan were clinically studied and a review of the complication of VAHS with IP was also made.

[NEO-MACOP-B chemotherapy for the treatment of advanced-stage aggressive non-Hodgkin's lymphoma].

We conducted a new chemotherapy, NEO-MAC OP-B (addition of etoposide and mitoxantrone to MACOP-B with half dose of methotrexate and half administration of doxorubicin), to reduce severe mucositis, which is a major toxic effect of MACOP-B, and to increase its effect with etoposide and mitoxantrone as new non-cross resistant drugs. Between Jan. 1989 and Mar. 1993, 12 patients with previously untreated advanced aggressive non-Hodgkin's lymphoma (NHL), 2 patients with adult T cell lymphoma, and 3 patients with relapsed NHL, were treated with NEO-MACOP-B. After termination of NEO-MACOP-B therapy, 83.3% of 12 patients with previously untreated NHL were in complete remission (CR). After median follow-up of 22 months, Kaplan-Meier estimates showed that overall survival of 12 previously untreated patients was 71.4%, and relapse-free survival of complete responder was 83.3%. Toxic effects on all 17 patients were moderate with a lower incidence of severe mucositis (only one patient with relatively severe stomatitis, WHO Grade 3). No treatment related deaths were observed. Thus, NEO-MACOP-B is an effective and safe treatment for advanced stage aggressive NHL.