Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During long-term interferon alpha-2b (IFN) therapy of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) patients, short-term effects of tumor necrosis factor alpha (TNF) on peripheral leukocyte counts, as well as cortisol and corticotropin (ACTH) release were studied. TNF (40-160 micrograms/m2) was given as a 2-h infusion on 5 consecutive days every 3 weeks, in addition to s.c. daily IFN injections (4 mio U/m2), to four (two male/two female) patients, who had been treated for more than 8 months with IFN and additionally for 0-7 months with TNF. Leukocyte counts, cortisol, and ACTH were determined at 30-min intervals between 4 p.m. and midnight. Profiles were determined the day before and on day 1 of TNF therapy. Leukocyte numbers decreased 30 min after start of TNF administration and increased 30-60 min later with a rebound until the next TNF application. The increase of leukocyte counts was due mostly to neutrophil granulocytes. ACTH levels increased 30 min, cortisol 60 min, and leukocyte counts 90 min after start of TNF infusion. Metopirone, an inhibitor of cortisol synthesis given to one patient, suppressed the TNF-induced stimulation of cortisol secretion and subsequent increase of leukocyte counts, while ACTH blood levels were enhanced. It was concluded that leukocyte count increases after TNF/IFN administration might be related to TNF-evoked cortisol secretion.
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PMID:Relation between leukocyte counts and cortisol secretion in CML patients undergoing combined TNF alpha/IFN alpha therapy. 132 78

Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment. Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.
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PMID:Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-alpha 2a and interleukin-2. 139 43

A 42-year-old male was diagnosed as having Ph-positive chronic myelogenous leukemia (CML) in 1988. He had been treated with ranimustine and interferon alpha. In April 1990, he was admitted to our hospital because of hemorrhagic diathesis. Blood counts revealed a white blood cell count of 319,200/microliters with 12 per cent blasts, a hemoglobin level of 9.2 g/dl, and a platelet count of 48,000/microliters. The bone marrow aspiration revealed hypercellularity with 68.2 per cent blasts, and chromosomal analysis showed 48, XY, +8, double Ph. A combination chemotherapy containing vindesine, cytarabine and prednisolone was administered. Four days later, he suddenly complained of headache and vertigo. CT scan of the brain showed a high density area at the cerebellar vermis. He was then treated with intensive combination chemotherapy including enocitabine, daunomycin, 6-mercaptopurine and prednisolone. He attained a hematological response and clinical improvement temporarily, as the cerebellar tumor regressed. In September he had headache and vertigo again, and CT scan revealed a rapid increase in size of the cerebellar tumor. Local irradiation with total doses of 19 Gy brought about a partial resolution of the lesion, and relief from the symptoms. In November, his hematological conditions deteriorated gradually and he died of brain hemorrhage on November 22, 1990. Post-mortem examination disclosed a 1 x 1 cm sized mass in the cerebellar vermis which showed a fibrous change surrounded with hemosiderin-laden macrophages microscopically. We reviewed the eight reported cases of CML with intracranial tumors, and discussed the factors which had contributed to the prolongation of survival in our patient.
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PMID:[Isolated cerebellar tumor formation in a patient with blastic crisis of chronic myelogenous leukemia]. 143 48

A 60-year-old man with long-standing chronic myelogenous leukemia presented with renal insufficiency and proteinuria after more than 6 years of therapy with daily interferon alpha injections. He also manifested unusual skin lesions and a low-titer antinuclear antibody (ANA). Percutaneous renal biopsy disclosed an unusual glomerular lesion characterized by global, diffuse, and marked widening of the lamina rara interna, and focal segmental mesangial proliferation. Discontinuation of the drug resulted in resolution of the proteinuria, but not the renal insufficiency. These glomerular changes have not been reported previously as a complication of this form of malignancy and are similar to lesions reported in newborn rats and mice receiving interferon alpha. The potential role of interferon alpha in the development of this glomerular disease is discussed.
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PMID:Unusual glomerular lesion in a patient receiving long-term interferon alpha. 144 66

Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.
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PMID:Chronic myelogenous leukemia: recent developments in prognostic evaluation and chemotherapy. The German CML Study Group. 160 5

Fifty percent of patients with the myelodysplastic syndrome, frequently following treatment by radiation or chemotherapy, have prognostically unfavorable deletions of the long arms of chromosomes 5 and 7, or trisomy 8, as have the 25% of patients with acute myeloblastic leukemia where remissions last 6-12 months, and where relapse cannot be prevented. In contrast, patients with prognostically favorable cytogenetics (translocation 15; 17 or 8; 21 or inversion 16) maintenance chemotherapy may prevent relapses. Of chronic myelocytic leukemia patients, 85% can achieve hematological remission with interferon alpha, and 40% a partial cytogenetic remission, which probably delays relapse.
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PMID:Prevention of chemotherapy-induced leukemia and of leukemia relapses. 172 55

Since the introduction of interferon alpha-2b (IFN alpha-2b) into clinical oncology there have been several reports dealing with acute renal failure during therapy with this new type of anticancer drug. We investigated 58 patients (pts) with myeloproliferative syndromes (56 pts with chronic myelogenous leukemia, 2 pts with essential thrombocythemia) who were treated with 4 x 10(6) IU IFN alpha-2b each day subcutaneously. In order to assess the nephrotoxic potential we used the following noninvasive methods: 1. Analysis of the excretion of 4 urinary enzymes (LDH, LAP, GGT, NAG), 2. Determination of the excretion of protein, albumin, alpha-1-microglobulin immunoglobulin G (Ig G), 3. serum creatinine. The investigations were done every 2 weeks and took 70 weeks. We found an increase in the excretion of all 4 enzymes which remained stable during the whole observation period, protein excretion was pathological in about 20% of all pts and reached values of up to 9.07 g/L alpha-1-microglobulin was excreted in pathological amounts in about 20% of all pts during the whole observation period, albumin was found in pathological quantities in about 15% of all pts and Ig G was pathologically increased in the urine in about 10% of the pts. Serum creatinine rose in 5-10% of the pts up to 1.5 mg/dL. In conclusion, IFN alpha-2b is capable of inducing combined glomerular and tubular damage. Therefore, avoiding additional nephrotoxic insults is desirable.
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PMID:Investigations on the subclinical and clinical nephrotoxicity of interferon alpha-2B in patients with myeloproliferative syndromes. 195 45

The possible synergistic interaction between azidothymidine (AZT) and interferon alpha (rIFN-alpha 2a) in the treatment of chronic myelogenous leukemia (CML) was studied in vitro using marrow or peripheral blood hematopoietic progenitors from 10 patients with CML in the mixed (CFU-GEMM) colony culture assay. Used singly, either agent inhibited erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) CML hematopoietic progenitor proliferation in a dose-dependent fashion, with the inhibitory effect being more pronounced on BFU-E than on CFU-GM colony-forming cells. The combination of both drugs in therapeutic concentrations exerted a significant synergistic inhibition on CML stem cells as assessed by the median-effect principle and isobologram equation analysis. A suboptimal dose of AZT (0.5 mumol/l) synergistically augmented the effect of rIFN-alpha 2a whereas an inactive dose of 10 U/ml rIFN-alpha 2a similarly enhanced the CML stem cell growth inhibition exerted by AZT. Our data indicate that AZT may augment the already established therapeutic benefits of IFN-alpha in CML.
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PMID:Synergistic antiproliferative effect of interferon alpha and azidothymidine in chronic myelogenous leukemia. 202 Jan 93

We describe here a patient with Philadelphia-positive chronic myeloid leukemia who had a hematologic and cytogenetic relapse after bone marrow transplantation. A diagnosis of accelerated phase was made when an additional malignant clone was detected. This clone was probably derived from the primitive Philadelphia clone, with duplication and rearrangement of the Philadelphia chromosome. The patient was treated with interferon alpha 2a and experienced a complete cytogenetic and molecular remission, with full reconstitution of the donor marrow.
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PMID:Interferon alpha treatment of accelerated-phase chronic myeloid leukemia in relapse after bone marrow transplantation: a case with complete cytogenetic and molecular remission. 204 79

In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon alpha instead of busulfan prolongs the chronic phase of Philadelphia-positive CML. Additional goals are the examination, 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 September 5, 1990, 593 CML-patients had been randomized, 221 for busulfan, 228 for hydroxyurea and 144 for interferon alpha. The average age is about 51 years. By April 30, 1990, 106 patients had reached the end of the chronic phase, 126 had died. The median survival of Philadelphia-positive patients was 3.95 years, that of all patients 3.75 years. The median observation time of all patients was 1.34 years (mean 1.60 years). At present, no significant difference in survival is recognizable between the three treatment arms, although fewer adverse effects have been observed in the hydroxyurea arm.
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PMID:[Multicenter prospective controlled study of therapy of chronic myeloid leukemia. Comparison of busulfan, hydroxyurea and interferon alpha (April 1990 status)]. 205 76


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