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)

Twenty-seven patients with chronic myelogenous leukemia (CML)--17 in the chronic phase and 10 in the accelerated phase--were treated with an intensive chemotherapy regimen consisting of idarubicin, arabinosylcytosine, and etoposide. All patients were ineligible for bone marrow transplantation (BMT) and showed little or no cytogenetic response to interferon alpha (IFN-alpha). Blood hemopoietic cells (BHC) were collected by leukapheresis in all patients during early recovery from chemotherapy-induced aplasia. In 13/27 patients (48%), all metaphases were Ph-negative (Ph-); in another five patients, the percentage of Ph-positive (Ph+) metaphases decreased to less than 50%. Complete Ph+ disappearance was found in 66% of the patients treated within two years of diagnosis and in only 30% of those treated later. The collected Ph- cells have been used as autotransplants in nine patients: seven have shown sustained engraftment, and five are alive and well, with Ph- at 3+, 4+, 7+, 11+, and 19+ months after transplant. It is remarkable that one patient, now Ph- at 19 months after transplant, is also PCR negative. These results suggest that it is possible to collect Ph- hemopoietic cells even years after diagnosis and to perform autologous transplants with these cells.
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PMID:Selective overshoot of Ph-negative blood hemopoietic cells after intensive idarubicin-containing regimen and their repopulating capacity after reinfusion. 790 25

The influence of 2-CDA and interferon alpha (IFN-alpha) on the CFU-GM cells from ten normal individuals as well as on the CFU-GM from ten patients with chronic myeloid leukemia (CML) and on clonogenic leukemic blasts (CFU-L) from ten patients with acute myeloid leukemia (AML) in semi-solid cultures in vitro was investigated. The agents were added to the cultures alone and in combinations at concentrations of 20, 40 and 80 nM/l of 2-CDA and 10(2), 10(3) and 10(4) U/ml of IFN-alpha. A dose-dependent growth inhibition of CFU-GM as well as of CFU-L was observed. The inhibitory effect of both drugs used alone was significantly greater on the CFU-GM cells from patients with CML than on cells from normal donors. However, 2-CDA and IFN-alpha used together showed greater additive effect on the CFU-L than on the CFU-GM from normal donors and from CML patients.
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PMID:The interaction of 2-chlorodeoxyadenosine (2-CDA) and interferon alpha (IFN-alpha) on normal and myeloid leukemia hematopoiesis in vitro. 790 73

Only a minority of patients with chronic myeloid leukaemia (CML) benefit from allogeneic bone marrow transplantation (BMT), a potentially curative therapy, or from treatment with interferon alpha, which prolongs survival in cytogenetic responders. In Genoa a programme has been initiated in which CML patients are autografted with Ph-negative peripheral stem cells. To assess the pattern of marrow reconstitution, we studied the clonality of haemopoiesis in five females who engrafted and were Philadelphia chromosome negative. This was performed by evaluating the methylation patterns of the X-linked hypervariable DXS255 locus with the probe M27 beta. All four analysable women showed polyclonal methylation patterns in both granulocytes and T lymphocytes, suggesting that marrow reconstitution occurred from normal residual stem cells.
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PMID:Restoration of normal polyclonal haemopoiesis in patients with chronic myeloid leukaemia autografted with Ph-negative peripheral stem cells. 798 32

The myelodysplastic syndrome (MDS) and myeloproliferative syndrome (MPS), together with chronic lymphatic leukemia (CLL) are, for the most part, seen in the elderly. Chronic myeloid leukemia (CML), however, is not common in this age group. New treatment for the myelodysplastic syndrome is the use of cytokines, for CLL fludarabine, and 2-chloro-2-deoxy-adenosine (2-CDA). The standard form of treatment for CML and other myeloproliferative syndromes is interferon alpha or hydroxyurea, or a combination of the two.
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PMID:[Leukemias in advanced age. Part 2: Myelodysplastic syndrome and chronic leukemia]. 802 Aug 58

Incubation of chronic myeloid leukemia (CML) marrow for 10 days in vitro causes a marked and selective loss of very primitive Philadelphia chromosome (Ph)+ as compared with Ph- progenitors. We have autografted 22 patients with CML (16 in first chronic phase [group 1] and 6 with more advanced disease [group 2]) with marrow treated in this way to facilitate restoration of Ph- hematopoiesis after intensive therapy. Hematologic recovery to greater than 0.5 x 10(9)/L neutrophils occurred in 16 patients, and to greater than 20 x 10(9)/L platelets in 15 of 21 evaluable patients at a median of 29 and 48 days postautograft, respectively. Regenerating marrow cells were 100% Ph- in 13 patients and 75% to 94% Ph- in 3. Between 4 and 36 months (median 12) postautograft, Ph+ cells became detectable in all but 1 (who died in remission) of the 13 patients who achieved complete cytogenetic remission. Four of 7 evaluable patients treated with low-dose interferon alpha were returned to complete cytogenetic remission. Thirteen group 1 patients (81%) are alive 1.0 to 5.7 years (median 2.6) after autografting: 4 in complete cytogenetic remission, 2 in hematologic remission, 6 in chronic phase, and 1 in myeloid blast phase. Three group 2 patients (50%) are alive at 2.6, 3.8, and 4.3 years after autografting: 1 in partial cytogenetic remission, 1 in chronic phase, and 1 in accelerated phase. Thus, autografts of cultured marrow can result in prolonged restoration of Ph- hematopoiesis for some patients with CML.
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PMID:Autografting with cultured marrow in chronic myeloid leukemia: results of a pilot study. 804 56

Since early eighties there have been several studies evaluating the effectiveness of biotherapy with natural and recombinant interferon alpha (IFN-alpha) in patients with proliferative hemocytopathies of both lymphoid and myeloid origin. In patients with hairy cell leukemia (HCL) interferon induces clinical and hematological remission and was considered for several years as the treatment of choice in the management of this disease. Subsequently it was found that IFN reveals myelosuppressive effect in patients with chronic myelogenous leukemia (CML) leading in majority of them to clinical and hematological remission and in part--cytogenetic one. Interferon decreases also thrombocytosis and its thrombotic-haemorrhagic complications in patients with essential thrombocythemia (ET) and decreases erythrocyte count in patients with polycythemia rubra vera (PRV).
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PMID:[Use of interferon in patients with hairy cell leukemia and myeloproliferative disorders]. 806 97

From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to 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:The German CML study, comparison of busulfan vs. hydroxyurea vs. interferon alpha and establishment of prognostic score 1. 825 90

Fifty-one patients with CML in chronic phase, less than two years after diagnosis, were included in one multicentric study aiming to assess the therapeutic value of interferon alpha 2a (IFN alpha 2a) in this setting. The therapeutic scheme was biphasic: The patients were first treated with hydroxyurea, and afterwards only received IFN alpha 2a, at a planned dose of 5MU/m2/day, s.c. Thirty-eight patients (81%) achieved an hematologic response, which was complete in 57% of the total group. The median time to response was of 42 days. In the last evaluation, a complete hematologic response was sustained in 21 patients (47%). Philadelphia suppression was obtained in 44% of the patients who achieved hematologic responses; major cytogenetic responses were obtained in 16% of the patients. The patients who obtained genetic responses were significantly younger and had a shorter interval from diagnosis to IFN than the patients who did not respond. At the moment of evaluation, 90% of the patients are alive, but the median follow-up of the series (217 days, range 21-1150) is too short to analyze any impact of IFN over survival. Six patients (12%) discontinued IFN because of toxicity, three of them because of severe flu-like syndrome. Leukopenia and thrombocytopenia were frequent, but rarely severe. Hypertriglyceridemia has been a very frequent finding.
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PMID:Interferon alpha 2A in the treatment of chronic myelogenous leukemia in chronic phase. Results of the Spanish Group. 825 92

Thirty patients with chronic myeloid leukemia from 11 Israeli medical centers entered this study. Their ages ranged from 16-65 (median 41) and time from diagnosis to treatment was 1-16 months (median 4 months). After cytoreductive therapy with hydroxyurea (22 patients) or busulphan (8 patients), patients received 9 million units/day of recombinant interferon alpha-2 alpha (Roferon A) subcutaneously. Side effects included arthralgia or low back pain in 7 patients, thrombocytopenia in 9, weight loss in four, neurologic disturbances in 4 and leukopenia in 3 cases. Seventeen patients achieved complete hematologic remission (CHR) and 6 partial hematologic remission (PHR). Six patients achieved major cytogenetic response, 4 of them lost all Ph1 chromosome positive cells and 4 had minimal cytogenetic response. Frequency of relapse was high: 8 patients with CHR and 6 with PHR relapsed, but patients with major cytogenetic response did not relapse. Patients who had received prior therapy with busulphan had a higher remission rate but a lower quality of cytogenetic response. Escalation of Roferon to 12 million units per day in relapsing or nonresponding patients induced PHR in 2/7. Neutralizing anti-interferon antibodies occurred in 7 relapsing or nonresponding patients. The cytoreductive induction with hydroxyurea enhanced the hematologic remissions to a median of 6 weeks. Further studies should define the role of combination therapy in order to improve response and prevent relapses.
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PMID:Treatment of chronic myeloid leukemia with interferon alpha (Roferon): results of the Israeli Study Group on CML. 825 95

New developments in relation to chronic myelogenous leukemia (CML) are characterized by progress in knowledge of pathogenesis, diagnostic improvement such as nosology of Philadelphia-negative CML and diagnosis of minimal residual disease by molecular techniques, advances in drug therapy with hydroxyurea or interferon alpha, and progress in bone marrow transplantation through availability of unrelated donors. In addition, the recognition of suitable prognostic parameters indicates that risk adapted therapy may become possible.
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PMID:[Chronic myeloid leukemia. State of the art, May 1993]. 829 89


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