Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety nine patients with leukemia and/or related disorders were treated with cefmenoxime (CMX). Among them, 77 patients had severe infections, while other 22 patients did not suffer from infection, but it was expected that they would fall into serious conditions if they were infected. Sixty of the 77 patients who had severe infection were used in the evaluation of effectiveness. The remaining 17 patients were not evaluated because they were subjected to combined treatments of CMX and other therapeutic agents such as other antibiotics, gamma-globulin or interferon. Excellent responses were found in 26 (43.3%) patients and good responses in 12 (20.0%) patients. In total, the rate of effectiveness was 63.3%. Nineteen of the 22 patients who were treated prophylactically with CMX were used in the evaluation of effectiveness, while 3 patients were excluded from the evaluation because peripheral neutrophils were counted to be more than 1,000/mm3 before CMX was administrated, although these 3 patients were used in the final evaluation to examine side effects. In the prophylactic treatment, the rate of effectiveness was 89.5%. The side effects were seen in 4 patients (4/82:4.9%). A different symptom was identified in each patient. These symptoms were skin rash, mild nausea, mild diarrhea and slight elevation of serum bilirubin. Prompt improvements of these symptoms occurred as soon as CMX administration was stopped. These results show that CMX is a therapeutically effective and safe antibiotics for the treatment of severe infections or for the prophylaxis of infections in patients associated with leukemia and/or related disorders.
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PMID:[Clinical evaluation of cefmenoxime in severe infections in leukemia and related disorders]. 346 72

We conducted a phase I and pharmacokinetic study of i.v. idarubicin, a new anthracycline analogue, in 42 evaluable children 1-19 years old. Twenty-seven had leukemia and 15 had various solid tumors. The drug was administered in escalating doses of 10 to 40 mg/m2/course in 3 equal fractions over 3 consecutive days at 14- to 21-day intervals. Myelosuppression and mucositis were the limiting toxicities for short-term administration. Nausea, vomiting, and elevation of liver enzymes and bilirubin were the other toxicities encountered. Peak toxicity occurred 2 weeks after drug administration with median recovery by day 24. All but 4 patients with solid tumors had prior anthracyclines. Mild cardiac function changes without clinical symptoms were observed in 17 of 35 patients measured by serial cardiac evaluations. In addition, there were 4 patients with congestive heart failure. On postmortem examination, 4 patients had changes consistent with anthracycline cardiomyopathy at a prior median total anthracycline dose of 175 mg/m2. The maximum tolerated dose for patients with solid tumors was 15 mg/m2 course in 3 divided doses. Patients with leukemia tolerated 30 mg/m2/course. Six of 15 evaluable patients with acute lymphoblastic leukemia who received greater than or equal to 30 mg/m2 idarubicin achieved a remission (M1 marrow status). The plasma clearance of idarubicin fits a 3-compartment model with a harmonic mean half-life of 2.4 min, 0.6 h, and 11.3 h for alpha, beta, and gamma phases, respectively. Idarubicinol was the only metabolite detected in the plasma and it accumulated during the 3 days of therapy. Idarubicin is similar to daunorubicin in pharmacology and toxicity. While the cardiotoxic dose still must be delineated, the complete remission achieved in multiple relapsed patients with acute lymphoblastic leukemia indicate promising activity in at least that disease.
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PMID:Phase I and clinical pharmacological study of 4-demethoxydaunorubicin (idarubicin) in children with advanced cancer. 347 21

Aclarubicin is a new anthracycline antibiotic that produces substantially less cardiotoxicity in animals that does doxorubicin. Based upon prior Phase I and II trials in leukemia, a Phase II study in acute myeloblastic leukemia was developed to assess the response rate and toxicity in previously treated patients. Forty patients received aclarubicin 100 mg/m2 per day X 3 with repeated course on days 14-16 if marrow hypoplasia was not produced. Complete responses were achieved in 27.5% (11/40) with durations of 1.5, 2, 2, 2, 3, 3+, 4, 5+, 32+, 33+, and 34+ months. Toxic effects of this therapy included severe neutropenia and thrombocytopenia, nausea/vomiting, mucositis, and diarrhea. No patient developed significant changes in the left ventricular ejection fraction, as measured by radionuclide angiography, or any clinical cardiac symptoms. Alopecia was minimal. Aclarubicin can produce a significant response rate in previously treated patients with acute myeloblastic leukemia and should be considered for study in initial therapy.
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PMID:Phase II study of aclarubicin in acute myeloblastic leukemia. 347 91

Forty-six patients with acute leukemia were treated with mitoxantrone as a single agent. Twenty-nine patients had relapsed and/or refractory acute leukemia. Seventeen patients with acute non-lymphatic leukemia had received no prior treatment. Twelve mg/m2 of mitoxantrone was given intravenous on five consecutive days. Treatment related side effects included bone marrow suppression, mucositis, alopecia, nausea, vomiting and infection. Cardiotoxicity was documented in 7 patients. This study reconfirms that mitoxantrone is an active agent in acute leukemia with complete response documented in 10 of 29 patients with relapsed and/or refractory acute leukemia (34% response rate, 95% confidence limits 18-53%) and complete response documented in 11 of 17 patients (65% response rate, 95% confidence limits 38-87%) with previously untreated acute nonlymphatic leukemia.
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PMID:Mitoxantrone in the treatment of acute leukemia. 348 64

Eight patients with hairy-cell leukaemia (HCL) complicated by pancytopenia were treated with low dose regimens of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (DCF). All patients had significant haematological and clinical improvement. One patient who had been splenectomized and five patients with mild to moderate splenomegaly achieved normal blood counts within 2 months, which have been maintained for up to 18 months. Complete remissions occurred in two patients and four patients had 50-95% marrow clearance of hairy cells. The initial DCF treatments produced a 1-3 g/dl fall in the haemoglobin levels and one patient had a temporary reduction in granulocyte and platelet counts. Five patients had nausea/vomiting, and/or lethargy following DCF, but there was no correlation between the plasma levels of deoxyadenosine and adenosine and the incidence or severity of these side effects. An increased incidence of infection and drug hypersensitivity may reflect the effects of DCF on the immune system. Low dose DCF is a highly effective agent in HCL.
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PMID:The treatment of hairy-cell leukaemia with 2'-deoxycoformycin. 348 71

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.
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PMID:A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia. 354 13

A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg-1 which was escalated up to 24 mg kg-1. Major side effects were nausea, vomiting and anorexia, and mild myelosuppression was noted at 12 mg kg-1 or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg-1 or more and became frequent at 7 mg kg-1 or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg-1 or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg-1 day-1 of PLAC.
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PMID:Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine. 366 79

Mitoxantrone was evaluated in a multi-institution trial to define the effective dose for treating acute leukemia, to evaluate its toxicity, and to assess the induction rates for the different types of acute leukemia. Fifty-seven patients have been treated. Of the 24 patients receiving mitoxantrone (10 mg/m2/day X 5), one of nine with acute nonlymphoblastic leukemia (ANLL) in relapse, one of five with acute lymphoblastic leukemia in relapse, and one of seven with blastic chronic myelogenous leukemia achieved remission. At a dose of 12 mg/m2/day X 5, seven of 16 patients with ANLL in relapse, none of six with acute lymphoblastic leukemia in relapse, and one of five with blastic chronic myelogenous leukemia achieved remission. At both dose levels, there was no response in patients who had failed to achieve a prior remission. Toxic effects included nausea/vomiting, stomatitis, and hepatic dysfunction. Nine of the 57 patients treated experienced cardiac events but cardiac toxicity seemed clinically significant in only three. We conclude that mitoxantrone, at a dose of 12 mg/m2/day X 5, is effective therapy for ANLL. Trials combining mitoxantrone with other agents are needed.
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PMID:Phase I-II trial of mitoxantrone in acute leukemia. 385 86

A 41-year-old male was diagnosed as acute lymphocytic leukemia (ALL) in November, 1982 and partial remission was obtained by a combination chemotherapy of LVP, DVP ABOP and VAMP. In January, 1983, peripheral blood showed an increasing number of leukemic cells and he was readmitted to our hospital. WBC count in the peripheral blood was 13,200/mm3 and an 82% ratio of leukemic cells was observed. Bone marrow aspiration showed a hypercellularity of 89.4% leukemic cells. High-dose Ara-C therapy was started at a dose of 3 g/m2 i.v. every 12 hours for 6 days. Leukemic cells in peripheral blood were rapidly decreased in number, and the nucleated cell count of bone marrow was also reduced after 3 weeks of treatment, however 95% of leukemic cells remained. Low-dose L-asparaginase was then supplemented at a dose of 2000 U for 3 days, and 2 months later complete remission was achieved. The side effects associated with this high-dose Ara-C therapy were nausea, vomiting, diarrhea, fever and conjunctivitis, although these were tolerable. These observations suggest that high-dose Ara-C combined with L-asparaginase should be added to the treatment of leukemia which is refractory to conventional chemotherapy.
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PMID:[Complete remission obtained in refractory acute lymphocytic leukemia using high-dose cytosine arabinoside combined with low-dose L-asparaginase]. 385 16

Successful treatment of CNS leukemic relapse has been frustrated by frequent local recurrence and eventual marrow relapse. We describe the treatment of meningeal leukemia in 39 children with intrathecal remission induction followed by the placement of an Ommaya reservoir to facilitate the administration and distribution of chemotherapeutic agents into the CSF. Six hundred or 900 rad of craniospinal radiation and maintenance intraventricular and intrathecal chemotherapy was then administered. Systemic reinduction therapy was added in the later cases. Sixteen children (41%) experienced no further events, with 17+ months to 13+ years (median, 25 months) follow-up . Eleven patients (28%) had CNS recurrence, nine (23%) bone marrow (BM) relapse, and two (5%) testicular relapse as the next adverse event. The course of patients with first isolated CNS relapse differed from that of the others. Eleven (69%) of 16 patients treated for first isolated CNS relapse are alive and 9 are event free, while only 35% of patients whose CNS relapse occurred simultaneously or after recurrent disease at other sites are alive (P = .04). Seven of 23 in the later group are event free. The difference is due to the increased incidence of BM relapse in the later group (30% v 6%; P = .04). For patients with first isolated CNS relapse, the life-table median CNS remission duration is 42 months. The projected CNS relapse-free survival and event-free survival 8 to 10 years after CNS relapse are 40% and 32%, respectively. Headache, nausea, and emesis of short duration were frequent during therapy. In three patients, the reservoir had to be removed for infection. No patient suffered neurologic deficit related to the reservoir. The therapy described can reduce the CNS relapse rate with manageable toxicity. Systemic relapse is still a major problem after multiple CNS relapse and in those in whom the CNS relapse follows or is simultaneous with relapse at other sites.
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PMID:Therapy of CNS leukemia with intraventricular chemotherapy and low-dose neuraxis radiotherapy. 386 74


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