Ulcerative colitis after autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A 54-year-old woman with peripheral T cell lymphoma in second complete remission (CR) received an autologous peripheral blood stem cell transplant (PBSCT). Antibiotic-resistant bloody diarrhea, and fever developed 110 days after transplant. Blood and stool cultures were negative. Skin rash was not observed. Barium enema and colonoscopy showed typical features of pancolonic-type ulcerative colitis (UC). Endoscopic biopsies confirmed the diagnosis of UC. Mesalazine and immunosuppressive therapy improved symptoms dramatically. We detected serum antibodies against synthetic tropomyosin (TM) peptide when UC was diagnosed. We postulate that autoimmunity including autoreactive anti-TM antibodies may be involved in the pathogenesis of UC after autologous PBSCT in this patient.

[Diagnosis and prognosis of reactive lymphoreticular hyperplasia (RLH) or mucosa-associated lymphoid tissue (MALT) lymphoma].

We studied the diagnostic significance of immunohistolochemical staining and immunoglobuline gene rearrangement of jumbo-biopsy specimen from 14 patients with stomach lesions which were difficult to distingwish between reactive lymphoreticular hyperplasia (RLH) and mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). We also investigated Helicobacter pylori (HP) infection in the patients and followed their clinical courses from a mean observation period of 3 years and 4 months following initial diagnosis. As a result, 7 of the 14 cases were diagnosed as having MALT lymphoma. All of them were resected, and then the diagnosis was confirmed. Metastasis was found in 2 cases. The other 7 cases were diagnosed as RLH. A favorable prognosis during follow up without any treatment supported the belief that they were non-malignant lesions. HP infections were observed on 83% of the RLH cases and 57% of MALT lymphoma cases. In one of the case of RLH, the lesion disappeared after eradication of HP.

[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.

[Diagnostic value of serum soluble interleukin-2 receptor levels in interstitial pneumonia of the patients with hematological disorders].

Serum levels of soluble interleukin-2 receptor (SIL-2R) and C-reactive protein (CRP) were measured in 12 patients with interstitial pneumonia (IP) and 10 patients with bacterial pneumonia (BP) of hematological malignancies. Mean SIL-2R levels (U/ml) were 394 +/- 140 in normal controls, 755 +/- 320 in BP, and 2328 +/- 943 in IP. A significantly higher level was found in IP than BP (p < 0.05). Moreover, the SIL-2R/CRP ratio which was over 260 in all cases of IP completely distinguished IP from BP. Levels of SIL-2R rose before the onset of IP and were closely associated with clinical course in most cases. From these results, measurement of serum SIL-2R may be useful for the diagnosis and monitoring of the clinical course of IP complicated with hematological diseases.

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.

Immunoblastic lymphadenopathy-like T-cell lymphoma displaying rearrangement of both IgH and TCR beta genes after 4-year follow-up of idiopathic eosinophilia.

Immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma (IBL-T) occurred in a 60-year-old female after a 4-year follow-up of idiopathic eosinophilia and upper pharyngeal inflammatory tumor with infiltration of mature eosinophils. Gene analysis of tumor cells revealed rearrangement of both IgH and TCR beta genes. The patient died of lymphoma seven months after the onset of the illness, in spite of chemotherapy against lymphoma. The relationship between eosinophilia and the pathogenesis of IBL-T, as well as the significance of the rearrangement of both IgH and TCR beta genes are discussed.

[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.

Bone marrow transplantation for hematological diseases in Hokkaido--June 1985 to December 1991.

Bone marrow transplantation (BMT) was started in Hokkaido in 1985. In the present report we have reviewed the clinical outcome of patients treated with BMT for hematological diseases in Hokkaido. Fifty-eight allogeneic and 19 autologous transplants were registered by December 1991. The underlying diseases consisted of 47 leukemias, 14 lymphomas, 10 aplastic anemias and six myelodysplastic syndromes. Among the allogeneic BMT cases, 55 were human leucocyte antigen (HLA) identical and three were mismatched. Among the autologous BMT patients, two received their marrow purged with 4-hydroperoxycyclophosphamide and five, with monoclonal antibodies and complements. The conditioning regimens used for malignancies were chiefly cyclophosphamide (CY) plus total body irradiation, or busulfan plus CY. In many cases, cytokines were used for rapid recovery of decreased leukocytes. Engraftment was observed in 50 out of 52 evaluated allogeneic and 18 out of 19 autologous transplants. Ten allogeneic patients suffered from severe acute graft-versus-host diseases (GVHD), and extensive chronic GVHD appeared in 16 patients. Relapses were observed in four cases of allogeneic BMT and six of autologous BMT. The major complications were interstitial pneumonitis (IP) and severe infections. Long-term survival rates were almost 60% in both allogeneic and autologous transplants. Mild acute GVHD and limited chronic GVHD increased the survival rates. The results indicated that substantial problems such as GVHD, IP and relapses must be controlled in the near future for an improved outcome to be made possible.

[Successful treatment of prolonged anemia after major ABO incompatible bone marrow transplantation for a case of myelodysplastic syndrome with recombinant erythropoietin].

A delay in red cell recovery after ABO-incompatible bone marrow transplantation (BMT) is often observed. The authors experienced a case of prolonged anemia after a major ABO incompatible BMT for myelodysplastic syndrome which was successfully treated with recombinant human erythropoietin (Epo). Effects of Epo were confirmed by the recurrence of anemia after withdrawal of Epo as well as the rapid reincrease in reticulocytes on readministration. The patient received a dose of Epo which was similar to the amount used for renal anemia, however serum concentration of Epo after administration exceeded endogenous Epo levels. Epo may have a beneficial role in the treatment of prolonged anemia after BMT.

[Combination chemotherapy of UFT with adriamycin (ADM) and cisplatin (CDDP) for advanced gastrointestinal cancer].

Thirty four patients with advanced gastric cancer (GC), colon cancer (CC) biliary tract cancer (BC) and pancreatic cancer (PC) were treated with a combined chemotherapy of UFT with ADM (UFT-A), or UFT with ADM and CDDP (UFT-AC). The UFT-A regimen consisted of UFT, 600 mg/body daily. As for ADM, 10 mg/body was given intravenously from day 1-4 and repeated every two weeks. The UFT-AC regimen consisted of UFT 400-600 mg/body daily. As for ADM, 7.5 mg/m2 was given from day 7-9 and CDDP 50 mg/m2 on day 7, repeated every 3-4 weeks. Partial responses (PR) were seen in 7 cases (36.8%) (5 cases of GC, 1 case of CC and 1 case of BC) out of 19 evaluable patients (8 cases of GC, 4 cases of CC, 4 cases of BC and 3 case of PC) treated with UFT-A. Complete response in a case of CC and PR in 6 cases (47.7%) (3 cases of GC and 3 cases of BC) were observed out of 15 evaluable patients (7 cases of GC, 2 cases of CC, 4 cases of BC and 2 cases of PC) treated with UFT-AC. There was no significant difference of survival curve between the two regimens, however, the median survival of responders for both regimens is longer than non-responders with statistical significance. As for side effects, UGI symptoms were recognized in 37% of UFT-A group and in 73% of UFT-AC group. A leukopenia count of less than 2,000/mm3 appeared in 11% of UFT-A group and in 20% of UFT-AC group. Considering these results, UFT-A and UFT-AC therapy appears to be useful in cases of advanced gastrointestinal cancer, especially gastric cancer.