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)

Thirty-four new cases of acute promyelocytic leukaemia (M3) were diagnosed at the authors' Centre between 1970 and 1988 (19 males and 15 females) with ages between 5 and 73 years (median age, 32 years). Three cases were of the hypogranular variant or M3-v (8.8%). The clinical picture included: haemorrhagic diathesis (85%), pallor/malaise (82%), fever/infection (41%), hepatomegaly (26%), splenomegaly (12%). Leucopenia of less than 5 x 10(9)/L was present in 23/34 cases, laboratory signs of DIC in 26/31, increased LDH, over 400 U/mL, in 6/31, and abnormal karyotype in 7/15. One of the patients rejected any treatment; two others died of brain haemorrhage before therapy was started, and seven died in the first two weeks of treatment. Of the 31 patients treated, complete remission (CR) was achieved in 21 cases (67.7%). Allogeneic BMT was carried out in two of them, with further relapse and death. Post-remission treatment was given to the remaining 19 patients, and there were 13 relapses. Six patients have been in CR, 5 of them after cessation of therapy, for the last 1.5-11.5 years. Age under 50 years and leucocyte count below 5 x 10(9)/L at diagnosis were favourable prognostic factors according to the univariate statistical analysis performed. The survival plateau of the actuarial curve was reached beyond 2.75 years by 15% of all the patients treated (33 cases), 23% of the patients who achieved CR (21 cases), 31% of the patients under 50 years of age and 5 x 10(9)/L leucocyte count at diagnosis (15 cases) and 36% of these last achieving CR (13 cases).
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PMID:[Acute promyelocytic leukemias: clinico-biological aspects, prognostic factors, therapeutic response, and possibilities of cure in 34 cases (1970-1988)]. 218 63

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.
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PMID:An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. 223 Aug 78

The West Japan Pediatric Oncology Group studied the treatment of pediatric malignant tumors with VP-16 from December 1984 to March 1988. Study subjects were divided into two groups. One group received only VP-16, while the other received VP-16 combined with other anti-tumor agents. VP-16 evaluation was possible in a total of 116 cases. The efficacy rate was calculated by considering both complete and partial remission as effective. The efficacy rate for VP-16 alone was 87.5% for primary cases of ANLL and 100% for primary cases of histiocytosis. The efficacy rates for combination therapy were as follows: 92.6% for primary cases of ANLL, 66.7% for primary cases of histiocytosis, 45.5% for relapsed cases of ANLL and 66.7% for relapsed cases of ALL. Bone marrow suppression was seen in the form of leukopenia and thrombocytopenia for 2 to 3 weeks after VP-16 administration. Alopecia, mucositis and gastrointestinal symptoms were also observed, but they presented no significant problem. From our results, we believe that chemotherapy including VP-16 is effective for remission induction therapy in primary cases of ANLL and for salvage therapy in relapsed leukemia. Additionally, VP-16 is considered to be effective for the treatment of histiocytosis.
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PMID:Treatment of pediatric malignant tumors with VP-16. West Japan Pediatric Oncology Group. 223 3

It has been reported that in vitro uridine (Urd) can reverse azidothymidine (AZT) cytotoxicity without decreasing anti-human immunodeficiency virus (HIV) activity. Our studies in mice have shown that daily oral doses of benzylacyclouridine (BAU), an inhibitor of Urd breakdown, also reduces AZT hematologic toxicity, presumably by elevating the plasma concentration of Urd. We now extend these murine studies and report the effect of various doses of exogenous Urd, various doses of BAU, or the combination of BAU and Urd, administered daily, on AZT-induced toxicity. In mice receiving concomitant AZT, daily doses of Urd of 1,000 to 2,000 mg/kg increase peripheral reticulocytes and slightly reduce AZT-induced hematologic toxicity. However, the range of effective doses is narrow, and higher doses of Urd (greater than 3,000 mg/kg/d) significantly enhance hematologic toxicity. At its most effective dose, (2,000 mg/kg/d), Urd produces 28% mortality. In contrast, BAU doses up to 300 mg/kg/d reduced AZT-related hematologic toxicity in a dose-dependent manner without mortality. Higher daily doses of BAU and the combination of BAU with low doses of Urd were not more effective. Studies conducted in mice infected with the Rauscher murine leukemia virus (RLV) indicate that BAU does not impair the antiretroviral effect of AZT when administered at doses that reduce AZT-induced anemia and leukopenia. These findings may be significant for the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.
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PMID:Different effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice. 225 95

One hundred and thirty-three cases of myelodysplastic syndromes studied during the last ten years were revised. Of them, 79 were males and 54 females, and their ages ranged between 15 and 91 years (median, 69 years). Five patients (3.7%) had secondary myelodysplasias. The haematological phenotype (FAB) of the cases was: RA, 41.3%; SRA, 24%; RAEB, 18%; RAEBT, 3.7%; CMML, 8.3%. Leucopenia/thrombocytopenia without initial anaemia was present in 4.5% of the cases. Abnormal karyotype was found in 54 patients (40.6%), MIKA in 41 cases and MAKA in 13 cases. The cytogenetic anomalies most commonly found were +8, 5q-, -7, 11q- and 13q-. Cytogenetic abnormalities were commonest amongst the RAEB (50%), and least frequent in CMML (18.2%). Thirty-one patients evolved into acute leukaemia (29 ANLL and 2 ALL). Such blastic changes were more frequent in RAEB (62.5%) and rarest in SRA (9.4%), and they appeared mostly in patients with complex karyotype (MAKA) (53.8%) as compared with those who had normal karyotype (17.7%). Short-lasting complete remission was achieved by 40% of the patients treated with conventional chemotherapy. The survival of the group as a whole (median 30 months) varied in accordance with the haematological phenotype: SRA, 81 months; RA, 65 months; CMML, 13 months; RAEB +/- T, 8 months. The finding of a MAKA karyotype significantly shortened the survival (4 months) with regard to MIKA (44 months) or normal karyotype (39 months). The following median survivals were attained after patients' staging (Bournemouth's criteria): stage A, 84 months; stage B, 22 months, and stage C, 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Myelodysplastic syndromes. Hematologic phenotypes, cytogenetic expression and clinical course in 133 cases (1979-1989)]. 227 38

A series of new water soluble sugar and non-sugar containing platinum(II) complexes was synthesized and evaluated for effects of the sugar moiety on water solubility, anti-tumor activity, and acute leukopenia. When tested in vivo against the murine P388 and L1210 leukemias at LD10/maximally effective doses, the compound cis-[(gluconylamino)malonato-O,O'](1R,2R-cyclohexanediami ne-N,N')platinum (II), R,RG-AMP produced comparable or superior anti-tumor activity to cisplatin, carboplatin, and tetraplatin. Efficacy was also demonstrated for the L1210/DDP (cisplatin-resistant) leukemia. Further, R,R-G-AMP is non-nephrotoxic and produces less leukopenia than cisplatin, carboplatin, and tetraplatin.
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PMID:Murine anti-tumor activity of new water soluble platinum(II) complexes with reduced toxicity. 229 75

A phase II study was conducted by the Cancer and Leukemia Group B (CALGB) in patients with refractory and relapsed Hodgkin's disease (HD) to assess the activity of the combination of etoposide and cis-platin. Twenty-seven patients were entered; 22 were evaluated for this report. Treatment consisted of etoposide (VP-16), 80 mg/m2 IV over 1 hour and cis-platin, 20 mg/m2 IV over 1/2-1 hour; both agents were given daily for 5 days and repeated every 21 days. All patients had received at least 2 prior chemotherapy regimens, had measurable disease, and most (86%) had a performance status of 0-1. In the 22 evaluable patients, there were 4 complete responses (18%) and 4 partial responses, for an overall response rate of 36% (95% Cl: 17.2%, 59.3%). Response duration was from 2.1 to 31 months. Significant toxicity was observed with this regimen. Ten patients (45%) had leukopenia less than 1,000/microliters, and 11 patients (50%) had thrombocytopenia less than 25,000/microliters. Serum creatinine levels reached greater than 2.0 in 14% of patients. Seven patients (32%) had severe nausea and vomiting. VP-16, cis-platin appears to be an active combination in HD; however, their combined activity is only marginally better than reported single-agent activity for VP-16 in the doses and schedule used. Further studies of related combinations in HD are currently under evaluation by the CALGB.
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PMID:Phase II trial of etoposide and cis-diaminodichloro-platinum in patients with refractory and relapsed Hodgkin's disease: Cancer and Leukemia Group B (CALGB) Study 8353. 232 62

Clostridium septicum is a major cause of spontaneous, nontraumatic gas gangrene. Unlike Clostridium perfringens, C. septicum is relatively aerotolerant and thus appears to be more capable of initiating infection in the absence of obvious damage to tissues. Six cases illustrate the clinical setting and fulminant nature of spontaneous gangrene caused by C. septicum. A lesion in the colon such as carcinoma is often present and is presumed to serve as a portal of entry to the bloodstream. Diabetes and leukopenia are also common predisposing conditions; compromise of vital host responses may facilitate proliferation of those organisms that settle out in the tissues. Acute lymphoma or leukemia during a course of chemotherapy is accompanied by damage to bowel mucosa and granulocytopenia, thus predisposing to spontaneous clostridial gangrene. Infection progresses in a fulminating manner; the majority of patients die within 24 hours of onset. Characteristic symptoms and signs include excruciating pain (although a sense of heaviness may be the only early symptom), swelling of tissues, crepitance, and bulla formation. A hallmark of C. septicum infection is the absence of acute inflammatory cells in involved tissues or in bulla fluid. A series of laboratory investigations demonstrated that fluid obtained from a bulla adversely affected the viability, morphology, and function of polymorphonuclear leukocytes (PMNs), which may explain the paucity of PMNs in involved tissues and may in part contribute to the fulminant progression observed in infection due to this organism.
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PMID:Spontaneous, nontraumatic gangrene due to Clostridium septicum. 233 Apr 82

An acute myelomonocytic leukemia presenting transient skin rash during preleukemic phase was described. Following four years of unexplained leukopenia, a generalized exanthema developed and subsequently regressed spontaneously. The skin biopsy and immunohistochemistry revealed monocytic infiltration into the dermis. Twenty-eight months later, the patient became leukemic and died. The skin lesions, however, did not occur after leukemic transformation. Probably transient monocytic skin infiltrate was a symptom of preleukemia, a stem cell neoplasm manifested by functionally abnormal maturation.
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PMID:[Transient monocytic skin infiltrate during preleukemic phase of acute myelomonocytic leukemia]. 236 46

The in vitro effect of recombinant human GM-CSF (rHuGM-CSF) was tested on bone marrow-derived multilineage (CFU-GEMM) as well as megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitors in a group (n = 16) of patients with myelodysplastic syndromes (MDS). Hematopoietic progenitor cell growth was markedly impaired in MDS patients as compared to normal controls (p less than 0.05, at least). Recombinant HuGM-CSF supported the growth of CFU-GEMM, CFU-Mk, and BFU-E at lower, equivalent, or slightly higher frequencies that those found in cultures plated with medium conditioned by peripheral blood leukocytes (PHA-LCM), but it was invariably ineffective in improving growth values. Recombinant HuGM-CSF supported the growth of granulocyte-macrophage colonies in 15 of 16 cases. The overall incidence (mean +/- SEM) of CFU-GM in cultures containing rHuGM-CSF (5 ng/ml) was significantly higher than the one found in cultures stimulated with PHA-LCM (40 +/- 15 vs. 17 +/- 7, p less than 0.05). Upon culture with rHuGM-CSF (5 ng/ml), in 5 of 15 patients de novo colony formation was observed (8 +/- 4) and in 4 of 15 patients CFU-GM growth (129 +/- 33) fell within normal range. Doses of rHuGM-CSF higher than 5 ng/ml did not result in a further increase of MDS-derived colony formation. It is concluded that rHuGM-CSF (a) does not improve the growth of CFU-GEMM, CFU-Mk, and BFU-E; (b) may completely restore the growth of CFU-GM in a subgroup of MDS patients; (c) while ineffective in improving anemia and thrombocytopenia, its in vivo in MDS may correct leukopenia through an effect at the level of granulocyte-macrophage progenitor cell compartment, at least in a subset of highly responsive patients.
Leukemia 1989 May
PMID:Growth of human hematopoietic colonies from patients with myelodysplastic syndromes in response to recombinant human granulocyte-macrophage colony-stimulating factor. 265 96


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