Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.
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PMID:Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. 220 4

We previously administered ara-C at a dose rate of 250 mg/m2/hr for 36-72 hr to patients with leukemia. Gastrointestinal toxicity was dose-limiting. This regimen was modified to an every other day schedule, administering 24-hr periods of high dose continuous infusion ara-C, each followed by a 24-hr rest period. Sixteen patients with relapsed/refractory acute myeloid leukemia (AML) (N = 4), secondary AML (N = 2), relapsed/refractory acute lymphoblastic leukemia (N = 7), or CML in blast crisis (N = 3) received this regimen of three 24-hr infusions with two intercurrent 24-hr rest periods. Grade 3 gastrointestinal toxicity was encountered in 57% of the courses, and hypoplasia was achieved in all patients. Three of the patients died while hypoplastic, two with septicemia and another with intracranial hemorrhage. There were five responding patients (2 CRs, 3 PRs). Median steady-state plasma ara-C levels were 24 microM, 22 microM, and 20 microM during the first, second, and third 24-hr infusions, respectively. Ara-C levels ranged from 4-118 microM during the infusions and were always below 4.5 microM during the rest periods. A significant level of ara-C incorporation into DNA was detected in each of the five patients studied, thus demonstrating that (ara-C)DNA formation is detectable in blasts from patients receiving high dose continuous infusion ara-C therapy. These findings suggest that alternate day continuous infusion ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
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PMID:A phase I study of intermittent continuous infusion high dose cytosine arabinoside for acute leukemia. 224 7

A case of Philadelphia (Ph1) chromosome positive acute myelogeneous leukemia (AML) following a refractory anemia with excess of blasts (RAEB) with 8 trisomy is reported. The 80-year-old man developed pancytopenia during the course of follow-up after the surgical operation of the carcinoma of the sigmoid colon and the rectum for which no irradiation therapy nor chemotherapy had been applied. The diagnosis of RAEB was made according to the diagnostic criteria proposed by FAB co-operative group. Chromosomal analysis revealed 8 trisomy in 54% of the metaphases of bone marrow cells. The remainders showed normal karyotype without Ph1 chromosome. He was on androgenic steroid and activated Vitamin D3 without significant changes in the clinical and the hematological features until 3 months later when many atypical blasts appeared in the peripheral blood. The diagnosis of AML (M2) was made. Chromosomal analysis revealed Ph1 chromosome with the typical 9;22 translocation in 100% of the examined cells. 8 trisomy was not detected any more. Southern blot analysis using bcr probe showed bcr rearrangement. He was treated with a small doses of Ara-C. There was some reduction in the number of blasts in the peripheral blood. However, he died of septicemia 2 months later. The present case indicates that Ph1 positive acute leukemia with bcr rearrangement is not necessarily considered as a blastic transformation of chronic myelogeneous leukemia and such a cytogenic abnormality can appear in a leukemic transformation of myelodysplastic syndrome.
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PMID:[Acquisition of Philadelphia chromosome with bcr rearrangement concomitant with transformation of refractory anemia with excess of blasts with 8 trisomy into acute myelogenous leukemia]. 236 38

Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further.
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PMID:Combination chemotherapy with cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract. 258 30

Four hundred ninety evaluable patients were treated on an induction regimen consisting of two to four courses of cytosine arabinoside plus an anthracycline. Overall, 78% of patients went into remission, 10% died during induction, and 12% were induction failures. For the first 152 patients, courses consisted of 7 days continuous infusion with cytosine arabinoside (Ara-C, 100 mg/m2) and 3 days of doxorubicin (30 mg/m2). Because of unacceptable toxicity, particularly for children less than 3 years of age, the anthracycline was changed to daunorubicin, and the doses of both induction drugs for children under 3 was reduced. For children aged 3 years and older the change in anthracycline was associated with a significant increase in induction failures (7% to 16%, P = .04) and a decrease in deaths (15% to 8%, P = .09). For younger children, for whom doses were also changed, the effect was greater; Mortality decreased from 29% to 1% (P less than .0001), and the remission induction rate increased from 66% to 88% (P = .005). The therapy modifications also influenced survival following remission induction: Daunorubicin-treated patients, aged 3 years and over, did significantly better than those given doxorubicin (P = .03), but the opposite was seen in younger children (P = .06). Gastrointestinal and skin toxicities and septicemia were significantly more common when doxorubicin was being used, but the extent of myelosuppression was similar for the two anthracyclines.
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PMID:Remission induction in children with acute non-lymphocytic leukemia using cytosine arabinoside and doxorubicin or daunorubicin: a report from the Childrens Cancer Study Group. 267 28

As increasing numbers of children and adults with leukemia have become long-term survivors, the impact of an existing pregnancy on leukemia treatment, as well as the significance of prior leukemia therapy on future pregnancies, have become sources of concern. The information presently available, derived from small, retrospective series or case reports, indicates that leukemia may develop throughout pregnancy, that a leukemia woman who is pregnant need not undergo an abortion if she does not desire, and that standard antileukemic chemotherapy can be administered safely during the second and third trimesters. The antifolates (eg, methotrexate), being particularly teratogenic, should be avoided during the first trimester. Cytarabine and anthracycline treatment, the fundamental components of management for patients with AML, has not been associated with birth defects. The risk for placental injury, sepsis, and spontaneous abortion or premature birth is undoubtedly increased in women who experience the periodic episodes of myelosuppression that accompany leukemia treatment. Once remission has been achieved, decisions regarding adjustments of the intensity of therapy must be made with each individual patient; such dose alterations may diminish the mother's potential for long-term leukemia control, while possibly securing the viability of the fetus. Similarly, issues such as elective delivery prior to term and vaginal delivery v caesarean section should be resolved on a patient-by-patient basis. The offspring of leukemic mothers appear to mature normally.
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PMID:Pregnancy and leukemia. 267 88

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.
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PMID:Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma. 277 81

Thirty-five patients with acute myelogenous leukemia were treated with aclacinomycin A (60 mg/m2/day for 5 days) and VP-16-213 (100 mg/m2/day for 5 days). All were previously treated and had relapsed or were refractory to primary treatment. Most patients (28) had received prior DAT (daunorubicin, cytosine arabinoside, and 6-thioguanine) induction therapy followed by one or more courses of high-dose cytosine arabinoside (HD-Ara C) as consolidation therapy or as treatment for relapse. One patient was in her fourth relapse, one had relapsed acute megakaryoblastic leukemia (following remission with DAT and HD-Ara-C), one had a treatment-induced leukemia, and four patients were treated for primary treatment failures following two induction courses with DAT or a similar regimen. Fourteen patients had infections at start of therapy. Ten patients died within 14 days of treatment, all from sepsis or bleeding, before their marrow could be evaluated for leukemic response. Fourteen patients (40%) responded; 12 (34%) entered complete remission and two (6%) a partial remission (PR). Two of the four patients who were treated for primary treatment failures went into CR. The median CR duration was 99 days (range 30 to 455 days). Side effects from this treatment were similar to the conventional DAT regimen, although the gastrointestinal toxicity and mucositis appeared to be more severe. In addition, two of the patients had severe but reversible ventricular arrhythmias. The overall response (40%) and CR rate (34%) in this group of previously treated AML patients is encouraging, and further studies are needed to evaluate these preliminary findings.
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PMID:Aclacinomycin A and etoposide (VP-16-213): an effective regimen in previously treated patients with refractory acute myelogenous leukemia. 316 95

Neutrophilic eccrine hidradenitis (NEH) is a recently described neutrophilic dermatosis associated with acute myelogenous leukemia (AML) and chemotherapy. This disorder is a distinct clinicopathologic entity separate from leukemid reactions and other neutrophilic dermatoses. We describe two cases in which plaques or nodules developed in the second week after initiation of induction chemotherapy for AML. The lesions regressed in 1 week and recurred in one case when induction chemotherapy was given a second time. Histologically, the findings were similar in each case. Neutrophils palisaded about and infiltrated the eccrine coil in which necrosis of secretory epithelium was present. Focal mucinous degeneration of the eccrine adipose tissue cuff was the only other significant alteration. No vasculitis was observed. Cultures and histologic preparations for pathogenic organisms were negative. Cytarabine was the chemotherapeutic agent used in all three cases. NEH most likely represents either an unusual response caused by cytarabine or a manifestation of AML. Recognition of NEH is important in order to exclude other neutrophilic dermatoses associated with AML, such as sepsis and leukemia cutis, which may appear clinically similar.
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PMID:Neutrophilic eccrine hidradenitis: a distinctive rash associated with cytarabine therapy and acute leukemia. 623 61

The human normal intestinal flora prevents the colonization of exogenous bacteria, maintaining a constant microecology: this property is called "colonization resistance". In leukemia patients antibiotics used for prevention and/or therapy of infectious episodes can alter the intestinal microecology, so that the gut can represent the trigger zone for generalized septicemia. Moreover cytotoxic drugs used in these patients can favour intestinal disturbances. In our study we evaluated the in vitro activity of three commonly used antineoplastic drugs (Daunorubicin, Cytosine arabinoside, Methotrexate) against aerobic and anaerobic intestinal bacteria and Clostridium difficile that is the aetiological agent of pseudomembranous colitis. Daunorubicin proved to be the most active inhibiting, in concentration ranging from 16 to 128 micrograms/ml, 50% of Bacteroides strains and 90% of Clostridium difficile and Enterococci strains tested. Methotrexate showed activity only against some Bacteroides strains, while Cytosine arabinoside had no activity at all. We conclude that in these patients the use of these drugs may represent another factor of risk altering the intestinal flora and so lowering the colonization resistance.
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PMID:[In vitro activity of several cytostatic drugs against aerobic and anaerobic intestinal bacteria]. 653 96


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