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

Twenty-six patients with acute leukemia in relapse were treated with mitoxantrone (dihydroxyanthracenedione dihydrochloride). The drug was given as a rapid i.v. infusion for 5 days, and doses were escalated from 8 mg/sq m daily for 5 days to 20 mg/sq m daily for 5 days. Five of 12 patients with acute lymphoblastic leukemia were induced into complete remission; one patient was induced into complete remission twice. The marrow response lasted from 3 to 50+ weeks. Among 12 patients with acute myelogenous leukemia, there was one complete and one partial remission, with response duration lasting 8 and 2 weeks. One patient with chronic myelogenous leukemia in blastic crisis also had a partial remission lasting 17 weeks. Remissions occurred at doses ranging from 8 to 14 mg/sq m daily for 5 days. All responders had been treated previously with anthracyclines. Drug-induced side effects included dose-limiting oral mucositis, sporadic nausea and vomiting, and transient elevations of the hepatic enzymes. Approximately one-third of the patients had septic complications during the myelosuppressive phase following treatment. We believe that mitoxantrone has definite utility in the treatment of acute leukemia in relapse.
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PMID:Mitoxantrone in patients with acute leukemia in relapse. 686 Nov 54

Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.
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PMID:Treatment of acute leukemia in relapse with 4'(9-acridinylamino) methanesulfon-m-anisidide (AMSA) in combination with cytosine arabinoside and thioguanine. 689 90

Thirty-two patients with relapsed or resistant acute leukaemia were treated with m-AMSA at doses ranging from 50-150 mg/m2 daily for 5 days. Complete remission was achieved in three of 18 patients with acute myeloblastic leukaemia, two of nine patients with acute lymphoblastic leukaemia, and none of five patients with blastic crisis of chronic myeloid leukaemia. The complete remissions all occurred at doses of 100 mg/m2 per day or above. Haematological toxicity occurred in all patients and was dose-related. Nausea and vomiting were mild and easily controlled. Alopecia was uncommon at the lower doses but occurred in all patients receiving the higher doses. Stomatitis was noted in only 8% of courses at 50 mg/m2 but was seen in 50% of courses at 150 mg/m2. Mild and transient elevations of liver enzymes were common. m-AMSA is an active drug in acute leukaemia, with acceptable toxicity. Its place in combination chemotherapy is now being explored.
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PMID:A phase I and II study of m-AMSA in acute leukaemia. 694 78

AMSA was evaluated in the treatment of 109 adults with previously treated acute leukemia. Of the 102 evaluable patients, 82 had AML, 17 ALL, and 3 CML in blastic phase. A number of different dose schedules of AMSA were explored, and we conclude that the optimum dose of AMSA for remission induction in acute leukemia is 120 mg/sq m/day for 5 days. Complete remissions were observed in 23 (28%) patients with AML and in 1 patient with ALL. Patients who achieved complete remission were maintained on AMSA using a dose of 30-40 mg/sq m/day for 5 days repeated at 4-wk intervals. The median duration of complete remission was 12 wk (3-59 wk), and the responders survived significantly longer than the failures (27 wk versus 8 wk, p = 0.002). The side effects associated with AMSA therapy included mild nausea and vomiting, stomatitis, diarrhea, phlebitis, alopecia, and myelosuppression-related infections. Our results indicate that AMSA is a useful new antileukemic agent for the treatment of relapsed acute leukemia and appears to have activity comparable to that of the currently available drugs, such as cytarabine and the anthracycline antibiotics.
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PMID:Evaluation of AMSA in previously treated patients with acute leukemia: results of therapy in 109 adults. 695 87

In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.
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PMID:High dose cyclophosphamide: stem cell mobilizing capacity in 21 patients. 792 Feb 30

Current anti-leukemic chemotherapy in patients with myelodysplastic syndromes (MDS) and MDS evolving to acute myeloid leukemia (AML) is associated with low response rates and high treatment-related toxicity. Homoharringtonine (HHT) is a novel cephalotaxime alkaloid with reported efficacy in relapsed and de novo AML and more recently, chronic myeloid leukemia. Although its mechanism(s) of action is not completely understood, in vitro studies have demonstrated both cytotoxic and differentiating activity in leukemic cells, as well as intra-cellular changes suggestive of apoptotic cell death. In a phase II trial, HHT was administered at a dose od 5 mg/m2 by 24-h continuous infusion daily for 9 days to patients with MDS and MDS evolving to AML (MDS/AML). Twenty-eight patients (MDS 16, MDS/AML 12) with a median age of 67 years (range 23-83) were entered. A complete remission was achieved in seven patients, a partial remission was achieved in one patient for an overall response rate of 28% (8/28). There were four of 13 responders in MDS/AML patients and four of 15 in patients with MDS. The median duration of complete response was 7 months (range 2-10). Significant myelosuppression was universal and resulted in a high incidence of induction deaths (13/28) due to neutropenic-related infections. Extramedullary toxicity was mild and consisted of hypo-tension, fluid retention, hypoglycemia, diarrhea, nausea and vomiting. HHT given in this dose and schedule demonstrated limited activity in MDS and MDS/AML and was associated with prolonged pancytopenia and marrow hypoplasia in many patients. Administration of HHT at a lower dose or in combination with hematopoietic growth factors may lead to better results, but treatment with HHT as single agent at this dose and schedule is not currently recommended for these patients.
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PMID:Homoharringtonine in patients with myelodysplastic syndrome (MDS) and MDS evolving to acute myeloid leukemia. 855 35

Fourteen patients with high-risk leukemia (six with relapsed AML, three with relapsed ALL, one with AML-M0, four with CML in myeloid blastic crisis) were treated with a combination chemotherapy of carboplatin (200-300 mg/m2/day) and cytosine arabinoside (100 mg/m2/day) by 24 h continuous infusion for 5-7 days. Five patients (35.7%) achieved complete remission including two patients complicated with myelofibrosis (one with AML-M0 and one with CML in myelo-megakaryocytic crisis). Thirteen patients had nausea and vomiting, five patients had severe, prolonged neutropenia for which it was necessary to administer granulocyte colony-stimulating factor and six patients had severe thrombocytopenia. We concluded that this regimen is effective for the treatment of high-risk leukemia.
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PMID:Combination chemotherapy of carboplatin and cytosine arabinoside for high-risk leukemia: a pilot study. 863 58

The purpose of the study was to define the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of CI-973 a new platinum analogue, in patients with refractory or relapsed acute leukemia. CI-973 was given as a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 150 mg/m2 to 1350 mg/m2 per course. Thirty-six patients were treated including 18 patients with acute myelogenous leukemia (AML), four with acute lymphocytic leukemia (ALL) and 14 with chronic myelogenous leukemia in blastic phase (CML-BP). Severe gastrointestinal and renal side-effects were the dose-limiting toxicities occurring in four of five patients treated with CI-973 1200 to 1350 mg/m2 per course. At the MTD of 1000 mg/m2 per course, three of 13 patients treated (23%) had moderate to severe nausea and vomiting, three (23%) had moderate diarrhea and one had moderate mucositis. Among 21 patients treated at > or = 1000 mg/m2 (15 AML, 6 CML-BP) no objective complete or partial responses were observed. Twelve of 18 patients (66%) with evaluable marrows on day 14 showed significant suppression of marrow blasts percentage and marrow leukemic infiltrate percentage. Tests for measurement of DNA adduct formation in leukemic cells in vivo after CI-973 therapy, and in vitro following exposure of leukemic cells to CI-973 were developed. This study defined the MTD of CI-973 to be 1000 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Gastrointestinal and renal side-effects were dose-limiting. No objective responses were noted in this heavily resistant population. Correlations between CI-973-induced DNA adduct formation and individual patient response to CI-973 will help to define its role in leukemia subsets.
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PMID:Evaluation of CI-973, a platinum analogue, in refractory or relapsed acute leukemia. 864 53

In vitro studies suggest that nucleoside analogs have an antileukemic effect against chronic myelogenous leukemia (CML). We investigated the antileukemia effect of deoxycoformycin (DCF) and fludarabine in patients with CML. Four patients with Philadelphia chromosome (Ph)-positive CML were treated with DCF at 4 mg/m2 every week for 4 weeks, then every other week for four doses, and then every month as maintenance. Two patients were in late chronic phase and two in accelerated phase. All had previously failed therapy with interferon-alpha (IFN-A). Nine patients were treated with fludarabine 30 mg/m2/day for 5 days every 28 days. Three had Ph-positive CML, and six Ph-negative disease. Five patients were in accelerated phase and four in late chronic phase. Three patients treated with DCF had normalization of WBC counts while on the weekly schedule but progressed when changed to every other week. The fourth patient had no objective response. There were no cytogenetic responses. DCF was well tolerated with only mild nausea and vomiting in all patients. Patients treated with fludarabine received a median of two courses (range 1-4). In two patients (both Ph-positive), disease progressed to blastic phase upon recovery. Two other patients died of hemorrhagic complications secondary to thrombocytopenia. In all other cases fludarabine produced a transient reduction of WBC counts, but counts recovered to levels equal to or greater than the pre-treatment values. There were no cytogenetic responses. These results, together with previous experience with 2-CDA producing only hematologic responses, suggest that nucleoside analogs may not have a significant role in the management of CML.
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PMID:Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine. 917 28

Treatment of chronic myeloid leukaemia (CML) with IFN-alpha (IFN) is known to confer significant survival benefit, but the drug's impact on quality of life (QoL) in CML is unclear. We describe a cross-sectional comparison of QoL in patients randomised to long-term treatment with IFN versus no IFN within the UK MRC CML 3 trial, assessing the long-term consequences and psychosocial side effects of IFN therapy. Patients completed the EORTC QoL QLQ-C30, an in-house leukaemia/IFN questionnaire, a brief assessment of sexual functioning and demographic details. In total, 163 eligible patients completed questionnaires (85% response). Patients receiving IFN reported significantly worse QoL for emotional, cognitive and social functioning, pain and dyspnoea (P<0.01), and marginally worse fatigue, nausea and vomiting (P<0.05). As expected from other IFN use, those on IFN experienced more flu-like and febrile symptoms and skin problems than those not on IFN. In all, 35% of patients stopped IFN before questionnaire completion. This made no material difference to the results, except that those continuing on IFN had slightly better self-assessed Global health/QoL than those who had stopped (P<0.03). IFN treatment adversely affected sexual health after allowing for age and gender. In conclusion, IFN treatment has a significant adverse impact on QoL. Patient awareness of the survival benefits and these QoL effects should enable better-informed decision-making. The impact on QoL of IFN dose, and of imatinib therapy versus IFN in early CP CML, are being investigated. QoL will need evaluating in future studies of combination treatment (IFN+imatinib).
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PMID:Treatment of CML using IFN-alpha: impact on quality of life. 1287 50


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