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)

Sinusitis tends to occur in immunodeficient and immunosuppressed patients during periods of severe leukopenia. This group of patients includes those with primary immunodeficiency diseases, patients with leukemia receiving chemotherapy, and those undergoing bone marrow transplantation or kidney transplantation. The clinical and radiographic signs may be minimal or initially unimpressive. Sinusitis due to Aspergillus, Phycomycetes, or Pseudomonas may be fulminant and even fatal, requiring extensive surgical procedures for control.
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PMID:Sinusitis in immunodeficient and immunosuppressed patients. 388 Aug 49

A Phase II study of recombinant leukocyte A interferon (rIFN-alpha A, Ro 22-8181) was performed in 121 patients with hematological malignancies at 33 institutions from July, 1982 to May, 1984. Patients received Ro 22-8181 by intramuscular injection daily for more than 4 weeks. Daily doses were escalated from 3 X 10(6) to 6X, 9X, 18X, 36X and 50X 10(6) units every 3-7 days. Among 70 evaluable cases, complete or partial responses were observed in 15 patients (21.4%). One complete and 10 partial responses (22.4%) were noted in 49 cases of multiple myeloma, 2 partial remissions (18.2%) in 11 cases of malignant lymphoma and 2 partial remissions (25.0%) in 8 cases of leukemia. Side effects included fever (57.0%), anorexia (34.2%), nausea-vomiting (22.8%), malaise (19.0%), leukopenia (44.3%), thrombocytopenia (45.6%) and increase of GOT or GPT (26.6% or 22.8%). They were all not serious and disappeared quickly after the discontinuation of Ro 22-8181.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in hematological malignancies]. 388 64

Among 31 consecutive patients who developed acute nonlymphocytic leukemia following treatment with chemotherapy or radiation therapy, 17 were treated with intensive chemotherapy aimed at inducing a complete remission. Seven of these 17 patients (41%) obtained a complete remission that ranged in duration from 2 to 11 (median 3) months. Two additional patients who failed to develop normal peripheral blood counts despite postinduction bone marrows that were normocellular and free of leukemia were classified as nonresponders. The median time to complete remission and median duration of leukopenia (WBC less than 1,000/mu 1) were 34 days and 23 days, respectively. Induction chemotherapy was complicated by fever in all patients, documented infection in six patients, and death secondary to sepsis in three. Survival of the 17 patients ranged from less than 1 to 39 (median 4) months. Patients achieving a complete remission had a median survival time of 10 months compared to 2 months for the nonresponders. The other 14 patients received only supportive care and had a median survival of 2 months. These findings indicate that therapy-associated acute nonlymphocytic leukemia (t-ANLL) can frequently respond to chemotherapy and that achieving a complete remission is associated with longer survival. Although these results are encouraging, patients with t-ANLL still have a relatively poor prognosis and efforts directed at improving treatment outcome need to be continued.
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PMID:Response of therapy-associated acute nonlymphocytic leukemia to intensive induction chemotherapy. 401 Jun 22

Fanconi's anemia is a rare genetic disorder associated with congenital deformities, infections, chromosomal abnormalities, and leukemia. This brief article describes the case of a 20 year old man affected with the disease, who was given 100 mg daily of oxymetholone to cure leukopenia and thrombocytopenia. 10 months later he died of hepatic failure. Autopsy revealed hepatoma and liver peliosis, a rare condition of unknown etiology characterized by blood-filled cysts in the liver. It is possible that in the case reported here the hepatoma could have been related to the oxymetholone treatment, which conceivably could have initiated hepatic damage.
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PMID:Hepatoma and peliosis hepatis developing in a patient with Fanconi's anemia. 432 28

We have shown previously that methotrexate pretreatment of murine leukemia and human colon carcinoma cell cultures results in augmented intracellular accumulation of 5-fluorouracil metabolites. Both of these drugs are commonly used for the treatment of women with breast cancer; thus, sequencing of methotrexate before 5-fluorouracil was evaluated in vitro using a human mammary carcinoma cell line, 47-DN. Intracellular 5-fluorouracil accumulation was maximally increased 4-fold in cultures pretreated with 10 microM methotrexate for 24 hr. This enhancement of 5-fluorouracil metabolism was associated with increased intracellular levels of 5-phosphoribosyl 1-pyrophosphate, resulting from the antipurine effect of methotrexate. Brief exposure to exogenous hypoxanthine at physiological concentrations reversed the biochemical synergism between methotrexate and 5-fluorouracil. Other antimetabolites associated with elevations of 5-phosphoribosyl 1-pyrophosphate enhanced intracellular accumulation of 5-fluorouracil up to 2.5-fold. In cloning assays, 18 hr of methotrexate pretreatment followed by 5-fluorouracil resulted in optimal synergistic cytotoxicity, which could be prevented if high concentrations of leucovorin were given between methotrexate and 5-fluorouracil administration. Since these results indicated that optimal breast tumor toxicity in vitro was achieved by 18- to 24-hr sequencing of methotrexate and 5-fluorouracil, clinical toxicity study was carried out to assess whether this drug schedule could be tolerated. Seven patients with advanced cancer were treated with 21 courses of sequential therapy. No toxicity occurred with 38% of treatment courses; mild to moderate leukopenia and mucositis occurred with 29 and 38% of courses respectively. Toxicity was related to treatment interval and not cumulative drug dose or elevated serum methotrexate levels. These clinical results suggest that Phase II studies evaluating 24-hr-sequenced methotrexate and 5-fluorouracil in breast cancer are warranted.
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PMID:Optimal schedule of methotrexate and 5-fluorouracil in human breast cancer. 617 6

Eight patients with small cell bronchogenic carcinoma treated with intensive combination chemotherapy, with and without radiotherapy, have been followed for a minimum of two and a half years without relapse. One patient, after a prodrome of macrocytic sideroblastic anemia, leukopenia, and thrombocytopenia, experienced erythroleukemia 34 months after starting chemotherapy, and cytogenetic studies revealed extensive chromosomal abnormalities. Another patient had persistent macrocytic anemia and pancytopenia two years after cessation of therapy. The remaining six patients had normal peripheral blood smears and cell counts. A significant incidence of preleukemia syndromes and acute leukemia appearing as late complications in intensively treated small cell lung cancer patients requires confirmation in larger series of long-term survivors. Prospective determination of marrow karyotype abnormalities may help to identify patients at greatest risk for developing secondary leukemia.
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PMID:Erythroleukemia and other hematologic complications of intensive therapy in long-term survivors of small cell lung cancer. 627 4

Twenty patients undergoing allogeneic bone marrow transplantation and 39 patients receiving remission induction chemotherapy for acute leukaemia were entered into a double blind, placebo controlled stratified trial of acyclovir prophylaxis against herpes group virus infections. Within the transplant group intravenous acyclovir 5 mg/kg twice daily given throughout the period of granulocytopenia completely prevented oropharyngeal herpes simplex virus infection compared with a 50% incidence in the placebo arm (p = 0.033). The acyclovir group also had fewer days of fever during the trial and a shorter duration of leukopenia, possibly because of the prevention of herpes simplex virus infections. There was a high incidence of herpes infections after the trial in patients who received either acyclovir or placebo. In the non-transplant group there was also a significant reduction of herpes simplex virus infection in the oropharynx and oesophagus (two out of 19 patients as compared with 10 out of 20; p = 0.018). Herpes simplex virus was isolated in the acyclovir arm within a day after starting the trial in one patient, and the other failure was due to a virus with reduced sensitivity to acyclovir in a patient who had had several previous courses of the drug. The incidence of herpes infections after stopping treatment was low. The influence of acyclovir on excretion of Epstein-Barr virus in saliva in either group was inconclusive. One patient (transplant group) developed a cytomegalovirus infection while receiving acyclovir. Acyclovir provides effective prophylaxis against oropharyngeal and oesophageal herpes simplex virus infection in severely immunocompromised seropositive (greater than or equal to 1/8) patients. In patients given bone marrow transplants this may have the additional benefit of reducing the time to recovery of an adequate blood count and the number of days of fever.
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PMID:Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial. 630 64

4'-epi-doxorubicin (4'-epi-DX) is a new anthracycline antibiotic. It differs from doxorubicin (DX) by the epimerization of the OH group in position 4' of the aminosugar moiety, and was synthesized in an effort to find agents with a superior therapeutic index to the parent compound doxorubicin (DX). 4'-epi-doxorubicin binds to DNA and inhibits nucleic acid synthesis and function. The antitumor activity of 4'-epi-DX in several experimental tumors (Leukemias L 1210, P 388, Gross Leukemia, Sarcoma 180 ascitic and solid, C3H/HE mammary carcinoma) is similar to that of DX. However, 4'-epi-doxorubicin has greater antitumor activity than doxorubicin in Lewis lung carcinoma, MS-2 sarcoma lung metastasis, and human melanoma in athymic mice. In chronic toxicity studies there were no qualitative differences between 4'-epi-DX and DX; quantitatively, however, 4'-epi-DX was less toxic. In different experimental models 4'-epi-DX has been shown to be less cardiotoxic than its parent compound. In chronic toxicity studies in the rabbit, histopathologic findings revealed the same pattern of cardiotoxicity for both drugs but less marked with 4'-epi-DX. Distribution studies in mice with tumors showed a lower concentration of 4'-epi-DX in the heart, spleen and kidneys; the hepatobiliary metabolism and excretion of 4'-epi-DX investigated in the rat, indicated that the new analogue was more extensively metabolized than the parent compound. Pharmacokinetics of 4'-epi-DX in humans showed a multiexponential decrease of plasma levels; the same pattern was observed for the metabolite 13-OH epidoxorubicinol but with lower concentrations than the unchanged drug. A high plasma clearance (0.9-1.41/min), a terminal half-life of about 30-40 hr and a large volume of distribution were the main pharmacokinetic characteristics of 4'-epi-DX. A reduction of the dose appears to be appropriate in patients with liver function impairment. Phase II studies with 4'-epi-DX have indicated that the drug produces a pattern of acute toxicity, including acute cardiac toxicity, qualitatively similar to that of DX at identical doses but quantitatively lower, with particular regard to leukopenia and gastrointestinal toxicity. The range of single active doses is between 60 and 90 mg/m2, the most frequently employed doses schedules being 75 or 90 mg/m2 i.v. every 3 weeks. 4'-epi-DX has shown activity in a variety of tumors such as breast carcinoma, soft tissues sarcomas, NH lymphomas, leukemias, ovarian cancer and gastric cancer. Preliminary evidence of activity has been found in melanoma, rectal cancer and pancreatic cancer suggesting a broad spectrum of activity. As to chronic cardiac toxicity up to now only 2 mild to moderate and reversible CHF have been observed at doses of 1120 and 1235 mg/m2 in about 700 treated patients. Specific and comparative studies are in progress: preliminary findings from a randomized comparison of 4'-epi-DX vs DX in breast cancer indicated that 4'-epi-DX may have a lower cumulative cardiotoxicity.
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PMID:4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. 634 72

The experimental antitumor activity of a new mitomycin derivative, 7-cysteaminomitosane (RR-150), was evaluated in mice. When administered i.p. to mice bearing i.p.-implanted tumors, RR-150 was superior to mitomycin C (MMC) in increasing the life span of animals bearing P388 leukemia, B16 melanoma, and a line of L1210 leukemia partially resistant to MMC. RR-150 appeared comparable to MMC in increasing life span of mice bearing Madison 109 lung carcinoma, Colon 26 carcinoma, or parental (nonresistant) L1210 leukemia. Mice immunosuppressed with 550 rads whole-body irradiation prior to i.p. implantation of B16 still benefited (e.g., 40% cure rate) following optimal RR-150 therapy when compared to nonirradiated, B16-implanted mice given RR-150 (e.g., 70% cure rate). RR-150 had inconsistent activity in the treatment of s.c.-implanted tumors. In toxicity evaluations, RR-150 was comparable to MMC in suppression of total while blood cell counts but appeared to be less neutropenic. RR-150 also caused less cumulative leukopenia than did MMC in a weekly chronic dose experiment. Based on serum chemistries, RR-150 did not have significant nephrotoxicity, but there was evidence of possible liver toxicity at doses near the 50% lethal dose. Because of the balance of favorable antitumor and toxicity properties of RR-150, work is under way to prepare a more bioavailable form for advanced evaluation.
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PMID:Antitumor activity and toxicity in animals of RR-150 (7-cysteaminomitosane), a new mitomycin derivative. 643 70

This study describes a comparison of 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) and imidazole-4-carboxamide,5-(3,3-dimethyl-1-triazeno) (DTIC) with reference to antitumor activity on different murine tumors and hematological toxicity. DM-COOK appeared comparably or slightly more effective in L1210, P388, and M5 tumors in the mouse. However, when the treatment of mice bearing M5 with DM-COOK was combined with surgical removal of the primary tumor, the host's life-span was highly significantly prolonged. The two drugs showed similar activity in an M5 variant selected for resistance to cyclophosphamide. In L1210 Ha, a leukemia that is spontaneously resistant to DTIC, DM-COOK was not effective. Both DM-COOK and DTIC caused transient leukopenia with a maximum WBC fall of 57% and 71% compared with control values. DM-COOK's greater chemical stability might be an advantage, as the decomposition of DTIC is thought to lead to products responsible for some toxic effects in humans. Like other phenyldimethyltriazenes DM-COOK, is a good candidate for clinical trials because its water solubility eliminates formulation problems.
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PMID:Comparison of the antitumor activity of DTIC and 1-p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt on murine transplantable tumors and their hematological toxicity. 646 99


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