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)

Cytogenetic effects of busulfan in vitro were studied in normal bone marrow (nine cases) and Philadelphia chromosome (Ph)-positive cells (10 cases) of patients with chronic myeloid leukemia. The frequency of chromosome aberrations and sister chromatid exchange (SCE) increased dose dependently. While there were no significant differences between normal and leukemic cells with regard to the induction of chromosome aberrations, the frequency of SCE was significantly lower in Ph-positive cells than in normal bone marrow. This difference was not only apparent on the basis of the SCE frequency per cell, but also when the SCE frequency was correlated to the relative chromosome length as shown by the SCE rate per chromosome group. Longitudinal studies of three patients who received long term busulfan treatment did not show a significant change in the frequency of induced SCE. It can be suggested that the lower frequency of induced SCE in Ph-positive cells reveals less sensitivity of the leukemic cells to DNA damage by busulfan. Our data provide evidence for the inability of busulfan treatment to eradicate or even reduce Ph-positive cells in chronic myeloid leukemia. Evaluation of cell proliferation by sister chromatid differentiation shows longer cell cycle times for the Ph-positive cells. Busulfan affected the cell cycle duration of leukemia and normal cells very little.
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PMID:Induction of sister chromatid exchanges and chromosomal aberrations by busulfan in Philadelphia chromosome-positive chronic myeloid leukemia and normal bone marrow. 316 16

Patients in the stable phase of chronic myelogenous leukemia (CML) are usually treated with busulfan. The bone marrow of patients with CML may be exquisitely sensitive to busulfan, and occasionally such patients develop pancytopenia, secondary to hypoplasia or aplasia of the bone marrow, which is presumed to be due to busulfan-induced marrow toxicity. We report a case of Philadelphia chromosome-positive CML who developed pancytopenia while being treated with busulfan; however, the patient's bone marrow was not hypoplastic or aplastic but rather hyperplastic with sideroblastic changes. Busulfan is not known to cause sideroblastic changes, so this was considered to herald a transformation into acute leukemia. Busulfan was stopped, and only supportive treatment was given. To our surprise approximately 22 weeks after busulfan was stopped, the sideroblastic changes had disappeared and the bone marrow again showed features of CML. This case suggests that busulfan may cause sideroblastic anemia.
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PMID:Busulfan-induced sideroblastic anemia. 316 1

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high-risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.
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PMID:Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. 331 Dec 3

A 61-yr-old man with chronic myelocytic leukemia treated continuously for 8 yr with busulfan presented with fever, abdominal pain, and elevated liver enzymes in a cholestatic pattern. Evaluation of his liver and biliary tract with ultrasound and computerized tomography disclosed no structural abnormality. A percutaneous needle liver biopsy revealed cellular cholestasis with focal liver cell necrosis accompanied by a mild inflammatory infiltrate. Busulfan was discontinued, with subsequent normalization of liver enzymes and resolution of fever. These findings are interpreted as being compatible with busulfan-induced hepatitis.
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PMID:Busulfan-induced hepatitis. 337 24

Studies of the effect of interferon on the growth of colonies of myeloid leukemic blast cells, myeloma colony-forming cells, and normal hemopoietic precursor cells have demonstrated that interferon shows no specificity in inhibiting the growth of these cells in culture (ie, growth of the malignant and normal precursor cells is equally inhibited). However, interferon markedly reduces the self-renewal capacity of acute myeloid leukemic blast cells and myeloma cells. This observation suggested that interferon's ability to prolong rather than induce remissions should be tested. We have studied the ability of interferon alfa-2b (Intron A) to prolong remissions induced by busulfan (Myleran) in patients with chronic granulocytic leukemia (CGL). The leukocyte doubling time and remission duration among patients receiving no therapy was compared with the values observed during interferon alfa-2b maintenance therapy. Nine patients have begun the study; five have completed 3 months of interferon alfa-2b therapy. In four (80%) of the five patients, there has been a significant slowing of the leukocyte doubling time and prolongation of the remission duration. A larger study, with longer follow-up, will be required to determine whether interferon alfa-2b therapy will slow progression of CGL to the blast phase and prolong survival.
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PMID:Interferon alfa-2b in the treatment of chronic granulocytic leukemia. 346 99

Busulfan or Misulban is considered by many the treatment of choice in chronic myeloid leukemia, for which it is used as a single agent. An interstitial fibrosing lung disease occurring after Busulfan was first described in 1961 and to date 56 cases have been published and are the object of this review. The clinical picture of this drug induced disease is well characterised. The disorder has an estimated incidence of 6% and begins gradually, marked by non-specific signs (dyspnoea, cough) and by an alteration in the clinical state, often severe, and is frequently accompanied by skin pigmentation. As a rule it occurs after prolonged treatment (on average 41 months, cumulative dose 2.900 mg). The respiratory function pattern is that of an interstitial fibrosis characterised by reduced volumes and hypoxaemia and hypocapnic respiratory failure. The radiology reveals interstitial and predominantly basal shadows. The histology is often obtained, either by lung biopsy or frequently at necropsy, because the prognosis is poor with an 84% mortality from respiratory failure. As for numerous interstitial pneumopathies, it poses questions as to the pathogenesis and early detection, problems which at present are imperfectly resolved.
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PMID:[Busulfan-induced pneumopathy]. 347 80

A 55-year-old woman was diagnosed as having chronic myeloid leukemia in 1961. After 9 years with stable white blood cells, progression of the disease was noted (white cells up to 180 X 10(9)/l; splenomegaly to the umbilicus). Busulfan was given over 4 weeks resulting in a remission of 13 years duration. Progression was observed again in 1983, 22 years after the initial diagnosis of chronic myeloid leukemia. Therapy with hydroxyurea resulted in another remission of shorter duration. Two chromosome studies showed the Philadelphia chromosome in 100% of metaphases without additional aberrations. In 1985 blast crisis developed. The cause of death as determined at autopsy was an undiagnosed miliary tuberculosis. The presented case is of special interest since (1) it is a report of the longest surviving patient with chronic myeloid leukemia, and (2) in contrast to other cases with long survival, this patient did not show chromosomal mosaicism or any additional chromosomal aberrations.
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PMID:[24-year survival in chronic myeloid leukemia]. 347 6

The retrospective analysis of 40 cases with chronic granulocytic leukemia revealed an average survival time of 39 months. Modal proportions between the chronic, accelerated and acute blastic crisis amounted to 25:6:8 months. The characteristic points and curves for peripheral white cell, blast cell, basophil cell and thrombocyte counts as well as haemoglobin levels were determined separately in 20 patients with long and in 20 with short survival time. Comparisons indicate among others that Busulphan sensitivity is an essential factor for a longer survival time of CGL patients.
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PMID:Econometric analysis of phase duration for blood morphology and basophil count alterations in chronic granulocytic leukaemia. 620 49

Busulfan kinetics were studied in patients with chronic myelocytic leukemia after oral doses of 2, 4, and 6 mg. The plasma concentration-time data could be fitted to a zero-order absorption one-compartment open model. The elimination rate constant averaged 0.27 +/- 0.05 hr-1 (SD). The plasma AUC was linearly related to the dose. The lag time for the start of absorption, the time absorption ends, and the absorption rate constant showed some interindividual variations. About 1% of busulfan is excreted unchanged in urine over 24 hr.
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PMID:Busulfan kinetics. 657 31

A transplantable granulocytic leukemia (GL-13-BC) in strain 13 guinea pigs, which has many similarities to human CML, was used to test the antineoplastic effects of two alkylating agents, busulfan and cyclophosphamide, administered in the late and early stages of the disease. Busulfan had a pronounced cytoreductive effect on circulating leukemic cells in the late, pre-blast crisis stage of this disease but all treated animals, succumbed to the leukemia with only a marginal increase in survival time relative to that of untreated controls. In this respect the guinea pig model resembles human CML. Survival time was moderately increased with early busulfan treatment but, as in the late treatment group, all animals succumbed to the leukemia. A pronounced cytoreductive action on leukemic cells was also observed in guinea pigs treated with cyclophosphamide. Late treatment with this drug produced highly variable effects on the survival time of leukemic guinea pigs; of the nine animals treated, no effect was observe in five, three showed a significant increase in survival time and one animal was still in remission without treatment when the experiment was concluded. Early treatment with cyclophosphamide produced the most striking finding of this study. Two treatments with this drug produced a complete remission in all of the treated guinea pigs. This remission lasted without further treatment for the duration of the study (greater than 200 days) while all untreated controls died within 27-37 days after receiving leukemic cell transplants. The relevance of these findings to the treatment of human CML is discussed.
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PMID:Busulfan versus cyclophosphamide treatment in the early and late stages of granulocytic leukemia in guinea pigs. 659 77


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