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 medical records of 77 patients with hematologic malignancy who were admitted to a medical intensive care unit over a 21-month period were reviewed. The overall hospital mortality rate was 80 percent. Sixteen patients (21 percent) were discharged from the intensive care unit but eventually died in the hospital. The cause of death was the result of a new problem in only three of these 16 patients. Hypotension (shock) and acute respiratory failure were the reasons prompting admission to the intensive care unit in 75 percent, but death in the intensive care unit was almost always the result of intractable hypotension rather than refractory hypoxemia. Only four of 52 patients who required mechanical ventilation left the hospital. In all four, the duration of ventilatory support was less than five days and the cause of respiratory failure was noninfectious in nature. Factors such as congestive heart failure, leukopenia, and abnormalities in mental status modified the hospital course, but did not alter outcome once prolonged mechanical ventilation became necessary. The data suggest that once acute respiratory failure develops in patients with lymphoma or leukemia, presumably as a result of infection, and mechanical ventilation for more than a relatively brief period is required, the prognosis is uniformly grim. Decisions to limit aggressive therapies is subsets of intensive care patients such as these should be aided by data that show a lack of precedent for meaningful recovery.
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PMID:Precedents for meaningful recovery during treatment in a medical intensive care unit. Outcome in patients with hematologic malignancy. 657 89

Alpha and beta interferon were tested for antitumor activity and clinical toxicity in 15 children suffering from cancer. The drug was administered IV, IM, IT or intralesionally daily in the majority of cases in total doses of 18 X 10(6) to 9,634 X 10(5) IU. Major toxicities were a flulike syndrome, elevation of transaminase activity and leukopenia. A minor response (less than 50%) was observed in one patient with glioblastoma, treated by intrathecal administration, and an objective local response was noted in one rhabdomyosarcoma patient with multiple subcutaneous metastases, who was treated by intralesional administration. CNS leukemia in two patients improved without hematological response. Further trials are warranted.
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PMID:[Clinical experience with alpha and beta interferon in childhood cancer]. 659 60

Twenty-three cases of hematological malignancies (18 plasma cell neoplasm, 2 leukemia and 2 malignant lymphoma) were treated with recombinant human leukocyte interferon (rIFN-alpha A). Among plasma cell neoplasms, excellent and good responses were obtained in 1 case of IgG myeloma and 1 case of Bence-Jones myeloma respectively and fair response was obtained in 5 other cases. Response rats was 11.4%, or 38.9% if fair response was included. Partial remission was obtained in 1 case of chronic lymphocytic leukemia. In one of 2 cases of acute lymphoblastic leukemia, marked reduction of peripheral leukemia cells was noted. Side effects included fever (65%), malaise (20%), nausea-anorexia (43%), leukopenia (52%) and thrombocytopenia (52%). However, all were not serious and disappeared quickly after discontinuation of rIFN-alpha A.
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PMID:[Treatment of hematological malignancies with recombinant leukocyte A interferon (rIFN-alpha A)]. 659 73

A case of hairy-cell leukemia that started with cutaneous lesions similar to those of acute febrile neutrophilic dermatosis (Sweet's syndrome) is reported. The patient had leukopenia and a recurrent eruption for a year prior to the diagnosis of the hematologic disorder. Bone marrow examination eventually demonstrated characteristic "hairy" cells with tartrate-resistant, acid-phosphatase activity. Biopsy of a cutaneous lesion suggested an abscess showing a dense neutrophilic dermal infiltrate with perivascular predilection. The findings of IgA, IgM, C3, and fibrinogen in vessel walls by immunofluorescence and vascular disruption by electron microscopy contribute additional evidence for an immunologic determinant in this instance of Sweet's syndrome. It is known that neutrophilic infiltrates of Sweet's syndrome may have a variety of clinical presentations. This is the second case of hairy-cell leukemia with which Sweet's syndrome was associated.
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PMID:Acute febrile neutrophilic dermatosis (Sweet's syndrome) in a patient with hairy-cell leukemia. 662 20

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

The clinical effects of 10-deaza-aminopterin, an inhibitor of dihydrofolate reductase with a better therapeutic index against several murine tumors than that of methotrexate, were examined during the course of a phase I study in patients with advanced malignant neoplasms. Three escalating dose schedules were explored: single iv injections once daily, single iv injections twice weekly, and continuous infusion. The maximum tolerated doses were: single injections at a dose of 7 mg/m2/day for 5 days; single injections at a dose of 15 mg/m2 twice weekly for four to six doses; and continuous infusion at a dose of 3 mg/m2/day for 5-6 days in patients with solid tumors and until bone marrow hypoplasia in patients with leukemia. Mucositis was dose-limiting in all schedules. Occasionally, mild leukopenia, thrombocytopenia, and skin rash were noted. A minor antitumor response was seen in a patient with gallbladder carcinoma. Marked leukemic cell kill was observed in several patients with acute leukemia or blastic phase of chronic myelogenous leukemia. Disease-oriented phase II trials are planned at this Center for several tumor varieties.
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PMID:Phase I trial of 10-deaza-aminopterin in patients with advanced cancer. 682 21

To determine the incidence and types of infections in Hodgkin's disease, particularly those related to the overwhelming pneumococcal sepsis syndrome, 210 consecutive patients with previously untreated Hodgkin's disease who underwent staging laparotomy with splenectomy from March 1968 to October 1979 were reviewed. For 178 patients (85 percent) alive at the end of the study, the mean follow-up time was 68.1 months. Eighty-two serious infections occurred among 59 (28 percent) of the patients; 47 (57 percent) serious infections were microbiologically documented and 35 (43 percent) were clinically documented. Forty-seven microbiologically documented serious infections occurred in 34 patients and consisted of 23 episodes of pneumonia, 10 cases of bacteremia, seven wound infections, two cases of disseminated herpes zoster, one subphrenic abscess, and four miscellaneous infections. Microbiologically documented serious infections occurring during initial treatment or remission had lower incidences of leukopenia (29 versus 58 percent) (p = 0.09) and death (11 versus 53 percent) (p = 0.005) than those occurring after relapse of Hodgkin's disease. Of the microbiologically documented serious infections, 76 percent were associated with a predisposing factor(s) (leukopenia, postoperative state, steroids, peripheral neuropathy, leukemia), of which 34 percent were fatal. Microbiologically documented serious infections unassociated with a predisposing factor were never fatal, including the only episode of pneumococcal sepsis in the series. In contrast to microbiologically documented serious infections, only 14 percent of clinically documented serious infections (versus 38 percent) were fatal. The overwhelming pneumococcal sepsis syndrome and other infections thought to be associated with the asplenic state are uncommon problems in patients with Hodgkin's disease after splenectomy.
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PMID:Infection among 210 patients with surgically staged Hodgkin's disease. 685 90

In parallel with an ongoing clinical trial in patients with metastatic mammary carcinoma, we compared the three-drug combination of cyclophosphamide, tegafur, and methotrexate with the two-drug combination of cyclophosphamide and tegafur in the murine L1210 leukemia and B16 melanoma models. The obtained data based on a central composite design were calculated by mathematical models, which estimate optimum dose combinations for survival by restricting side effect constraints (loss of weight, leukopenia). The main results were as follows: (a) long-term survival can be reached only by accepting a relatively high toxicity in each case, and (b) in the L1210 model the three-drug combination was superior to the two-drug combination, while in the B16 melanoma cyclophosphamide as a single agent offered the best results. The experimental yields are in accordance with preliminary results of the clinical trial. The mathematical model used offers the possibility of comparing drug combinations in a relatively economic way.
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PMID:Use of mathematical models for the evaluation of two- and three-drug combination chemotherapy in murine tumor models. 687 80

m-AMSA is a synthetic aminoacridine DNA intercalator found to have experimental murine antitumor activity. A phase I investigation was undertaken in 71 patients with solid tumors and acute leukemia. Using an intermittent every 3-week schedule in solid tumors, toxicity encountered was primarily hematologic, predominantly leukopenia with relative platelet sparing. The recommended dose for phase II evaluation in patients with solid tumors is 90 mg/m2 every 3 weeks; patients with minimal prior therapy could be treated at 120 mg/m2 and patients with hepatic dysfunction or marginal bone marrow reserve should have an initial dose reduction to 70 mg/m2. Therapeutic activity was seen in Hodgkin's disease, hepatoma, and epidermoid carcinoma of the esophagus. Various dose schedules were studied in leukemia. The recommended dose for phase II evaluation is 120 mg/m2 daily for 5 days as a daily 30-minute infusion. At this dose, nausea, vomiting, mucositis, alopecia, and hepatic toxicity were noted. Therapeutic activity was seen in AML, blastic CML, and CLL. Further clinical trials with this agent are warranted.
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PMID:Phase I study of m-AMSA in patients with solid tumors and leukemias. 689 83

Forty-six patients with inoperable cancer and leukemia in relapse were given vindesine (VDS) either by iv bolus weekly at doses ranging from 2.0 to 5.5 mg/m2 or by 24-hour continuous infusion weekly at doses ranging from 1.0 to 7.0 mg/m2 of estimated body surface area. VDS was well-tolerated by patients with normal liver function who had previously been minimally treated with myelosuppressive agents at a dose of less than or equal to 4 mg/m2 either by iv bolus or by 24-hour infusion weekly. The dose-limiting toxic effects of VDS were leukopenia and neurotoxicity. Leukopenia was cumulative but easily reversible by interruption of weekly dose. Neurotoxicity was insidious and hardly reversible. Patients with liver dysfunction appeared to develop more neurotoxicity. Other toxic effects included a decrease in hemoglobin level, transient hepatic dysfunction, cellulitis or phlebitis at the iv site, stomatitis, nausea, and vomiting. Degrees and parameters of toxic effects observed after iv bolus and 24-hour infusion of the same doses were indistinguishable except for an increased incidence of local cellulitis in the infusion group.
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PMID:Initial clinical study with vindesine: tolerance to weekly iv bolus and 24-hour infusion. 692 28


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