scholarly journals Ceftazidime in Acute Myeloid Leukemia Patients with Febrile Neutropenia: Helpfulness of Continuous Intravenous Infusion in Maximizing Pharmacodynamic Exposure

2005 ◽  
Vol 49 (8) ◽  
pp. 3550-3553 ◽  
Author(s):  
Federico Pea ◽  
Pierluigi Viale ◽  
Daniela Damiani ◽  
Federica Pavan ◽  
Francesco Cristini ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Myeloid Leukemia ◽  
Steady State ◽  
Intravenous Infusion ◽  
Myeloid Leukemia ◽  
Continuous Intravenous Infusion ◽  
Pharmacokinetic Variability ◽  
Pharmacodynamic Profile ◽  
Neutropenic Patients ◽  
Acute Myeloid

ABSTRACT The pharmacokinetic-pharmacodynamic profile of a fixed 6-g daily continuous intravenous infusion of ceftazidime was assessed in 20 febrile neutropenic patients with acute myeloid leukemia. Mean steady-state ceftazidime concentrations averaging 40 mg/liter from day 2 on ensured maximized pharmacodynamic exposure (values close to four to five times the MIC breakpoint against Pseudomonas aeruginosa). However, large intra- and interindividual pharmacokinetic variability was documented throughout the study period.

scholarly journals Phase 1/2 study of DFP‐10917 administered by continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia

Cancer ◽  
2019 ◽  
Vol 125 (10) ◽  
pp. 1665-1673 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Elias J. Jabbour ◽  
Guillermo Garcia‐Manero ◽  
Tapan M. Kadia ◽  
Courtney D. DiNardo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Intravenous Infusion ◽  
Myeloid Leukemia ◽  
Phase 1 ◽  
Continuous Intravenous Infusion ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

Clinical Investigation of G-CSF-Priming Regimen in Treatment of Relapsing, Refractory and Senile Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4620-4620
Author(s):  
Zhen Cai ◽  
Xiaoyan Han ◽  
He Huang ◽  
Wanzhuo Xie ◽  
Weiyan Zheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Intravenous Infusion ◽  
Myeloid Leukemia ◽  
Clinical Investigation ◽  
Effective Rate ◽  
Control Group ◽  
Continuous Intravenous Infusion ◽  
Long Term Effects ◽  
Chi Square ◽  
Acute Myeloid

Abstract Objective:To evaluate the clinical outcome of granulocyte colony-stimulating factor (G-CSF) priming regimen in treatment of refractory, relapsing and senile aute myeloid leukemia. Materials and Methods:16 patients, 10 men and 6 women ranged in age from 15 to 78 years (median 48), with refractory, relapsing or senile acute myeloid leukemia were treated in our hospital between March 2002 and January 2004. All patients were diagnosed with MIC (morphologic, immunologic, cytogenetic) classification. The control group consists of 18 patients (12 men and 6 women, median age 48) with refractory, relapsing or senile acute myeloid leukemia treated in our hospital between 1999 and 2002. All of them were also diagnosed with MIC. All patients enrolled were treated with G-CSF-priming regimen consisting of low-dose cytosine arabinoside (Ara-C 10mg.m−2.12h−1, subcutaneously,day1–14), aclarubicin (Acla5-7mg.m−2.d−1, continuous intravenous infusion, day 1–8; or 10–14mg.m−2.d−1, continuous intravenous infusion, day1–4) or homoharringtonine (HHT 1mg.m−2.d−1, continuous intravenous infusion, day1–14), and concurrent use of G-CSF (100ug.m−2.12h−1, subcutaneously, day 1–14). In the course of chemotherapy, blood routine examinations were made every other day, and G-CSF was suspended while WBC>20x109/L. Chemotherapy intermission was 14–21 days. If two courses were of no effect, then the investigation was terminated. Patients in the control group received intensive chemotherapy with medium /high dosed Ara-C (1-3g.m−2.12h−1× 3–5d), combined with mitoxantrone or daunorubicin (DNR) or etoposide (vp-16).Statistics:Enumeration data was analyzed by Chi-square test. Results: All patients accomplished the chemotherapy, with no treatment related death. 9 of the 16 patients achieved complete remission. The CR rate was 56.25%, compared with 22.2% of the control group (Χ2=4.15, P<0.05). However, the total effective rate (68.75%) was not statistically higher than the control group (44.4%) (Χ2=2.03, P>0.05). Therapy related mortality (0.0%) was apparently decreased in priming group than in control group (38.9%) (Χ2=7.84, P<0.01). Conclusions:Our study shows that the priming regimen is effective and safe to refractory, relapsing, secondary or senile acute myeloid leukemia. Further studies are necessary to evaluate the long-term effects of this new therapeutic regimen in AML.

scholarly journals 1087. Fluoroquinolone Prophylaxis vs. No Bacterial Prophylaxis in Hospitalized Neutropenic Patients Undergoing Induction Chemotherapy for Acute Myeloid Leukemia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S386-S386
Author(s):  
Carley Buchanan ◽  
Derek N Bremmer ◽  
Anna Koget ◽  
Matthew Moffa ◽  
Nathan Shively ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Intervention Group ◽  
Additional Treatment ◽  
Newly Diagnosed ◽  
Post Intervention ◽  
Number Of Patients ◽  
Neutropenic Patients ◽  
Acute Myeloid

Abstract Background Despite evidence to support outpatient anti-pseudomonal fluoroquinolone (FQ) prophylaxis in neutropenic patients, limited data exist to support this for inpatients undergoing induction chemotherapy for acute myeloid leukemia (AML). At our institution, we implemented an initiative to replace FQ prophylaxis with a conditional order for an anti-pseudomonal β-lactam to be given if a fever occurred. Methods A retrospective chart review was conducted to analyze the outcome differences between patients receiving FQ prophylaxis (pre-intervention) and those who had a conditional order for an anti-pseudomonal β-lactam in place of FQ prophylaxis (post-intervention). Patients were included if they were ≥18 years of age and were newly diagnosed with AML undergoing induction chemotherapy. The primary outcome was 90-day all-cause mortality. Secondary outcomes included the number of patients requiring ICU admission and rate of bacteremic episodes caused by any pathogen and from a Gram-negative rod (GNR). Additionally, ciprofloxacin susceptibility of these pathogens was analyzed. Results There were 35 and 26 patients in the pre- and post-intervention groups, respectively. Between pre- and post-intervention groups, there was no difference in 90-day mortality (20.0% vs. 15.4%; P = 0.745) or ICU admissions (25.7% vs. 23.1%, P = 1), respectively. The rate of any bacteremic episode was similar between the pre- and post-intervention groups (51.4% vs. 65.4%; P = 0.307), but more patients in the post-intervention group developed GNR bacteremia (17.1% vs. 46.2%; P = 0.023). In the patients with GNR bacteremia, the number of ciprofloxacin nonsusceptible isolates was higher in the pre-intervention group (100% vs. 30.7%; P = 0.011). Conclusion Replacing FQ prophylaxis with a conditional order for an anti-pseudomonal β-lactam for inpatients newly diagnosed with AML receiving induction chemotherapy is a feasible option to decrease FQ exposure. Though increased episodes of GNR bacteremia were observed, there was no difference in total bacteremic episodes or clinical outcomes, and the improved ciprofloxacin susceptibility patterns will allow for an additional treatment option in this extremely vulnerable patient population. Disclosures All authors: No reported disclosures.

Micafungin Versus Voriconazole for Empirical Antifungal Therapy In Febrile Neutropenic Patients with Acute Myeloid Leukemia: A Randomized, Controlled Trial.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1062-1062
Author(s):  
Tatsuo Oyake ◽  
Shugo Kowata ◽  
Kazunori Murai ◽  
Shigeki Ito ◽  
Tomoaki Akagi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Antifungal Therapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Controlled Trial ◽  
End Point ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients ◽  
Acute Myeloid

Abstract Abstract 1062 Background: Invasive fungal infections (IFIs) incur significant morbidity and mortality among neutropenic patients after chemotherapy. The risk for these infections is related to the intensity and duration of neutropenia, and varies from 2% to 40%. Mortality rates associated with documented IFIs are considerable, reportedly ranging from 30% to 60%. Empirical antifungal therapy is the standard care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Several antifungal agents including voriconazole (VRCZ) or liposomal amphotericin B (L-AMB) have been studied as empirical therapy for febrile neutropenia (FN). However, limited data are available concerning the efficacy of micafungin (MCFG) in FN patients with acute myeloid leukemia (AML). Methods: We conducted a randomized, cooperative group, open-label trial comparing MCFG (150 mg once daily) with VRCZ (6 mg/kg twice on day 1 followed by 4 mg/kg twice daily) as first-line empirical antifungal treatment for 95 hospitalized FN patients with AML during induction or consolidation chemotherapy (MCFG, 49; VRCZ, 46). The efficacy end point was a favorable overall response, as determined by a five-component end point according to the criteria of Walsh et al (N Engl J Med 2004; 351: 1391). Results: At the time of enrolment, there were no significant differences in the demographics or baseline characteristics between the two groups. The mean treatment duration for MCFG and VRCZ was 10 and 9 days, respectively. The efficacy rates of MCFG and VRCZ were not significantly different (37.8% vs. 32.4%). The rates of breakthrough fungal infections (proven, probable and possible IFIs), successful treatment of baseline fungal infections, survival 7 days after end of therapy, and resolution of fever during neutropenia were similar in the two groups. However, premature discontinuation of therapy occurred less often in the MCFG group than in the VRCZ group (32.4% vs. 55.9%, P=0.0457*). In safety evaluation, there were fewer adverse events in the MCFG group than in the VRCZ group (27.0% vs. 64.7%, P=0.0013*). *: Chi square test Conclusions: MCFG was as effective as VRCZ, and better tolerated than VRCZ as empirical antifungal therapy in FN patients with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Disseminated Cutaneous Mycobacterium chelonae Infection in a Patient With Acute Myeloid Leukemia

2014 ◽  
Vol 1 (3) ◽  
Author(s):  
Anna Helena Roukens ◽  
Elodie J. Mendels ◽  
Nicolette L. Verbeet ◽  
Peter A. von dem Borne ◽  
Alina R. Nicolae-Cristea ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Manifestations ◽  
Diagnosis And Treatment ◽  
Mycobacterium Chelonae ◽  
Neutropenic Patients ◽  
Acute Myeloid

Abstract We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient who was treated with chemotherapy for acute myeloid leukemia. We discuss the clinical manifestations, diagnosis, and treatment of this unusual infection in neutropenic patients.

Dynamics of Procalcitonin and Bacteremia In Adult Acute Myeloid Leukemia with Chemotherapy-Induced Neutropenia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4378-4378
Author(s):  
Anne-Claire Gac ◽  
Jean-Jacques Parienti ◽  
Sylvain Chantepie ◽  
Roland Leclercq ◽  
Oumedaly Reman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bacterial Infections ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Short Term ◽  
Neutropenic Patients ◽  
Chemotherapy Induced Neutropenia ◽  
Sensitive Marker ◽  
Acute Myeloid

Abstract Abstract 4378 Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5 ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15. Disclosures: No relevant conflicts of interest to declare.

Phase I/II Study of Continuous-Infusion Troxacitabine in Refractory Acute Myeloid Leukemia

2007 ◽  
Vol 26 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Gail J. Roboz ◽  
Francis J. Giles ◽  
Ellen K. Ritchie ◽  
Sandra Allen-Bard ◽  
Tania J. Curcio ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Steady State ◽  
Continuous Infusion ◽  
Myeloid Leukemia ◽  
Serum Drug Concentration ◽  
Significant Activity ◽  
Platelet Recovery ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid ◽  
Refractory Aml

Purpose Troxacitabine is a non-natural nucleoside analog with unique structural and metabolic features. Bolus intravenous (IV) troxacitabine regimens have shown significant activity in patients with refractory acute myeloid leukemia (AML) and preclinical data suggest that administration via continuous infusion may result in enhanced antitumor activity. Patients and Methods Patients with refractory AML initially received troxacitabine 10.1 mg/m2 by continuous IV infusion (CIVI) for 48 hours. Infusion duration and daily dose were increased in subsequent patient cohorts. Results Forty-eight patients, median age 58 years (range, 21 to 81 years), were treated. Dose-limiting toxicities were mucositis and hand-foot syndrome, and 12.0 mg/m2/d for 5 days was established as the maximum-tolerated dose. Seven patients (15%) achieved complete remission (CR) or CR with incomplete platelet recovery (CRp), with a median survival among responders of 12 months. Steady-state concentrations of troxacitabine were found to be linearly and inversely proportionally related to calculated creatinine clearance at doses of 10.1 and 12.0 mg/m2/d. All patients responding to troxacitabine had steady-state serum drug concentration of more than approximately 80 ng/mL. In 27 patients achieving target troxacitabine plasma concentrations (ie, approximately 80 ng/mL) the CR + CRp rate was 26%. Conclusion Troxacitabine administered as a CIVI allows a significant increase in dose-intensity in comparison to IV bolus regimens, has antileukemic activity, and warrants additional investigation in patients with refractory AML. The recommended phase II study dose is 12.0 mg/m2 daily CIVI for 5 days.

scholarly journals EPCR Signaling Controls the Activity of Hematopoietic Stem Cells Independent of Coagulation Regulation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3263-3263
Author(s):  
Son Nguyen ◽  
Divij Verma ◽  
Claudine Graf ◽  
Shiri Gur-Cohen ◽  
Jennifer Royce ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Anticoagulant Function ◽  
Acute Myeloid

Abstract Background All mature blood cells are derived from multipotent hematopoietic stem cells (HSCs) which are activated to meet the demand of the host during inflammation and injury. The endothelial cell protein C receptor (EPCR) is a marker for primitivity and quiescence of HSCs but the relative contributions of EPCR signaling versus anticoagulant functions in HSC maintenance are incompletely defined. Aims We aimed to dissect functions of EPCR by studying anticoagulant and signaling function in HSC of EPCR C/S mice carrying a single intracellular point mutation abolishing normal trafficking of EPCR through endo-lysosomal compartments. We assessed the contributions of EPCR signaling to stem cell maintenance by analyzing HSC mobilization and leukemia progression. Methods We studied the frequency and cell cycle activity of bone marrow (BM) hematopoietic stem and progenitor cells (HSPC) by multicolor flow cytometry. Furthermore, we analyzed changes in hematopoiesis in steady state, after granulocyte colony stimulating factor (G-CSF)-induced mobilization, in the context of aging and in the context of leukemia, using the MLL-AF9-induced acute myeloid leukemia (AML) model. Results HSCs, lungs and isolated lung-derived smooth muscle cells of EPCR C/S mice showed protein expression levels and anticoagulant function indistinguishable from wildtype (WT). We found an increase of circulating HSCs in the peripheral blood of EPCR C/S mice compared to control under steady state conditions. Isolated HSC displayed diminished polarization of CDC42 and VLA-4 (α 4β 1 integrin) affinity to VCAM-1 in EPCR C/S versus strain-matched EPCR wt mice, indicating that EPCR signaling directly controls HSC retention via integrin affinity to the BM niche. In addition, we noticed a higher cell cycle activity in myeloid-restricted progenitors of EPCR C/S mice compared to control. G-CSF treatment led to increased mobilization of both BM neutrophils and HSCs into the peripheral blood of EPCR C/S mice compared to EPCR wt mice. A myeloid bias was also seen in serially transplanted aged mice, resulting in increased frequencies of myeloid-biased progenitors in the BM of EPCR C/S mice compared to control mice, accompanied by an increase of circulating neutrophils in the blood. Consistent with higher cell cycle activity of myeloid progenitors and an overall increase of myeloid-biased output in EPCR C/S mice, induction of AML by retroviral transduction of EPCR C/S BM cells with MLL-AF9-expressing retrovirus resulted in an increase of cell cycle activity of Lin - MLL-AF9 + leukemic BM blasts and a higher leukemic load in the peripheral blood of mice transplanted with MLL-AF9 + EPCR C/S BM compared to control. As a result, MLL-AF9 + EPCR C/S leukemia showed a more aggressive disease with shortened survival times compared to control. In contrast, chemotherapy of MLL-AF9 + EPCR C/S leukemia reduced leukemic load in the peripheral blood and decelerated disease progression. These data demonstrate that increased leukemia cell cycle activity conferred chemosensitivity. Conclusion With a site-specific EPCR mutant knock-in mouse, we here demonstrate that EPCR signaling and anticoagulant function can be separated. We provide direct evidence that EPCR signaling plays a crucial role in maintaining HSC retention via VLA-4 affinity to VCAM-1, controls cell cycle activity and myeloid output in normal, stress-induced, and malignant hematopoiesis with implications for therapeutic approaches in acute myeloid leukemia. Disclosures Ruf: MeruVasimmune: Other: Ownership Interest; ARCA bioscience: Consultancy, Patents & Royalties; ICONIC Therapeutics: Consultancy.

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