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)

The toxicity of high dose cytosine arabinoside (Ara-C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated. The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitt's lymphoma. Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes. All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia. Adverse reactions were mild and reversible in all patients. No serious neurologic toxicity was seen. The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients. The only life-threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy. While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara-C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis. Side effects of high dose Ara-C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors.
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PMID:Toxicity of high dose Ara-C in children and adolescents. 359 53

Tricyclic nucleoside phosphate (TCN-P) was selected for clinical trials because of its unusual chemical structure and activity against L1210 murine leukemia and MX-1 mammary xenograft. Inhibiting DNA synthesis, TCN-P was more toxic during S-phase of cell cycle. A phase I study was conducted in 24 patients with advanced solid cancers. The drug was given as a slow i.v. injection over 5 min on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 12 to 96 mg/m2 were studied with 3 to 12 patients treated at each level; a total of 106 doses was administered. The major hematological toxicity was thrombocytopenia, with a median nadir occurring at Day 34 of the cycle and first appearing at doses greater than 24 mg/m2. Anemia was seen at each dose level occurring between Days 8 and 34. Non-myelosuppressive toxic effects included stomatitis, anorexia, transient fever, nausea and vomiting, and dose-limiting hyperglycemia and diarrhea. The highest tolerated dose was 48 mg/m2. Plasma, pleural fluid, urine, and tissue samples were analyzed for TCN-P and tricyclic nucleoside (TCN) in selected patients by high-performance liquid chromatography. Plasma decay curves revealed extended retention of both TCN and TCN-P. Autopsy specimens obtained 61 days after therapy showed the highest residues of TCN-P in liver metastases and of TCN in gall bladder, bile, and pancreas. No drug was detected in urine samples of two patients. Prolonged retention and erratic plasma levels of the drug are probably due to extensive enterohepatic circulation, as well as repeated interconversion between TCN-P and TCN within cells. This weekly schedule produced unexpected clinical toxicity and should not be pursued.
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PMID:Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5'-phosphate using a weekly intravenous regimen. 369 29

Seventeen children and two adolescents, aged 6 months to 20 9/12 years, with poor risk leukemia were treated with a total of 38 sequential high-dose ARA-C-Asparaginase courses (HIDAC-ASNase). Each course was followed by profound myelosuppression. Fever occurred in 13.2% and infectious complications in 7.9% of courses. Other side effects were vomiting (81.6%), drug fever (55.3%), mucositis and diarrhoea (28.9%), mild hepatotoxicity (26.3%), exanthemas (18.4%), conjunctivitis (15.8%), local ASNase hypersensitivity (7.9%), athropathy (5.3%). One patient developed generalized seizures followed by coma and death. The possible association between ARA-C, the CNS symptoms and death could neither be demonstrated nor excluded. Except for the possible ARA-C related CNS toxicity, toxic effects were reversible. We consider this treatment a tolerable chemotherapeutic contribution in childhood.
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PMID:Toxicity of sequential high-dose ARA-C asparaginase treatment in childhood poor risk leukemia. 375 57

27 patients (aged 15-55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2 q 12 h X 12) and 3 d of m-AMSA (20 patients), 90-115 mg/m2 daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1-2 courses comprising 4 d of AraC (3 g/m2 q 12 h X 8) and m-AMSA (90-115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction. In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16-25 d (median 21 d) after the remission induction and 14-21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and greater than 9 months (4+ - 16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.
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PMID:Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma. 385 71

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

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.
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PMID:Aclarubicin (aclacinomycin A) in the treatment of relapsing acute leukaemias. 386 84

Clinical effects of sequential administration of high-dose cytosine arabinoside with L-asparaginase were studied in 5 cases of refractory acute leukemia and 2 cases of non-Hodgkin's lymphoma. A total 12 courses were carried out on these 7 patients and complete remission was obtained in 2 courses and partial remission in 3 courses. Two cases of lymphoma with pleural effusion or CNS invasion achieved partial and complete remission, respectively. The side effects associated with this sequential therapy were nausea, vomiting, diarrhea, fever and conjunctivitis, although these were tolerable. These observations suggest that high-dose cytosine arabinoside combined with L-asparaginase is a useful regimen for refractory leukemia and lymphoma.
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PMID:[Sequential combination of high-dose cytosine arabinoside and L-asparaginase in the treatment of refractory acute leukemia and malignant lymphoma]. 386 96

High dose Cytarabin in relapsed and refractory acute leukaemia. High dose cytarabin can be very effective for the treatment of acute leukaemia resistent to conventional cytarabin doses. Therefore 10 patients (6 males, 4 females) with ages ranging from 18 to 58 years (median: 34 years) refractory to conventional induction therapy were treated with 1 hour infusions of high dose cytarabin (3 g/m2 q 12 h for 6 days) 2 patients got additional 20 mg/m2 doxorubicin on days 7 to 9. According to this treatment, in 5 of the 10 patients complete remissions could be achieved. Without further treatment 3 patients relapsed after 4, 7 and 15 months leading to death in 2 or 3 months. 19 months after treatment 1 patient is in complete remission, though demonstrating meningosis leukaemica 5 months after high dose cytarabin. Another patient relapsed 14 months after high dose cytarabin, reaching another complete remission after treatment according to a ALL/AUL protocol [7]. 2 patients died in bone marrow aplasia and 2 patients did not show any response, dying 11 months after high dose cytarabin application. All patients demonstrated vomiting, nausea, diarrhea and allopecia. Bone marrow was profoundly depressed in all patients with severe granulocytopenia and thrombocytopenia for periods from 7 to 34 days. 3 to 5 days after the end of high dose cytarabin therapy 3 patients developed acute ceratitis and 2 patients conjunctivitis. 3 patients showed erythrodermia of their skin with epidermolysis in 2 of these patients.
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PMID:[High-dose cytarabine treatment: a promising therapy modality in acute resistant myeloid leukemias in recurrence]. 388 15

Homoharringtonine (HHT) is a new plant alkaloid originally isolated in the People's Republic of China. Preliminary studies have suggested antitumor activity in several neoplastic diseases. We treated 49 patients with relapsed or resistant acute leukemia with escalating doses of homoharringtonine administered by continuous infusion. Three dose levels were examined: 5 mg/m2 for seven days, 7 mg/m2 for seven days, and 5 mg/m2 for nine days. Of 28 patients with acute nonlymphoblastic leukemia who received cumulative doses of 45 to 49 mg/m2, seven patients (25%) achieved complete remission. Four of these remissions occurred in a subset of ten patients previously resistant to two or more induction attempts with conventional chemotherapy. There were no remissions in three patients with secondary leukemia or in seven patients with acute lymphoblastic leukemia. Reversible hypotension, fluid retention, diarrhea, and tumor lysis syndrome were the major toxic effects of this treatment. Our results indicate that homoharringtonine is an effective new drug for the treatment of acute nonlymphoblastic leukemia and that this drug does not share cross-resistance with conventional antileukemic agents. The recommended dose is 5 mg/m2/d administered by continuous infusion for nine days.
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PMID:Homoharringtonine: an effective new drug for remission induction in refractory nonlymphoblastic leukemia. 388 29

A new regimen for prevention of acute graft-versus-host disease (GvHD)--OKT3 (murine monoclonal anti-pan-T antibody), prednisone and methotrexate (OKT3-pred-MTX)--was compared with the Minnesota standard regimen--antithymocyte globulin, prednisone and methotrexate (ATG-pred-MTX)--for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post-transplant. Twenty patients (aged 25 +/- 9 years) had bone-marrow transplantation (BMT) from their HLA-MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3-pred-MTX) on days 8-22 post-transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 +/- 12 years) who received ATG-pred-MTX on days 8-22 post-transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile. Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (means 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3-pred-MTX and in eight of 19 patients who received ATG-pred-MTX (P = 0.06). The incidence of hepatic or gastrointestinal GVHD (greater than or equal to grade 2) was similar in the two groups: 4/20 OKT3-pred-MTX, 6/19 ATG-pred-MTX. Characteristics of post-transplant infections were also similar for the two prophylactic groups. Survival at 1 year post-transplant was 65% for patients who received OKT3 and 44% for patients who received ATG (P = 0.13). The use of OKT3 with prednisone and methotrexate is relatively safe and is associated with a similar incidence of moderate-severe acute GvHD to that experienced in the use of ATG with prednisone and methotrexate.
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PMID:Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation. 389 Sep 26


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