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  • 1
    ISSN: 1569-8041
    Keywords: cladribine ; 2-chlorodeoxyadenosine ; chronic lymphocytic leukaemia ; infection ; myelotoxicity ; remission duration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To study the efficacy and the safety of cladribine (2-chlorodeoxyadenosine, 2-CDA) administered as 24-hour infusions or as subcutaneous bolus injections at two different doses to patients with relapsing or refractory chronic lymphocytic leukaemia (CLL). Patients and methods: In this non randomised 2-cohort study, 20 patients with pretreated CLL received cladribine at a dose of 0.7 mg/kg/cycle as continuous i.v. infusions over seven days (group 1) and 35 patients were treated at a reduced dose of 0.5 mg/kg/cycle given as s.c. bolus injections for five days (group 2). After two cycles of four week duration, response was assessed. In the case of progressive disease, therapy was discontinued, otherwise a maximum of four additional cycles were administered until best response. Results: A total of 130 cycles were administered (group 1: 41, group 2: 89). Patient characteristics in both groups were comparable. The median dose intensities were 0.172 mg/kg per week and 0.123 mg/kg per week for groups 1 and 2, respectively (P ≤ 0.0001). The overall response rate for all 55 patients was 38% (95% confidence interval (95% CI): 25%–52%), with 5% CR and 33% PR. Response was similar in both patient groups (35% in group 1, 40% in group 2). No association between cladribine dose intensity and response rate was found, and there was no difference between patients relapsing after or refractory to previous therapies (11 of 24 vs. 10 of 31). Median remission duration was six months in both groups. Toxicity, in particular infections (all WHO grades, 34% in group 1 versus 7% in group 2) and myelosuppression (grade 1–4 neutropenia, 72% versus 41% of cladribine cycles) were statistically significantly more frequent in group 1. Conclusion: Cladribine is active in heavily pretreated patients with chronic lymphocytic leukaemias. Dose reduction by 29% led to similar response and remission duration, but to a significant decrease of myelotoxicity and risk of infection. Cladribine administered as s.c. bolus injections at 0.5 mg/kg per cycle is safe and this dose level should not be exceeded in this patient population.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Cytokines ; IL-3 ; SAA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 37-year-old woman with severe aplastic anemia (SAA), who had relapsed 6 years after antilymphocyte globulin therapy, was treated with intravenous recombinant human IL-3 (4μg/kg/d) for 21 days. Subsequently, long-term therapy with subcutaneous rhIL-3 at the highest dose level tested so far (16μg/kg/kg/d) was initiated in order to maintain growth-factor response. Therapy was discontinued on day 73 due to progressive thrombocytopenia and increased petechial bleeding. Both treatment schedules resulted in a transient increase in leukocytes (twofold) due to an increase in monocytes, neutrophils, and eosinophils. RhIL-3 had no effect on hemoglobin values or platelet counts and only marginally improved colony formation of bone marrow CFU-GM in response to rhGM-CSF. Side effects of both treatment schedules were mild and did not exceed WHO grade II. Steady-state serum concentrations of IL-3, which are able to stimulate hematopoiesis in vitro (i.e.〉1 ng/ml), were achieved by both low- and high-dose treatment, although high-dose treatment resulted in markedly higher serum levels of IL-3. On measuring cytokine serum levels (neopterin, IL-1β, IL-6, sIL-2R, GM-CSF, TNF-α, IFN-γ) we noticed a different cytokine pattern with both treatment modalities, resulting in a moderate induction of TNF-α and IFN-γ during low-dose, intravenous treatment, whereas during subcutaneous, high-dose treatment a profound increase of IL-6, sIL-2R, and, to a lesser extent, neopterin was detected. These results in a single patient with SAA indicate that further studies on IL-3 serum levels and IL-3-induced secondary cytokines in a larger group of patients are needed to optimize growth-factor treatment and to better understand the in vivo biological activity of IL-3.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Key words Anti-lymphocyte globulin ; Neutropenia ; T-large granular lymphocyte leukemia ; Granulocyte-colony stimulating factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Optimum treatment of severe neutropenia, a major factor for morbidity and mortality in T-large granular lymphocyte (LGL) leukemia, is undefined. We observed a rapid improvement of the neutrophil count in a patient with T-LGL leukemia and severe neutropenia after the combined administration of anti-lymphocyte-globulin (ALG), cyclosporin A, prednisone, and granulocyte colony-stimulating factor (G-CSF). Although G-CSF treatment was terminated after 7 days, the neutrophil count has persisted above 1.0×109/l for up to 6 months now. Oral methotrexate is given continuously as treatment for T-LGL leukemia. The response to this immunosuppressive regimen suggests a T-cell-mediated mechanism as the underlying cause for neutropenia in T-LGL leukemia.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Key words Allogeneic bone marrow transplantation ; Granulocytic sarcoma ; Chloroma ; Leukemia ; Myelodysplastic syndrome ; Relapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Of 229 consecutive patients receiving allogeneic blood or bone marrow stem cell transplants for acute myeloid leukemia, chronic myeloid leukemia, or myelodysplastic syndrome between 1974 and 1996, 52 patients relapsed. The original tumor recurred as granulocytic sarcoma (chloroma) in three patients (1.3%). Chloroma was found in the ovary in two patients and in the central nervous system in one patient. None of these three patients had experienced ≥ grade II acute or more than limited chronic graft-versus-host disease. The intervals between transplantation and recurrence with chloroma were 2, 6, and 13 years. Two patients received a second transplant, and all three died of treatment sequelae.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0584
    Keywords: Key words MTS1 ; p16 ; Tumor suppressor gene ; Leukemia ; Prognostic factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  MTS1, a tumor supressor gene located on chromosome 9p21, has been shown to be altered in a number of human tumor cell lines, primary solid tumors, and leukemias. In this study we found low expression of MTS1 in lymphocytes from seven of nine healthy donors, but in none of eight granulocyte samples from the same controls, suggesting a physiological role of MTS1 in peripheral blood cells capable of proliferation, but not in end-stage differentiated cells. We detected MTS1 mRNA expression in 38 of 57 patients (66%) with acute myelogenous leukemia (AML) treated in a standardized clinical protocol. No deletion of the MTS1 gene was found in any of the AML samples tested. There was no significant association between expression of MTS1 and response to therapy, progression-free, or overall survival. Except for a negative correlation between MTS1 level and leukocyte count at diagnosis (p=0.03), there was also no association with any of the known prognostic parameters in AML. We conclude that MTS1 shows a significantly higher expression in leukemic than in normal peripheral blood cells, that deletion of MTS1 is not a frequent event in AML, and that its expression is not significantly correlated with outcome of the disease.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 79 (2000), S. 312-318 
    ISSN: 1432-0584
    Keywords: Key words Essential thrombocythemia ; Polycythemia vera ; Osteomyelofibrosis ; Thromboembolism ; Hemorrhage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This retrospective single-center study compared thromboembolic and hemorrhagic complications, survival and causes of death in a cohort of 102 consecutive patients with myeloproliferative disorders (MPD). We included 17 patients with essential thrombocythemia (ET), 59 with polycythemia vera (PV), and 26 with osteomyelofibrosis (OMF). The median follow-up was 3.7 years. Estimated 8-year probability of complications for the entire cohort was 80 ±11% (95% confidence interval), without significant differences among MPD subgroups. The rate of thromboembolic complications, expressed as the number of events per 100 patient years, was 16.7 for patients with PV, 13.8 for OMF, and 7.5 for ET. Fifty-four percent of thromboembolic events in PV involved cerebral or limb arteries. The rate of bleeding complications was highest in patients with OMF (31.8 per 100 patient years), followed by ET and PV (11.8). Ninety percent of bleeding episodes affected the skin, mucosal membranes, and the gastrointestinal tract. Eight-year survival was highest in ET with 91±17%, followed by PV (66±18%) and OMF (40±31%) (P〈0.01). Twenty-four patients died during the observation period, and fatal thrombosis (in five patients) represented the leading cause of death. Only two patients with MPD died from fatal hemorrhage and one from acute leukemia. We conclude that survival is highest in ET and lowest in OMF. Both thromboembolic and hemorrhagic complications are frequent. However, thrombosis appears to be more often fatal than bleeding complications. Prophylaxis of thromboembolic events remains a key issue in the management of MPD.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 56 (1988), S. 79-81 
    ISSN: 1432-0584
    Keywords: Aplastic anemia ; Leukemia ; Bone marrow morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We describe a patient with acute myeloid leukemia (AML) occurring 5 years after successful treatment of severe aplastic anemia (SAA) with antilymphocyte globulin (ALG). Four years after ALG, SAA had relapsed. A second remission of SAA was achieved, but was followed by transformation of the myelodysplastic syndrome into overt AML. After 2 courses of high-dose cytosine arabinoside and VP-16 complete remission occurred. This case shows that chemotherapy of secondary leukemia after SAA is feasible, and that ex-aplastic bone marrow is capable of complete recovery from chemotherapy-induced aplasia. Morphological anomalies of bone marrow noticed early during remission of SAA might predict a late transformation in leukemia.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: CML ; Busulfan ; Hydroxyurea ; Interferon-alpha ; Duration of chronic phase ; Prospective study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0584
    Keywords: rIFN alpha-2a ; Thrombocytosis ; Myeloproliferative disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an open prospective pilot trial, we tested the effect of recombinant interferon alpha-2a (rIFN alpha-2a) on thrombocytosis in myeloproliferative disorders (MPD). Since October 1986, 13 patients with MPD (4 with chronic granulocytic leukemia, 4 with polycythemia vera, 3 with essential thrombocythemia and 2 with myeloid metaplasia) were treated with rIFN alpha-2a. Platelet counts decreased in all treated patients within 2 to 10 weeks from a median value of 1,050×109/l (range 610−1,940×109/l) to 340×109/l (range 230−495×109/l). The response was dose-dependent. In 11 patients we observed a simultaneous reduction of the white blood cell count. Six patients still continue the IFN alpha-2a therapy. In 7 treatment was discontinued, because of chronic side effects in 3, and because of noncompliance in one. In these patients, thrombocytosis recurred after discontinuation of the therapy. These results show that rIFN alpha-2a is effective in controlling thrombocytosis in MPD. However, the long-term benefit of interferon in these disorders remains to be established.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 60 (1990), S. 255-256 
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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