[High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma].

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.

[B precursor lymphoblastic leukemia/lymphoma manifested at onset as hemophagocytic syndrome].

A 20 year-old male patient was admitted to our department for the treatment of recurrence of fever and pancytopenia developed despite of temporal remission of hemophagocytosis syndrome that had been treated with large doses of methylprednisolone in our hospital. Superficial lymph nodes were not palpable. CT scan and echography revealed neither findings of splenohepatomegalia or enlargement of intraabdominal lymph nodes. Bone marrow aspiration showed an increase of histiocytes, the cells phagocytizing erythrocytes and platelets, and a negative test for peroxidase stain. Analysis of surface antigens showed that 11.3% of cells were blast cells positive for CD10, CD19, CD20, CD34 and TdT. Bone marrow biopsy revealed a localized increase in tumor cells positive for L26, CD10 and negative for UCHL-1. Because of the absence of detectable tumor masses and the difficulty in differentiating between malignant lymphoma and lymphatic leukemia, we diagnosed the condition as B precursor lymphoblastic leukemia/lymphoma. If diagnosed with malignant lymphoma preceded by hemophagocytic syndrome(LAHS), he might have a rare type of LAHS-associated malignant lymphoma since histological examination did not reveal diffuse large cell lymphoma, a condition found in most patients with LAHS-associated malignant lymphoma. Whereas if diagnosed as ALL, he was the first adult patient with ALL with HPS at onset as far as we know. In any of these possibilities, the case was considered rare.

[Flow cytometric analysis for the activation of peripheral immunoregulatory cells from patients with bronchial asthma].

By use of flow cytometry, we have investigated intracellular activated eosinophil cationic protein (ECP) in eosinophils and mitogen-induced cytokine production of T cells in peripheral blood from children with acute severe asthma. In addition, we measured ECP releasability (serum ECP/lysate ECP) as a maker of activated eosinophils. The monoclonal antibody EG2 (anti-activated ECP/EPX antibody) was used for measuring the amount of intracellular activated ECP. ECP releasability and mean fluorescence intensity (MFI) values of EG2-positive eosinophils increased at the time of asthmatic attack and reduced after treatment with improvement in peak expiratory flow. Furthermore, the frequency of T cells which produced IL-4, IL-5 and IFN-gamma stimulated with phorbol myristate acetate and ionomycin increased and reduced in parallel with MFI of EG2-positive cells. These observations suggest that flow cytometric analysis for intracellular ECP and mitogen-induced cytokine production reflects the activation of T cells in bronchial mucosa, and is useful for monitoring airway inflammation in bronchial asthma.

[Therapeutic effects of cefclidin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

One hundred thirty-eight patients with severe infections associated with hematopoietic disorders were treated with cefclidin (CFCL), and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Of the 126 patients in whom the efficacies were evaluable, 22 (17.5%) responded markedly well and 48 (38.1%) moderately, and the overall efficacy rate was 55.6%. 2. Efficacy rates for different infections were: 20.0% in septicemia, 61.2% in suspected septicemia, 46.7% in respiratory tract infection and 25.0% in others. 3. Significantly different efficacy ratings were observed between a group of patients with neutrophil counts of less than 100/mm3 and that with neutrophil counts of higher than 501/mm3. 4. Out of 138 patients in whom the safety was evaluable, side effects were observed in 5 patients (3.6%) and abnormal laboratory test values in 9 (6.5%). None was serious, however.

[Clinical evaluation of panipenem/betamipron in severe infections complicating hematological disorders].

Forty-three patients with severe infections which were complicating hematological disorders were treated with panipenem/betamipron, and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 40 patients in whom efficacies are evaluable, the clinical responses were excellent in 17 patients, good in 4, fair in 7 and poor in 12, and the total clinical efficacy rate was 52.5%. 2. The efficacy rate in 7 patients who had failed to respond to prior treatment with other antibiotics was 57.1%. Thus, no significant difference was observed in efficacy rates between the patients who had failed to respond to prior treatment with other antibiotics and the patients who received no preceding antibiotics therapy. 3. Out of the 43 patients in whom the safety was evaluable, no side effects nor abnormal laboratory findings were found.

Effects of ubenimex, a biological response modifier, on myelodysplastic syndrome and chronic leukemia.

Twenty cases of myelodysplastic syndrome (MDS) were treated with ubenimex. Seventeen cases were treated with the drug over 90 d. Among these, 10 showed improvement of anemia, 12 an increase in platelet count which had decreased before treatment and 10 an increase in neutrophil count; however, 14 showed an increase in blast percentage in bone marrow aspirate. CD4/CD8 ratio was increased in 4 cases and shifted to a normal from an abnormal range in 6 cases. When the MDS cases were observed in refractory anemia (RA) and refractory anemia with excess blasts (RAEB), great improvement was seen, but in RAEB increase in blast percentage was also observed. CD4 increased mostly in RA and CD8 increased in RAEB. Ten cases of chronic myelocytic leukemia (CML) were first treated with ubenimex and cytostatics, then with ubenimex only. Six cases attained partial remission within 3 months, but one case showed a marked increase in white cell count and blast count and in another case a progression of splenomegaly associated with increase in white cell count. From these findings we conclude that ubenimex could be utilized in MDS or CML if the patient was at risk for strong chemotherapy.

[Virus-associated hemophagocytic syndrome due to EB virus].

A 30-year-old man was admitted to our hospital because of fever and cervical lymphadenopathy. Hematological examination revealed leukocytosis with atypical lymphocytes in peripheral blood. Mature histiocytes with erythrophagia were detected in the bone marrow. GOT and GPT were elevated. Anti-EB virus antibody titer was high. The titers of VCAIgM and VCAIgG on admission were 1:320 and 1:160, respectively, and those at convalescence stage were 1: less than 10 and 1:640. The diagnosis of virus associated hemophagocytic syndrome (VAHS) due to EB virus was made. Immunosuppressive and cytotoxic therapy are thought to be contraindicated in the treatment of VAHS. In this case only a febrifuge was administrated and the condition of the patient was improved.

[Therapeutic effects of imipenem/cilastatin sodium against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

One hundred ninety-eight patients with severe infections associated with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and safety of the drug were evaluated. The results obtained are summarized below. 1. Out of 182 patients in whom efficacies are evaluable, responses were excellent in 50 patients, good in 52, fair in 21 and poor in 59, and the efficacy rating was 56.0%. 2. The efficacy rating in 87 patients who had failed to respond to prior treatment with other antibiotics was 58.6%. 3. There were significant differences in efficacy ratings when patients were grouped according to differences the number of neutrophils after treatment, less than 100, 101 approximately 500 and over 501/mm3. 4. The eradication rate in 38 patients from whom causative organisms were isolated was 75.8%. 5. Out of 197 patients in whom the safety was evaluable, side effects were observed in 19 patients (9.6%) and abnormal laboratory test values in 15 (7.6%).

[Acute myeloid leukemia after the treatment of Hodgkin's disease].

A 55-year-old woman developed a secondary leukemia following 1-year treatment of Hodgkin's disease. She was admitted to our hospital because of the celiac lymphadenopathy. Open laparotomy was performed. Biopsy specimens of the lymph node demonstrated Reed Sternberg cells with mature lymphocytes. She was diagnosed as having Hodgkin's disease (lymphocyte predominant type). She was treated by the combination chemotherapy consisting of mitoxantrone, cyclophosphamide, vincristine and prednisolone for Hodgkin's disease in November 1986. Hodgkin's disease achieved complete remission and she was regularly followed. No abnormal findings were observed in the peripheral blood and bone marrow. But thrombocytopenia and the blastoid cells appeared in the peripheral blood in February 1988. The bone marrow specimen was hypercellular and occupied by 90% of blastoid cells that were positive for peroxidase staining. She was diagnosed as having AML from the bone marrow aspiration and biopsy specimens. She did not respond to several chemotherapy regimens and now she is treated by low dose Ara C.

[Leukemic Burkitt's lymphoma with an initial symptom of ocular motor disturbance].

A 58-year-old male was admitted to Osaka City University Hospital because of diplopia in May, 1987. Hematological examinations revealed abnormal blastoid cells in his peripheral blood and bone marrow. We found many mitochondria and polysomes in the cytoplasm of the blastoid cells by the electron microscopy. Moreover, left axillary lymph node biopsy specimen disclosed the typical "starry sky" pattern. The blastoid cells in the bone marrow had chromosomal abnormality; 47XY, 8q-, 14q+, 22q-, +mar. Therefore, the diagnosis of Burkitt's lymphoma (leukemic change) was performed. He was treated with chemotherapy, but the blastoid cells resisted many anticancer agents and he died in September 30. On admission left ocular motor disturbance was revealed. Generally, it was reported that meningitis with CNS involvement of lymphoma is accompanied by cranial nerves palsy. However in this case lymphoma cells was not found in the cerebrospinal fluid. The cause of ocular motor disturbance was the adhesion to the medial rectus muscle and compression to the ocular motor nerves of the lymphoma mass.

One-day intravenous therapy with high-dose gamma-globulin for idiopathic thrombocytopenic purpura.

The effects of one-day intravenous therapy with gamma-globulin in a 25-year-old man with idiopathic thrombocytopenic purpura are reported. The patient showed resistance to prednisolone and had bleeding tendency. The thrombocytopenia improved after the intravenous administration of gamma-globulin at a dose of 1 g/kg. Splenectomy was carried out. The results suggested that the usual dose of gamma-globulin is not always necessary. The half-dose increased the platelet count.

Effects of forskolin and cilostazol on clot retraction.

We examined the effects of two inhibitors of aggregation of human platelets the, Forskolin and Cilostazol on clot retraction. Both substances suppressed clot retraction in a dose-dependent way. Both suppress platelet aggregation because of an increase in intercellular cyclic AMP, but there was no close correlations were shown between suppression rate for clot retraction and cyclic-AMP content in platelets in the clot in each substance. Furthermore, although it has been considered that actomyosin in platelets is a major contractile source for clot retraction and that failure of actin polymerization results suppression of clot retraction. As it was difficult to obtain active actin from platelets of the reagents on the polymerization. Cilostazol accelerated actin polymerization, whereas Forskolin did not. From these findings, it was considered that the effects of both substances on clot retraction could not be interpreted directly just by the increasing effect for intracellular cyclic-AMP. Clot retraction is consider to be a in vitro model of hemostasis and its contractile force is supplied from platelets (1,2,3). Experiments used prostaglandin E-1 revealed that elevation of cyclic-AMP (c-AMP) would regulate the clot retraction, and experiments used cytochalasin B demonstrated that actomyosin is responsible to the retraction (4,5). Many date demonstrate that elevation of c-AMP level suppresses platelet aggregation (6,7). c-AMP, therefore, should play a key role on platelet activation. Forskolin and Cilostazol are newly-developed reagents as a suppress for platelet functions. Pharmacological action of these substances have been interpreted to process increase effect for intracellular c-AMP of platelets(8,9). If so, both substances should show some effect on clot retraction. Under this assumption, we examined the effects.