Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor.

Purpose: To determine whether granulocyte colony-stimulating factor (G-CSF) administered before, during, and after fludarabine plus cytarabine (ara-C; FA) chemotherapy affected complete response (CR) rate, infection rate, blood count recovery, or survival in patients with newly diagnosed acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS).

Patients And Methods: A total of 112 patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400 micrograms/m2/d 1 day before (presenting WBC count < 50,000/microL) and/or during (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF continued until a CR was achieved.

Lack of effect of 2-chlorodeoxyadenosine therapy in patients with chronic lymphocytic leukemia refractory to fludarabine therapy.

Background: Fludarabine and 2-chlorodeoxyadenosine are nucleoside analogues that have proved effective in patients with chronic lymphocytic leukemia (CLL). Although their mechanism of action is thought to be similar, a small number of patients who do not respond to fludarabine do respond to 2-chlorodeoxyadenosine. The extent to which 2-chlorodeoxyadenosine is effective in patients who do not respond to fludarabine is not known, however.

A phase I trial of weekly lomustine in patients with advanced cancer.

Background: Lomustine is a commercially available chloroethyl nitrosourea compound whose antitumor activity in vitro and in animal tumor models exceeds its activity in humans. Part of the poor clinical performance of this drug may be explained by dose-limiting subjective toxicity observed with the standard schedule of one oral dose of approximately 130 mg/m2 every 6-8 weeks.

Methods: Twenty patients were enrolled in a Phase I clinical trial of weekly oral lomustine.

Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment.

Two hundred sixty-four patients with chronic lymphocytic leukemia were treated with fludarabine 30 mg/m2 intravenously for 30 minutes each day for 5 days and with prednisone 30 mg/m2 orally each day for 5 days. Courses were repeated monthly. Of the 264 patients.

Platelet crossmatches of single-donor platelet concentrates using a latex agglutination assay.

A latex agglutination assay was evaluated for the purpose of identifying compatible platelet donors for alloimmunized recipients. Assay reagents were prepared by adsorbing detergent-solubilized, donor-specific platelets to polystyrene latex beads. Semiquantitative results for up to 30 donors can be completed in less than 1 hour.

An open trial of cefoperazone plus sulbactam for the treatment of fever in cancer patients.

Cancer patients received cefoperazone plus sulbactam for 673 febrile episodes presumed to be caused by infection. Overall, 415 (76%) of the 545 evaluable episodes responded. There were 213 responses (84%) amongst the 254 fevers of unknown origin and 202 responses (69%) amongst the 291 documented infections.

Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent.

The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents.

Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule.

The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/m2 fludarabine given every three to four weeks.

Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia.

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course.

Nucleoside analogs in treatment of chronic lymphocytic leukemia.

The nucleoside analogs fludarabine monophosphate, 2-chlorodeoxyadenosine, and 2-deoxycoformycin (pentostatin) all have activity in chronic lymphocytic leukemia. The most widely studied drug is fludarabine which is able to obtain complete or partial responses in more than 50% of previously treated patients. The response rate is 44% for 2-CDA and approximately 25% for pentostatin.

Determination of plicamycin in plasma by radioimmunoassay.

This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method.

Technology management information exchange (TEMINEX). Applied technology assessment for HMOs.

In an effort to obtain timely, comprehensive and valid information, The HMO Group medical directors have pooled resources to facilitate decision-making on the appropriate use of new or unfamiliar technologies. The HMO Group has responded to over 175 requests for information on topics such as organ transplants, testing and screening procedures, drugs and devices.

Treatment of newly diagnosed acute myelogenous leukemia with granulocyte-macrophage colony-stimulating factor (GM-CSF) before and during continuous-infusion high-dose ara-C + daunorubicin: comparison to patients treated without GM-CSF.

We gave 56 patients with newly diagnosed acute myelogenous leukemia (AML) granulocyte-macrophage colony-stimulating factor (GM-CSF) 20 or 125 micrograms/m2 once daily subcutaneously before (for up to 8 days or until GM-CSF-related complications developed) and during, or only during (patients presenting with blast counts greater than 50,000 or other leukemia-related complications) ara-C (1.5 g/m2 daily x 4 by continuous infusion) and daunorubicin (45 mg/m2 daily x 3) chemotherapy. Because results seemed independent of GM-CSF schedule, we compared results in these 56 patients with results in 176 patients with newly diagnosed AML given the same dose and schedule of ara-C without GM-CSF (110 patients ara-C alone, 66 patients ara-C + amsacrine or mitoxantrone).

Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine.

Purpose: To evaluate the efficacy of interferon-alpha (IFN-A) and low-dose cytarabine (ara-C) combination chemotherapy in patients with chronic myelogenous leukemia (CML).

Patients And Methods: Sixty patients with advanced phases of Philadelphia chromosome (Ph)-positive CML received combination therapy with IFN-A 5 x 10(6) U/m2 daily, and low-dose ara-C 15 mg/m2 daily for 2 weeks every 4 weeks until remission, then for 1 week every month as maintenance. Forty patients were in late chronic-phase CML, and 20 were in accelerated-phase CML (16 with clonal evolution only, four with other criteria).

Characterization of the pH-mediated solubility of Bacillus thuringiensis var. san diego native delta-endotoxin crystals.

Native crystals of Bacillus thuringiensis var. san diego, a coleopteran-specific delta-endotoxin, were metabolically labelled with [35S]methionine. Specific activity was 82,000 CPM/micrograms (2.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA).

We administered one course of 2-chlorodeoxyadenosine (2CdA) at 4 mg/m2 daily for 7 days by continuous intravenous infusion to 46 patients with hairy cell leukemia. Complete remissions occurred in 36 patients (78%; 95% confidence limits, 63% to 89%), partial remissions in five (11%), and a minor response in one. One patient died of candida sepsis 3 weeks after beginning treatment and three patients were clearly resistant to therapy.

Mithramycin inhibits SP1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo.

The promoter of the human dihydrofolate reductase (DHFR) gene contains two consensus binding sites for the DNA binding protein Sp1. DNAse protection and gel mobility shift assays demonstrate binding of recombinant Sp1 to both decanucleotide Sp1 binding sequences which are located 49 and 14 base pairs upstream of the transcription start site. The more distal of the two binding sites exhibits a somewhat higher affinity for Sp1.

Mitoxantrone and high-dose etoposide for patients with relapsed or refractory acute leukemia.

Among 35 patients with relapsed or refractory acute myelogenous leukemia (AML) who received salvage chemotherapy, 28 were treated with mitoxantrone (7.5 mg/m2/d intravenously [IV] over 1 hour for 5 days) and etoposide (VP-16) (2 g/m2 over 4 days either as a daily infusion or as two daily doses). Seven patients received mitoxantrone (6 mg/m2/d for 5 days) and VP-16 (1500 mg/m2 over 3 days).

Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever.

Cancer patients were randomized to receive an every 4 hour or every 8 hour schedule of cefoperazone plus aztreonam during 617 febrile episodes. The overall response rate for the 478 evaluable episodes was 76% and there was no difference in response rate between the two schedules. The response rate was 79% for cases of pneumonia and 63% for cases of bacteremia.