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)

One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3-17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1-4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor.
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PMID:One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. 1 51

Structure-activity studies of nitrosourea pharmacology have resulted in the synthesis of a new water-soluble agent,chlorozotocin, which has significant antitumor activity against the L1210 leukemia system and produces only a minor degree of inhibition of mouse and human bone marrow DNA synthesis compared to BCNU. It is important to emphasize that the bone marrow sparing feature of chlorozotocin is relative and that if the drug is administered at lethal dose levels in mice, myelosuppression is observed. The potential importance of these studies is the identification of a new and active nitrosourea antiumor agent with modified bone marrow toxicity. If aminoglucose modification of nitrosourea bone marrow toxicity can be confirmed in man without significant loss of antitumor activity, the use of such a compound could facilitate treatment of patients with neoplastic disease who have pre-existing abnormal bone marrow function. It would also allow the more effective use of a nitrosourea agent in combination with anticancer agents possessing more potent myelosuppressive properties.
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PMID:Pharmacology of chlorozotocin Nsc-178248), a new nitrosourea antitumor agent. 13 56

The synthesis of new analogs of the anticancer agent BCNU is described. It involves the preparation of N-(2-chloroethyl)-N-nitrosocarbamoylazide and its reaction with aliphatic diamines and aminoalcohols to yield 1,1'-polymethylenebis 3-(2-chloroethyl)-3-nitrosoureas and 1-(omega-hydroxyalkyl)-3-(2-chloroethyl-3-nitrosoureas. Screening for chemotherapeutic activities of the newly synthesized nitrosoureas against rat leukemia L 5222 and s.c. Walker carcinosarcoma 256 revealed remarkable differences between individual compounds. The water soluble 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrousourea was the most active compound of this series, effecting 90% cures in i.p. inoculated L5222 leukemia.
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PMID:Some new congeners of the anticancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Synthesis of bifunctional analogs and water soluble derivatives and preliminary evaluation of their chemotherapeutic potential. 13 2

Two patients treated for acute leukaemia with BCNU, cyclophosphamide and cytosin-arabinoside are reported, in whom pulmonary fibrosis developed and progressed during therapy. The development of lung fibrosis during combined treatment, together with serological exclusion of other diseases known to be associated with pulmonary fibrosis, make a causal connection between the treatment and the fibrosis very probable.
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PMID:[Progressive pulmonary fibrosis due to combined treatment with BCNU, cyclophosphospahmide and cytosin-arabinoside (author's transl)]. 15 Oct 43

The newly synthesized nitrosoureas 1-(2-chloroethyl)-1-nitroso-3-(methylenecarboxamido)-urea (Acetamido-CNU), 1-(2-chloroethyl)-1-nitroso-3-(4-morpholino)-urea (Morpholino-CNU), 1-(2-chloroethyl)-1-nitroso-3-(1-piperidino)-urea (Piperidino-CNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-ethylmethanesulfonate (Ethylmethanesulfonato-CNU) were compared in their chemotherapeutic activity against preterminal rat leukemia L 5222 with BCNU, CCNU, MeCCNU, Chlorozotocin, and Hydroxyethyl-CNU. With respect to the dose range effecting a median survival time of more than 90 days, MeCCNU was superior to the other substances. Chlorozotocin, on the other hand, was the only substance which achieved no cures in this experimental arrangement. From the four newly introduced substances the water-soluble substances Acetamido-CNU and Morpholino-CNU were approximately comparable to CCNU with regard to the dose range effecting a median survival time of greater than 90 days. Piperidino-CNU and Ethylmethanesulfonato-CNU also effected cures; however, only Piperidino-CNU in one dosage effected a median survival time of greater than 90 days.
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PMID:Examination of four newly synthesized 2-chloroethylnitrosoureas in comparison with BCNU, CCNU, MeCCNU, chlorozotocin and hydroxyethyl-CNU in preterminal rat leukemia L 5222. 15 9

After cure of rat leukemia L 5222 in 79 BD IX rats by single doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-hydroxyethyl)-3-(2-chloroethyl)-3-nitrosourea (Hydroxyethyl-CNU) a total of 9 rats (11%) developed secondary malignomas.
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PMID:Development of second malignancies in rats after cure of acute leukemia L 5222 by single doses of 2-chloroethylnitrosoureas. 22 10

Seven patients with metastatic tumors resistant to therapy with adriamycin, BCNU, plus cyclophosphamide received the same chemotherapy combined with amphotericin B. One complete response (acute myelomonocytic leukemia), two partial responses (carcinoma of the breast and multiple myeloma), and one case with objective improvement (carcinoma of the breast) were observed in seven evaluable trials. Myelosuppression was not consistently changed by addition of amphotericin B. Fever and chills were common after amphotericin B. Bronchospasm and hypotension occurred twice. Amphotericin B reverses resistance to adriamycin-containing chemotherapy regimens in some patients.
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PMID:Amphotericin B induction of sensitivity to adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) plus cyclophosphamide in human neoplasia. 26 83

Two hundred and twenty-seven children with recurrent acute lymphoblastic leukemia were treated with various combinations of vincristine, prednisone, cyclophosphamide and L-asparaginase in an approach to the induction of remission. The combination of L-asparaginase 1,000 mu/kg iv q.d. x 10, vincristine 2.0 mg/m2iv q.w. x 4 and prednisone 40 mg/m2 p.o.q.d. x 28 days was found to be highly effective. The incidence of remission was 73%. No significant improvement was achieved when cyclophosphamide was added to this regimen. Various combinations of cytosine arabinoside, cyclophosphamide, vincristine, prednisone, BCNU or CCNU failed to maintain remission duration for more than two or three months. Neither BCNU nor CCNU prevented the development of CNS leukemia.
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PMID:Vincristine, prednisone and L-asparaginase in the induction of remission in children with acute lymphoblastic leukemia following relapse. 27 45

We assayed the femoral marrows of individual AKR mice for leukemia colony-units (LCFU) after treatment with amphotericin B (AmB) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with BCNU alone. No differences between the groups were noted in the first 7 days after treatment. All the mice treated with BCNU alone were dead by day 8, and all the survivors among the animals receiving AmB and BCNU retained high levels of LCFU for 2 more days; these LCFU were subsequently rejected by the host. By day 12, LCFU were undetectable. Histologic examination of organs from the same mice on day 5 showed fewer leukemia cells in the mice treated with the combination of agents. In all treatment groups, mice dying of leukemia early (by day 9) had systemic leukemia and most had central nervous system (CNS) involvement. All animals dying between days 10 and 14 had CNS leukemia, but few had systemic leukemia; at later times, though few animals died, they invariably had CNS leukemia without systemic involvement.
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PMID:Growth and rejection of leukemia cells in individual mice after combined treatment with amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea. 27 27

cis-Dichlorodiammineplatinum(II) (cis-platinum) has no more than additive, and often much less than additive, lethal toxicity for mice when given in combination with other anticancer agents representing several of the major functional classes of clinically useful anticancer drugs. The previously reported broad spectrum of anticancer activity of cis-platinum against tumors in laboratory animals has now been extended to promisingly useful therapeutic synergism in combination with other active anticancer drugs, including advanced-staged tumors in mice; eg, cis-platinum plus cyclophosphamide against advanced Ridgway osteogenic sarcoma and advanced P388 leukemia, and as surgical adjuvant chemotherapy against advanced colon tumor 26; cis-platinum plus Adriamycin against advanced P388; and cis-platinum plus VP-16-213 against advanced P388. Therapeutic synergism was also seen with cis-platinum plus carminomycin (an Adriamycin analog) against early colon tumor 26. Resistance and cross-resistance studies using sublines of L1210 and P388 selected for resistance to various alkylating agents (cyclophosphamide, melphalan, BCNU, or cis-platinum) indicate a variety of resistance and cross-resistance patterns which further support the growing body of evidence that wide differences in mechanism of cytotoxic activity exist among alkylating agents having experimentally and clinically useful anticancer activity. These data support the observed therapeutic synergisms with combinations of alkylating agents seen against a broad spectrum of murine tumors, and they suggest other drug combinations that might be considered for experimental and clinical trial based on a growing number of logical differences in biochemical mechanism of action of alkylating agent anticancer drugs that have been reported.
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PMID:cis-Dichlorodiammineplatinum(II): combination chemotherapy and cross-resistance studies with tumors of mice. 29 80


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