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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 65 (1987), S. 706-712 
    ISSN: 1432-1440
    Keywords: Hairy-cell leukemia ; Interferon gamma ; Interferon alpha-2b
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 6 Patienten mit einer Haarzellenleukämie wurden 3–35 Monate nach Splenektomie mit IFN-γ (4 × 106 E/m2/2. Tag sc) behandelt. Während einer Therapiedauer von 9–35 Wochen konnte bei keinem Patienten eine signifikante klinische oder hämatologische Befundbesserung erzielt werden. Nach einem therapiefreien Intervall von 0–13 Wochen erhielten alle Patienten IFN-α-2b (zunächst 4 × 106 E/m2/2. Tag, Erhaltungstherapie 1 × 106 E/2. Tag). Zum Zeitpunkt der Beendigung der jeweiligen IFN-α-2b-Gabe war bei 5 von 6 Patienten (1 Patient mit postthrombotischem Syndrom verstarb an einer Lungenembolie) eine deutliche Befundbesserung eingetreten. Nach einer Beobachtungszeit von jetzt 9–14 Monaten konnten 1 CR, 3 PR und 1 MR induziert werden. Die Nebenwirkungen beider Interferon-Präparationen unterschieden sich nicht signifikant.
    Notes: Summary Six patients with hairy-cell leukemia were treated with gamma-(IFN-γ) and alpha-(IFN-α-2b) interferon; 3–35 months following splenectomy, treatment was started with 4 × 106 U/m2 IFN-γ sc (iv) every second day for 9–35 weeks. Although the white blood cell counts decreased during therapy from 4.1–49 × 109/1 to 1.5–43 × 109/1, no hematological or clinical improvement was obtained. Subsequently (interval 0–13 weeks), IFN-α-2b was given at an initial dose of 4 × 106 U/m2 sc every second day to all patients. After a treatment period corresponding to that of IFN-γ administration, a significant hematological improvement was observed in five patients (one early death due to pulmonary embolism). At the last follow-up (9–14 months after start of treatment; maintenance therapy, 1 × 106 U every second day), these patients exhibited normal peripheral blood cell counts, and in bone marrow biopsy specimens a marked decrease of hairy cells was seen (1 CR, 3 PR, 1 MR). Adverse reactions including fever, headache, nausea, dryness of the mouth, myalgia, and fatigue did not significantly differ between the two interferon preparations. Whereas IFN-γ is unlikely to have any significant impact on the course of hairy cell leukemia, IFN-α-2b does result in improvement of hematological values and well-being in almost all patients.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 63 (1985), S. 1081-1082 
    ISSN: 1432-1440
    Keywords: Cyclosporin A ; interleukin 2 ; etoposide ; drug interaction ; T-lymphocytic leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0584
    Keywords: Interferon alpha ; Interferon gamma ; Chronic myelogenous leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Key words CML ; Myelofibrosis ; Dynamics ; Megakaryocytes ; Morphometry ; Interferon ; Busulfan ; Sequential bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph1+-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0584
    Keywords: CML ; Myelofibrosis ; Dynamics ; Megakaryocytes ; Morphometry ; Interferon ; Busulfan ; Sequential bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph1+-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-7339
    Keywords: Key words Opioid therapy ; Tolerance ; Adverse effects ; Insufficient analgesia ; Opioid change
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The charts of 273 cancer patients were retrospectively analyzed in order (1) to evaluate the frequency of opioid change (OCH) when adjuvants (antiemetics/laxatives) were administered on a regular basis and co-analgesic medication as indicated by the specific type of pain, (2) to define risk factors for the request of OCH, and (3) to reveal settings in which OCH may not be recommended as a first-line therapeutic intervention. Opioids used included morphine, fentanyl, l-methadone, and buprenorphine. Out of 273 patients, 103 changed opioids at least once, with a success rate of 65%. The indications for the OCH were insufficient analgesia in 43%, intolerable side effects in 20%, both in 15%, and other reasons in 22% of patients. The frequency of OCH was not influenced by the routine use of adjuvants or co-analgesics except corticosteroids, which raises queries about the concept of an opioid-sparing effect of co-analgesics. The occurrence of intolerable side effects is thought not to be dose dependent so much as to reflect differences in the individual tolerability of a distinct opioid for whatever reason (genetically fixed or individually acquired pharmacodynamic or kinetic properties). Moreover, there was strong evidence for the existence of an unpredictable and incomplete cross-tolerance between opioids, which meant careful titration of the new opioid was required after OCH. The overall frequency of OCH was similar to that observed in previous studies in spite of the documented addition of adjuvants and co-analgesics. This retrospective study supports the notion that opioid rotation must be retained as an essential therapeutic option even with optimized adjuvant and co-analgesic regimens.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7217
    Keywords: chemotherapy ; endocrine maintenance therapy ; medroxyprogesterone acetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3‐weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent‐to‐treat analysis (p=0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p=0.012). Seven patients were removed from MPA due to side effects. The changes in patient‐rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p=0.39). In conclusion, in patients with advanced breast cancer achieving remission or non‐progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.
    Type of Medium: Electronic Resource
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