[Clinical effects of combination therapy with cefozopran and tobramycin for severe infections in patients with hematologic diseases].

We studied clinical effect of a combination therapy with cefozopran (CZOP) and tobramycin (TOB) for infections in 80 patients with hematologic diseases in 15 institutes. Combined doses with CZOP 2 g and TOB 60-90 mg twice a day had been given intravenously. Of the 80 patients, 61 patients (42 with acute leukemia, 10 with malignant lymphoma, 3 with aplastic anemia, 2 with chronic myeloid leukemia, 2 with multiple myeloma, and 2 with myelodysplastic syndrome) were evaluable. Those consisted of 6 patients with septicemia, 49 with suspected septicemia, 3 with pneumonia, and 3 with other infections. Clinical efficacy by the treatment was excellent in 24, good in 17, fair in 9, and poor in 11 patients, and the overall efficacy rate including excellent and good was 67.2%. Microbiologically, 5 of the 6 patients with septicemia (1 coagulase negative Staphylococcus, 2 S. pneumoniae, 1 S. oralis, and 1 E. coli) were responded. The efficacy rate in patients with severe granulocytopenia showing 100/microliter or lesser neutrophil counts during the drug administration was 57.1% (12/21). Side effects and abnormal changes of clinical laboratory findings were observed in 5 patients, and 16 patients, respectively, but most of them were mild. The findings above suggested that the combination therapy with CZOP and TOB is useful as an empiric therapy for severe infections in patients with hematologic diseases.

[All-trans retinoic acid was effective for marked skin infiltration in a relapsed acute myelogenous leukemia (AML-M2) patient with t(12; 17)].

A 64-year-old man who had taken acute myelogenous leukemia (AML-M2) in 1989 have relapsed with t(12; 17) (p13; q11.2-21) chromosomal abnormality and presenting marked infiltration to the skin in 1994. Blasts were seen on his peripheral blood smear (15%) and bone marrow examination showed increased leukemic cells (56%), with maturation. Leukemic cells expressed CD13 and CD33 antigen but not HLA-DR. Although leukemic cells had not promyelocytic feature morphologically, detection of PML/RAR alpha infusion signal of peripheral leukemic cells were positive for 8% (1% for control) by fluorescence in situ hybridization method. Because he did not response to standard combination chemotherapy and because we considered the possibility that t(12; 17) (p13; q11.2-21) observed in this case are t(15; 17) variant, we tried all trans retinoic acid (ATRA) to him. Interestingly, ATRA was very effective for skin lesion but hematologically it had no effect at all, and he died because of bacterial pneumonia.

[Combination chemotherapy (CVP) in a patient with refractory idiopathic thrombocytopenic purpura (ITP)].

A 54-year-old woman, who had been given a diagnosis of idiopathic thrombocytopenic purpura (ITP) refractory to steroid therapy, was admitted to our hospital because of severe bleeding tendency. Splenectomy, high dose vitamin-C and interferon-alpha were not effective, although high-dose gamma-globulin had some effect. Since high-dose glucocorticoid was effective temporarily, we decided to perform chemotherapy. Seven courses of CVP chemotherapies (CVP; CPM 500 mg, VCR 2 mg, PSL 50 mg) prevented severe bleeding and did not have serious toxicity. Chemotherapy can be indicated for refractory ITP reactive to immunosuppressive therapy such as high-dose glucocorticoid.

Activation of the contact system by filtration of platelet concentrates with a negatively charged white cell-removal filter and measurement of venous blood bradykinin level in patients who received filtered platelets.

BACKGROUND: Several recent reports have described hypotensive transfusion reactions in patients receiving platelet concentrates (PCs) filtered through white cell-reduction filters. It is well known that a negatively charged surface activates the contact system, consisting of factor XII, prekallikrein, and high-molecular-weight kininogen. STUDY DESIGN AND METHODS: To clarify the mechanisms of these hypotensive reactions, the possibility that white cell-reduction filtration activates the contact system was examined. Venous blood plasma bradykinin levels were also measured in patients receiving PC transfusions through filters. RESULTS: None of the measured values were changed by filtration through a positively charged filter. However, filtration through a negatively charged filter resulted in a decrease in the amounts of prekallikrein and an increase in the amount of bradykinin generated, which indicated the activation of the contact system. The bradykinin level was inversely related to the activity of angiotensin-converting enzyme (ACE) in the PCs and was elevated by addition of an ACE inhibitor. Although the venous blood plasma bradykinin level did not change in two patients with a normal ACE activity during PC transfusion through the negatively charged filter, two patients who had decreased ACE activity, showed a significant increase in bradykinin during the transfusion. CONCLUSION: These results suggest that the generation of a large amount of bradykinin by filtration of PCs through a negatively charged filter might cause hypotensive reactions in patients with decreased ACE activity. The clinical significance of bradykinin generation requires further study.

Severe thrombocytopenia after cytomegalovirus infection in an immunocompetent host--correlation between CMV infection and platelet count in immunocompetent host.

We report a case of severe thrombocytopenia after cytomegalovirus mononucleosis and the changes of the platelet count in 13 cases (including documented case) with CMV mononucleosis (4 cases) or Epstein-Barr virus mononucleosis (9 cases), who were admitted to our hospital from 1991 to 1995. A decrease of the platelet count was observed in some patients at diagnosis compared to the following days, suggesting that thrombocytopenia may be induced by CMV as well as EBV, and mild thrombocytopenia may be more frequent than expected after CMV infection in immunocompetent adults, although severe thrombocytopenia is rare.

[Chronic myelomonocytic leukemia developed 7 years after the onset of idiopathic thrombocytopenic purpura like syndrome].

A 55-year old woman admitted to our hospital with bleeding tendency. She was diagnosed as having idiopathic thrombocytopenic purpura (ITP) by the platelet count 4.8 x 10(4)/microliter, Platelet associated IgG (PAIgG) 88.5 ng/10(7) cells, and an increase of megakaryocyte (81/microliter) of the sternal bone marrow. No obvious dysplasia of three lineages was observed. Because she did not respond to corticosteroid and gamma globulin, she was undertaken splenectomy 3 years after the diagnosis and the platelet count had been kept more than 3.0 x 10(4)/microliter during the following 2 years. After 7 years from the onset of ITP, she was admitted because of leukocytosis (16500 microliters with 8% monocytes) and thrombocytopenia (1.9 x 10(4)/microliter) with bleeding tendency. Hypercellular bone marrow with dysplasia of three lineages such as dyserythropoiesis, Pelger like nucleus, and micromegakaryocyte was observed. The chromosomal analysis presented 46XX, del (20) (q11.2) in all (50/50) cells. She was diagnosed as having chronic myelomonocytic leukemia (CMMoL). This is a difficult case in which it was distinguish ITP from refractory thrombocytopenia, a subtype of myelodysplastic syndrome. We reexamined and found some morphological abnormalities at diagnosis, suggesting that it might be preleukemic stage.

Natural killer cell frequency and serum cytokine levels in monoclonal gammopathies: correlation of bone marrow granular lymphocytes to prognosis.

The percent of granular lymphocytes of total bone marrow lymphocytes was 12.5% in controls, 15% in myeloma and 27% in monoclonal gammopathy of undetermined significance (MGUS). A good correlation was found between the percent of granular lymphocytes in the bone marrow lymphocytes at diagnosis (Y) and the years of survival (X) from the diagnosis of either the IgG- or IgA-type myeloma. The linear regression equation calculated for the IgG-type myeloma was Y = 1.6X + 7.42, and for the IgA-type myeloma Y = 4.25X + 4.75. For the purpose of analyzing in detail the granular lymphocyte behavior, two-color analyses of peripheral blood mononuclear cells and the serum levels of cytokines were performed. The absolute number of CD3+ cells, CD4+CD45RA+ cells and CD4+CD29+ cells was lower in the multiple myeloma (MM) cases than that of MGUS or controls (p < 0.01). The CD57+CD16+ natural killer (NK) cells were lower in MM cases than in MGUS cases. The serum levels of IL-1, which may activate NK cells, were higher in the MGUS cases than in either myeloma cases or controls (p < 0.01). The IL-10 levels, which may inhibit the proliferation of NK cells, were higher in the myeloma cases than in the MGUS cases (p < 0.05). Detailed understanding of the cytokine network of myeloma patients and their NK cell frequency may be important for the investigation of M proteinemias and for the future strategic planning of biological modulation therapies of myeloma patients.