Clinical Safety of Long-Term Intravenous Itraconazole for the Treatment of Invasive Fungal Infection In Severely Ill Patients with Hematological Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4943-4943
Author(s):  
Yaping Xie ◽  
Shenxian Qian ◽  
Daquan Gao ◽  
Xilian Huang ◽  
Pengfei Shi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Hematological Malignancies ◽  
Liver Enzymes ◽  
Conflicts Of Interest ◽  
Oral Formulation ◽  
Clinical Safety ◽  
Severe Adverse Events

Abstract Abstract 4943 The clinical safety of intravenous itraconazole use exceeding 14 days is unknown. However, many cases need further treatment, but the absorption of itraconazole oral in severely ill patients is variable and unpredictable. Gastric acidity and food influence the absorption of oral formulation. The intravenous formulation, on the other hand, achieves adequate blood levels more rapidly and its bioavailability is predictable and invariable compared to the oral formulation. We performed this study to investigate the clinical safety of long-term intravenous itraconazole for the treatment of invasive fungal infection (IFI) in severely ill patients with hematological malignancies. 20 patients (median age, 70 years; range, 38–82 years) with hematological malignancies who had met the IFI inclusion criteria were enrolled. All the infection sites were the lung. These patients were given intravenous itraconazole for 14 days. There were significant effective but the lesions were not fully absorbed and no severe adverse events were found. So the long-term intravenous itraconazole therapy was enabled. Clinical efficacy and adverse events were recorded. Itraconazole 200 mg via intravenous infusion (administered over 1 hour) twice a day for 4 doses followed by 200 mg once a day until the lesions was fully absorbed. The treatment median time was 27(18-58) days. During this period, closely monitor changes in vital signs, chest CT, liver enzymes, renal function, electrocardiogram and electrolytes were assessed. We found that the patients achieved composite endpoints including survival, defervescence and undetectable lesions, except one patient died of primary disease - acute myeloid leukemia. Treatment-related adverse events were found in 7 patients (35%) during the study and none of them were severe adverse events. Such as hypokalemia (10.0%), gastrointestinal disorders (10.0%), elevation of liver enzymes (10.0%) and pleural effusion (5.0%). All the adverse events occurred during the first two weeks of the treatment and no significant exacerbation in the following days. In conclusion, long-term intravenous itraconazole therapy was effective for IFI and the drug-related adverse events have been shown to be generally predictable and manageable. Disclosures: No relevant conflicts of interest to declare.

Imatinib Long Term Effects (ILTE) Study: An International Study to Evaluate Long-Term Effects in CML Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2199-2199
Author(s):  
Dong-Wook Kim ◽  
Laura Antolini ◽  
François-Xavier Mahon ◽  
Francois Guilhot ◽  
Michael Deininger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Conflicts Of Interest ◽  
International Study ◽  
Imatinib Treatment ◽  
Long Term Effects ◽  
First Line ◽  
Serious Adverse Events ◽  
Second Cancers

Abstract Abstract 2199 Poster Board II-176 Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an independent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA) and Regione Lombardia. ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa, Middle East and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in CCyR after two years of imatinib treatment. Study endpoints were (a) survival, (b), serious adverse events (SAE, including second cancers), (c) toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, (d) loss of CCyR, and (e) development of PCR negativity. A total of 948 patients were enrolled, 88% of which met eligibility criteria after centers were visited and monitored. The median age of eligible patients was 51 (range 18-92) years; 59% of patients were males and the median follow-up was 4.0 years (excluding the first 2 years of treatment). As of Dec. 31 2008, 3255 person years were available for analysis. Twenty one deaths were observed (only 6 of them [28%] caused by relapsed CML), with a standardized rate of 0.6/100 person years and an observed/expected ratio of 0.7 (95% CI = 0.43-1.07, p=ns). A total of 138 SAE were recorded (rate 4.2/100 person years, most frequent type “heart failure”), with 19.5% being considered related to imatinib. Second cancers were documented in 29 patients (rate 0.9/100 person years), with an observed/expected ratio of 1.02. Among the 761 NSAE recorded (rate 23.4/100 person years) the most frequent types were cramps, asthenia,edema, skin fragility, diarrhea; 69% of them were considered related to imatinib. A total of 18 patients (2.2 %) discontinued imatinib because of toxicities during the period of observation. Forty patients lost CCyR, corresponding to a rate of 1.3/100 person years (1.0 in patients with imatinib as first-line treatment, 1.4 in patients who were treated with imatinib >6 months after diagnosis), with stable or increasing rates over time. Finally, 256 patients (36.0 %) developed durable (> 1 year) PCR negativity. In conclusion, this report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates similar to an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately 1/3 of cases. Follow-up and further analysis are ongoing. (Presented on behalf ofthe ILTE Investigators group) Disclosures: No relevant conflicts of interest to declare.

Safety and Efficacy of Fecal Microbiota Transplantation for Recurrent Clostridium Infection in Patients with Hematologic Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3599-3599
Author(s):  
Mehrdad Hefazi ◽  
Mrinal M Patnaik ◽  
William J Hogan ◽  
Mark R Litzow ◽  
Darrell S Pardi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Broad Spectrum ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Fecal Microbiota Transplantation ◽  
Hematologic Malignancies ◽  
Fecal Microbiota ◽  
High Risk Population ◽  
Safety And Efficacy ◽  
Increased Risk

Abstract Background: Patients with hematological malignancies are at an increased risk for developing both primary and recurrent Clostridium difficile Infection (RCDI) along with complications such as toxic mega colon and treatment failure likely due to underlying immunosuppression and frequent use of broad spectrum antibiotics that lead to altered gut microbiome. Fecal Microbiota Transplantation (FMT) is an effective treatment for RCDI (Brandt et. al; 2012). However, experience in patients with hematologic malignancies is sparse and most clinical trials exclude these patients due to potential complications. We report the largest case series to date from a single institution evaluating the safety and efficacy of FMT for RCDI in patients with hematologic malignancies. Methods: After IRB approval, a database of 452 RCDI patients treated with FMT between August 2012 and June 2016 was reviewed to identify those with an underlying hematologic malignancy. Data regarding demographics, hematologic disease, C. difficile history, treatments, and outcomes were retrospectively abstracted from the electronic medical record. Results: Sixteen patients (median age 74 years; male 50%) with known hematologic malignancies underwent FMT during the study period. The underlying diagnoses are outlined in Table 1. Five patients had received hematopoietic cell transplantation (3 allogeneic and 2 autologous) prior to FMT. Patients had a median of 4.5 (range 2-9) CDI episodes before FMT, and 4 of them had severe/severe-complicated CDI at some stage. Prior treatments included a median of 3 (range 1-5) standard vancomycin/metronidazole courses, median of 2 (range 0-4) vancomycin taper courses, fidaxomicin in 3 patients, and chronic vancomycin suppression in one patient. Diarrheal symptoms were in remission in all but 3 patients in the week before FMT. FMT was performed via colonoscopy in all patients. At the time of FMT, hematologic malignancies were in complete remission in 9 patients, stable on active treatment in 4, stable off treatment in 2, and relapsed awaiting treatment in 1 patient. Median time from last anti-neoplastic treatment (n = 14) and from last neutropenia (n = 8) to FMT were 10 (range 0-301) and 9.5 (0-68) months, respectively. One patient with hairy cell leukemia was still neutropenic and on prophylactic oral trimethoprim/sulfamethoxazole at the time of FMT. Five patients were on active immunosuppressive medications, including prednisone (n = 2), methotrexate (n = 2), sirolimus (n =1), and cyclosporine (n =1) for related comorbidities at the time of FMT (Table 2). At last follow up (median 12, range 0-32 months), 6 patients had active/relapsed hematological disease, 6 had received additional antineoplastic treatments, and 7 had received additional antibiotics. RCDI developed in two (12%) patients at 8 and 22 months post FMT secondary to exposure to broad spectrum antimicrobials. These patients were successfully treated with a second FMT and with metronidazole, respectively. Severe adverse events included death in one patient that occurred 3 days post FMT due to unexpected cardiac arrest and was deemed unrelated to the procedure. Another patient developed community-acquired pneumonia 15 days post FMT and was treated successfully with oral azithromycin. Minor adverse events within the first two weeks post FMT were noted in 6 (38%) patients (self-limited diarrhea in 3, fecal urgency in 2, abdominal cramps in 2, and constipation in one patient) (Table 3). Only one patient had persistent diarrhea shortly after FMT, with the cause attributed to underlying Crohn's disease. No complications related to the colonoscopy procedure were noted. Conclusion: FMT appears to be a safe and effective therapeutic option for RCDI in patients with hematological malignancies. Considering very few adverse events and particularly no infectious complications in our series, we conclude that immunosuppression should not preclude the use of FMT for treatment of RCDI in this high risk population. These results need prospective validation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Adverse Events Following Infusion of T Cells for Adoptive Immunotherapy: A 10 Year Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3212-3212
Author(s):  
Conrad Russell Y. Cruz ◽  
Patrick Hanley ◽  
Hao Liu ◽  
Vicky Torrano ◽  
Yu-Feng Lin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Safe Procedure ◽  
Cell Product ◽  
Increased Risk ◽  
Infusion Reactions ◽  
Severe Adverse Events

Abstract Abstract 3212 Poster Board III-149 Following administration of ex-vivo expanded T cells, the FDA currently recommends at least 4 hours of recipient monitoring to detect early infusion reactions. Recent catastrophic reactions to “first in man” biological agents have emphasized the importance of this rule for initial studies of new products, but its value for longer established agents is less evident. We have therefore reviewed the incidence and nature of infusion-related adverse events (AEs) associated with administration of ex-vivo expanded T cell products (antigen specific CTLs, allodepleted T cells, and genetically modified T cells) on Investigational New Drug (IND) studies in our center over the last decade. From 1998 to 2008, we infused 381 T cell products to 180 recipients who were enrolled on 18 such studies, receiving T cells targeting malignancies or post-transplant viral infections. The age of these recipients ranged from 9 months to 80 years. Cell doses were protocol specific and ranged from 104/kg up to 3 ×108/m2. Patients were premedicated with diphenhydramine (0.5-1mg/kg) and acetaminophen (10mg/kg up to a maximum of 625mg) prior to infusion. All cellular products were cryopreserved and administered intravenously over 1-15 minutes immediately after thawing. There were no Grade 3-4 infusion reactions during initial monitoring or 24 hour follow-up. Twenty four grade 1-2, non-severe adverse events (AEs) occurred in 21 infusions either during or immediately following infusion (up to 6 hours). The most common AEs were nausea and vomiting (10/24; 41.6%), most likely due to DMSO used in cryopreservation of T cell products, and hypotension (20.8%), attributable to diphenhydramine pre-medication. An additional 22 non-severe events within 24 hours of infusion were reported, the most common of which were fever (with negative blood cultures)/chills/constitutional symptoms (6/22; 27.3%) and nausea/vomiting (4/22; 18.2%) Overall, a total of 46 non-severe adverse events were noted within 24 hours of T cell product infusion (12.56%). A Fisher's exact analysis of all T cell product infusions grouped by patient age, patient ethnicity, or cell source revealed no association with increased risk. T cells from both allogeneic and autologous sources produced similar adverse events in terms of type, frequency, and severity, and allogeneic cells that were mismatched at > 2 HLA antigens had the same AEs as donor T cells matched at 5/6 or 6/6 HLA loci. We further analyzed the data using Poisson regression and the general estimating equation (GEE) model for correlated counts, to seek associations that may have been missed because AEs within a subject may not be statistically independent. By this analysis, we found decreased risks of adverse events in older patients (IRR 0.98; 95% CI 0.96-1.00; p=0.05), and increased risks of immediate (defined as occurring during the monitoring period) infusion-related events in patients reporting allergies (IRR 2.72; 95% CI 1.00-7.40; p=0.05). We thus conclude that infusion of the ex-vivo expanded T cell products used in these studies is a safe procedure associated with no severe reactions, that it is safe in the outpatient setting and that monitoring can be limited to an hour after infusion. As many of the AEs observed were due to diphenhydramine premedication, a lower dose (0.25mg/kg) of this agent may be preferred. Disclosures No relevant conflicts of interest to declare.

A Multicenter, Randomized, Open-Label Study to Evaluate Safety and Efficacy of Posaconazole Vs Fluconazole in the Prophylaxis of Invasive Fungal Infection in a Chinese Population

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4916-4916
Author(s):  
Shen Yang ◽  
Xiaojun Huang ◽  
Jianxiang Wang ◽  
Jie Jin ◽  
Jianda Hu ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Failure Rate ◽  
Invasive Fungal Infection ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Randomized Study ◽  
Treatment Phase ◽  
Clinical Failure ◽  
Open Label ◽  
Neutropenic Patients

Abstract Abstract 4916 Background Invasive fungal infection (IFI) is a common and fatal complication in neutropenic patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods In this multicenter, randomized study, we enrolled patients with persistent neutropenia resulting from chemotherapy for the treatment of AML and MDS. Prophylaxis with either posaconazole or fluconazole was given to the patients to compare the efficacy and safety of the 2 drugs. The treatment was given with each cycle of chemotherapy until the patient recovered from neutropenia and had complete remission, an IFI occurred, or until the patient had received a maximum of 12 weeks of treatment. The primary end point was the incidence of possible, proven, or probable diagnosis of IFI during the treatment phase in *the 2 groups; clinical failure rate, all-cause mortality, and time to first systemic antifungal treatment were secondary end points. Results A total of 252 patients were included in this study, and 7 patients were excluded due to withdrawal of informed consent or deviation of eligible criteria. Finally, 124 patients from the posaconazole group and 121 patients from the fluconazole group were included; and 234 patients (117 in each group) entered into statistical analysis, respectively. The incidence of proven, probable, and possible IFI was 9.4% (11/117) and 22.2% (26/117) in the posaconazole and fluconazole groups, respectively (P = 0.0114). The clinical failure rate was lower in the posaconazole group (31.6% [95% CI: 23.3–40.9], 37/117) than in the fluconazole group (41.88% [95% CI: 32.8–51.4], 49/117); however, statistical significance was not reached (P = 0.168). The patients receiving posaconazole had a later onset of first systematic antifungal therapy than those receiving fluconazole (P = 0.0139). The most common clinical adverse reactions were liver function abnormalities, with 11 cases (9.4%) in the posaconazole group and 6 cases (5.1%) in the fluconazole group (P = 0.221). Conclusions Posaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic patients with AML and MDS undergoing chemotherapy and is well tolerated during long-term use. (ClinicalTrials.gov number, NCT00811928) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Two Cases of Long-Term Control of Metastatic Colorectal Cancer via FTD/TPI plus Bevacizumab in Elderly Patients

2018 ◽  
Vol 11 (3) ◽  
pp. 800-805 ◽  
Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Tatsunari Fukuoka ◽  
Yasuhito Iseki ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Intensive Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Severe Adverse Events ◽  
Third Line ◽  
Third Line Treatment ◽  
First Line Treatment

With advances in new cytotoxic drugs and molecular-targeted drugs, the prognosis of patients with metastatic colorectal cancer (mCRC) has improved. However, physicians often hesitate to administer intensive standard regimens to elderly patients with mCRC. Recently, first-line regimens that are effective in and well-tolerated by patients who are not eligible for intensive chemotherapy have been established. However, the therapeutic strategies to adopt after the failure of first-line treatment for patients who are not eligible for intensive chemotherapy remain unclear. We herein report two cases of long-term control of mCRC via FTD/TPI+bevacizumab (Bmab) as second- or third-line treatment in elderly patients without severe adverse events. In case 1, first-line treatment with Tegafur-Uracil, which is a prodrug of 5-FU, caused disease progression in a short period after the initiation of chemotherapy. In case 2, intensive first-line treatment caused severe adverse events, and treatment was discontinued. However, in both cases, disease control was obtained for a long time without severe adverse events by subsequent treatment with FTD/TPI+Bmab. The success in these present cases indicates that FTD/TPI+Bmab as a second- or third-line treatment is a therapeutic option for elderly patients with mCRC who are not eligible for intensive chemotherapy, even after failure of treatment with 5-FU.

scholarly journals Tolerability of Omalizumab in Asthma as a Major Compliance Factor: 10-Year Follow Up

2018 ◽  
Vol 6 (10) ◽  
pp. 1839-1844 ◽  
Author(s):  
Mona Al-Ahmad ◽  
Jasmina Nurkic ◽  
Ahmed Maher ◽  
Nermina Arifhodzic ◽  
Edin Jusufovic
Keyword(s):  
Adverse Events ◽  
Treatment Efficacy ◽  
Real Life ◽  
Drop Out ◽  
Uncontrolled Asthma ◽  
Increased Risk ◽  
Asthma Patients ◽  
Severe Adverse Events

BACKGROUND: There is a lack of data related to real life, long-term safety, tolerability and compliance of omalizumab treatment in asthma patients beyond 6 years. AIM: Study aimed to assess safety, tolerability, compliance and all reasons for treatment discontinuation during 10 years on omalizumab. SUBJECT AND METHODS: This is a retrospective, observational study of uncontrolled asthma patients receiving omalizumab for the last 10 years. All data were collected from patients’ files (demographics, adverse events, comorbidities, compliance index, reasons for discontinuation of omalizumab). Reactions to omalizumab were classified as local and systemic, and their severity as mild, moderate or severe. Reactions were either immediate (minutes to hours after drug administration) or delayed (after days). Compliance to omalizumab, defined as Compliance index (CI), was calculated by comparing milligrams of given to milligrams of prescribed dose/ per year. RESULTS: Out of 35 patients receiving omalizumab, 15 drop out at different time points mostly due to treatment efficacy or appearance of new comorbidities. Patients who continue for the next ten years had mild to moderate adverse events related to omalizumab. There was no increased risk of severe adverse events during 10 years on omalizumab. Patient’s treatment tolerability, despite mild to moderate adverse events, is in favour of compliance. CONCLUSION: Compliance with omalizumab mildly decreased over 10 years but was not affected by severe adverse events of treatment or new comorbidities. Although, omalizumab is safe medicine appearance of new comorbidities has to be closely followed up.

Clinical Use of Caspofungin in Immunocompromised Children: A Multicenter Survey.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5066-5066
Author(s):  
Thomas Lehrnbecher ◽  
Andishe Attarbaschi ◽  
Friedhelm Schuster ◽  
Nadine Herzog ◽  
Lorenz Grigull ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Antifungal Agents ◽  
Pediatric Patients ◽  
Bone Marrow Failure ◽  
Single Agent ◽  
Clinical Use ◽  
Retrospective Survey ◽  
Multicenter Survey

Abstract Background : Caspofungin (CAS) is a novel echinocandin, which is approved for several antifungal indications in adults. Although the compound is not licensed in pediatric patients (pts), it is being used in children with refractory infections or intolerance to standard antifungal agents. Methods: We conducted a multicenter retrospective survey to obtain data on clinical use, safety, and outcome in immunocompromised pediatric pts who received therapy with CAS. Results : The survey identified 71 immunocompromised children and adolescents [mean age (range) 11.4 years (5 months –26 years)]. Out of the 29 females and 42 males, 53 suffered from hematological malignancies, 10 from bone marrow failure syndromes, 3 from solid tumors, 2 from congenital immunodeficiency, and 3 from non-malignant hematological disorders. Forty-two pts (59%) had undergone allogeneic blood stem cell transplantation, and 36 pts (51%) had an ANC of less than 500/μL at baseline. CAS was administered for proven (n=18), probable (15), and possible (20) invasive fungal infection, or as empirical antifungal treatment (18). All but one pt had received prior systemic antifungal therapy with amphotericin B (52) and/or triazoles (41). The 71 pts received CAS for a mean duration of 43.5 days (range, 2–218) as single agent (22) or in combination with other antifungal agents (49). The mean maintenance dosage of CAS was 1.2 mg/kg (range, 0.4–2.9) or 34.8 mg/msqu (range, 16.3–57.5). In none of the pts, CAS was discontinued prematurely due to clinical or laboratory adverse events. Clinical adverse events were described in 35 children (49%), mostly fever (28), nausea and vomiting (18), diarrhea (8), and headache (5). Increases in hepatic or renal function parameters were frequent in these pts that received multiple other therapeutic compounds. Whereas at the end of treatment (EOT), mean GPT and GOT were slightly elevated (from 41 at baseline to 61 U/L at EOT; p=0.002 and from 29 to 80 U/L, p=0.001, respectively), mean serum creatinine, bilirubin, and alkaline phosphatase values were not different from baseline. Complete responses, partial responses, or stabilization were observed in 4/8/3 of 18 evaluable pts with proven, in 4/2/3 of 13 pts with probable, and in 3/8/2 of 15 pts with possible invasive fungal infection. Of 16 evaluable pts who received CAS empirically therapy, 10 successfully completed therapy. Overall survival was 74% at EOT and 67% at three months post EOT (65 and 60 evaluable pts, respectively). Conclusions: The data of this retrospective survey show that CAS displays acceptable safety and tolerance and may have useful antifungal efficacy for second line treatment of severely immunocompromised pediatric patients.

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