摘要:

The objective of this study was to assess the pharmacokinetics of rhG-CSF after a single intraperitoneal injection 2 h post-TBI in B6D2F1 lethally irradiated mice and to analyze the effect of rhG-CSF on the endogenous response of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in these animals. For comparison, these cytokine serum levels have also been measured in nonirradiated mice. The serum concentrations of rhG-CSF in irradiated mice were higher than in nonirradiated mice at all time points during the first 60 min after injection. Furthermore, rhG-CSF administration failed to induce detectable endogenous serum levels of IL-3, IL-6 and GM-CSF, at least in the 72-hour period after administration of the rhG-CSF. The radioprotective effect of rhG-CSF in lethally irradiated mice is not mediated by an increase in endogenous serum levels of these three cytokines.

ISSN:0001-5792    

DOI:10.1159/000203604

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We have treated 9 patients with sickle cell anemia (SS) with hydroxyurea (HU). All 9 patients carried 4 α-globin genes and the βs globin haplotypes 19/ 19 (Benin/Benin), except for 1 who had haplotype 19 together with type 3 (Benin/Senegal). Six patients received HU for 10 months and were again treated with the drug for 5 months after an interval of 1 year. One patient was given HU for 22 consecutive months. A record was kept of hematological and biochemical data, Hb F and Gγ levels, as well as possible clinical complications. Our data show that HU generally improves the hematological and biochemical values and the level of Hb F, and reduces painful crises in some patients. However, although the clinical symptoms improved in some patients during HU therapy, the older patients did not observe any changes in their general condition; the same is the case for the patient with haplotype 19/3. One patient also experienced life-threatening liver sequestration during treatment. We conclude that the selection of patients who may benefit from HU therapy needs further evaluati

ISSN:0001-5792    

DOI:10.1159/000203605

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Elderly patients with non-Hodgkin’s lymphoma (NHL) were treated with cyclophosphamide, vincristine, prednisone, bleomycin, Adriamycin, procarbazine (COP-BLAM) therapy at our institution. Prognostic factors were analyzed in 62 patients with untrated NHL aged 65 years or older. Of these patients, 47 (75.8%) achieved a complete remission and 11 (17.7%) partial remission. The overall response rate was 93.5%, with a 5-year survival rate of 70%. Factors with prognostic significance included age, performance status, albumin, stage, B symptoms, and histologic type according to the International Working Formulation. Of the 62 patients, 26 were alive at the time of writing. Of the 36 patients who died, 30 died due to progression of NHL or treatment-related disorders, and 6 died from disease other than NHL. Some of the prognostic factors identified in these elderly patients are not included among the prognostic factors reported for younger patients, suggesting the need to individualize chemotherapy for NHLs of different types, which can be defined by prognostic factors. Prognostic factors other than age should be taken into account, particularly when doses and dosing intervals are determine

ISSN:0001-5792    

DOI:10.1159/000203606

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The combination of cyclophosphamide (CY) and etoposide is synergistic, spares bone marrow stem cells and can be given repeatedly in high doses without stem cell support. Thirteen patients with non-Hodgkin’s lymphoma (n = 8) or Hodgkin’s disease (n = 5), received high-dose chemotherapy (HDC). Median age was 32 years (24-52). Male to female ratio was 10:3. All the patients were in advanced stage. Karnofsky score prior to HDC was 60% (range 40-90). Six patients showed primary refractoriness and 7 had resistant relapse. HDC consisted of CY 1,500 mg/m2/day and etoposide 300 mg/m2/ day, both for 4 days. rhG-CSF was started 24 h after the last dose of chemotherapy as a continuous intravenous infusion at a dose of 0.01 mg/kg/day and stopped when the leukocyte count reached 1 × 109/1 on 3 consecutive days. Overall, 69% (9/13) of patients responded to HDC. Four achieved CR and 5 achieved PR. Two of the patients showed disease progression. The other 2 died during the early period of HDC. Neutrophil and platelet recovery after HDC were 8 (6-16) and 10 (4-14) days, respectively. The major nonhemato-logical toxicities were nausea-vomiting (100%) and diarrhea (61%). The median follow-up was 204 (7-600) days. Two patients relapsed 48 and 185 days after HDC. Eight patients are still alive, 7 progression free. The progression-free survival is 220 (40-285) days. In conclusion, HDC+granulocyte colony-stimulating factor (G-CSF), without stem cell support seems to be promising in refractory or resistant relapse lymphoma patients bringing the need for randomized studies to show the cost effectiveness of HDC+G-CSF compared to HDC+ autologous stem cell sup

ISSN:0001-5792    

DOI:10.1159/000203607

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Vesnarinone, an oral therapeutic agent for cardiac failure, causes agranulocytosis as a side effect. To elucidate the mechanism of occurrence of the agranulocytosis, we examined the effect of vesnarinone on granulopoiesis using an in vitro human long-term bone marrow culture system. Addition of vesnarinone to the culture decreased the total number of hematopoietic cells, mainly composed of mature granulocytes and macrophages, but increased the number of granulocyte-macrophage progenitor cells (CFU-GM) and CD33-CD34+ cells as compared with an untreated control. Differentiation of CFU-GM was induced by removing the agent from the culture medium, indicating that the effect of vesnarinone was reversible. The agent did not directly affect CFU-GM in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, treatment of stromal cells with vesnarinone repressed the production of G, GM, M-CSF, suggesting that the agent may cause a hematopoietic disorder, agranulocytosis, through the impairment of stromal cell function.

ISSN:0001-5792    

DOI:10.1159/000203608

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Erythropoietin levels were determined in 50 Greek females: 20 beta-thalas-saemia (beta-thai) heterozygotes, 15 with a diagnosis of iron-deficiency anaemia and 15 normal controls. In beta-thai trait carriers, the erythropoietin levels were slightly higher than in normal controls (16.65 ± 4.43 vs. 12.84 ± 2.47 mU/ml); these levels were significantly lower than those in iron-deficient subjects with the same degree of anaemia (55.24 ± 31.35 mU/ml). In both groups, the erythropoietin levels are statistically correlated with the severity of anaemia (r = -0.537 p < 0.05 for iron deficiency; r = -0.610 p < 0.01 for beta-thai heterozygotes). In beta-thai heterozygotes, a close inverse correlation with red cell number and erythropoietin levels was also noted. It is suggested that microcytosis accompanying beta-thai trait constitutes an additional factor intervening in the regulation of erythropoies

ISSN:0001-5792    

DOI:10.1159/000203609

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

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.

ISSN:0001-5792    

DOI:10.1159/000203610

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Chronic myelogenous leukemia (CML) is a clonal disorder starting with a chronic phase and progressing to an acute blastic phase. Philadelphia (Ph) chromosome formation results in the relocation of the ABL oncogene from the chromosome 9q34 to BCR region on 22qll, forming the BCR/ABL fusion gene. The Ph chromosome once detected rarely disappears, except as a result of therapy. We present an unusual Ph-positive CML case, which developed lymphoid blast crisis in complete cytogenetic remission following interferon-α and hydroxyurea therapy. Sequential cytogenetic investigations were carried out on bone marrow. After a standard Ph translocation seen at diagnosis, from the 8th month of therapy all metaphases showed a normal diploid karyotype. Fluorescence in situ hybridization detected residual BCR/ABL-positive inter-phase cells during the 12th month of therapy. In the 14th month, the patient showed 27% blasts in marrow though normal cytogenetics was maintained. Present findings suggest blastic transformation occurred in a Ph-negative lymphoid clone. This supports the hypothesis that an actual leukemogenic event occurs in a multipotent stem cell prior to the acquisition of Ph translocation

ISSN:0001-5792    

DOI:10.1159/000203611

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Lysinuric protein intolerance (LPI) is an inborn error of amino acid transport characterized by a wide spectrum of clinical and biochemical abnormalities. Bone marrow hemophagocytosis in this disorder is an intriguing finding, present mostly in Italian patients. We report a 19-month-old Turkish infant with LPI, bone marrow hemophagocytosis, interstitial lung disease and immunological abnormalities unprecedented in the current literature. Possible etio-logic factors responsible for hemophagocytosis and the differential diagnosis of hemophagic syndromes are discussed.

ISSN:0001-5792    

DOI:10.1159/000203612

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Chronic neutrophilic leukemia (CNL) is a rare hematologic disorder usually presenting with a persistent neutrophilia in the leukemoid range (WBC > 40-50 × 109/1) and consisting largely of mature neutrophils. Patients have no obvious cause for an elevated white count and typically have an elevated leukocyte alkaline phosphatase score, hepatosplenomegaly, elevated vitamin B12 and are Philadelphia chromosome-negative. CNL has occasionally been associated with paraproteinemia or outright myeloma. Dysplastic features within the neutrophils in CNL have rarely been reported. We report the clinical, pathological and cytogenetic features of a case of CNL in an elderly white female initially diagosed with refractory anemia with excess blasts, which subsequently progressed to CNL

ISSN:0001-5792    

DOI:10.1159/000203613

出版商:S. Karger AG    

年代:1997

数据来源: Karger