Comparable Efficacy and Safety with Voriconazole or Posaconazole as Primary Antifungal Prophylaxis in Acute Myeloid Leukemia (AML) Patients Receiving Induction Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2059-2059
Author(s):  
Gene A Wetzstein ◽  
Timothy J. George ◽  
Mahsa Sharifi ◽  
Van D Hoang ◽  
Viet Q Ho ◽  
...  
Keyword(s):  
High Risk ◽  
Mortality Rate ◽  
Median Time ◽  
Induction Chemotherapy ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Comparable Efficacy ◽  
High Risk Population ◽  
Prophylactic Therapy ◽  
Efficacy And Safety

Abstract Abstract 2059 Poster Board II-36 Background: Patients with prolonged neutropenia are at significant risk for invasive fungal infections (IFI's). The incidence of proven or probable IFI's range from 5-24% in patients treated with AML. Furthermore, the mortality rate in this high-risk population has been reported to be as high as 86% for invasive pulmonary aspergillosis. Given the high mortality rate associated with IFI's and our inability to reliably diagnose active cases, prophylactic therapy has emerged as the preferred approach in this high risk patient population. Recently, Cornely et al. conducted a large, prospective randomized trial evaluating prophylactic posaconazole vs. fluconazole or itraconazole in AML/MDS patients receiving induction chemotherapy. Posaconazole (P) was found to be superior to the standard azoles with respect to the incidence of proven or probable IFI's and demonstrated an overall survival benefit. Given these findings, our institution adopted P as primary antifungal (AF) prophylaxis in this setting. Previously our standard prophylactic approach was voriconazole (V) which has a similar spectrum of activity and is available in an oral and IV formulation in contrast to P which is only available orally. There does not appear to be any comparative published literature to date between these two extended-spectrum azoles in the prophylactic setting. We report herein on the efficacy and safety of voriconazole and posaconazole as primary AF prophylaxis between January 2005 and June 2008. Methods: Patients > 18 yo receiving AML/MDS induction chemotherapy without documentation of IFI were included in this retrospective analysis. The voriconazole group received 400mg PO BID × 1 day, then 200mg PO BID. The posaconazole group received 200 mg PO TID with meals. Therapy was initiated on the first day of chemotherapy or 24 hrs post anthracycline and continued until neutrophil recovery, initiation of empiric AF therapy, occurrence of proven/probable IFI, or adverse event (AE) requiring discontinuation of therapy. Proven/probable IFI was defined in accordance with the EORTC/MSG criteria. Results: 195 patients were evaluable (N=129 V; N=66 P). Baseline characteristics were similar between the two groups with respect to age, sex, diagnosis, cytogenetics, disease status, days of neutropenia, and utilization of growth factors. Median time on prophylaxis was 16 (range: 4-44) and 14 (range: 3-69) days, respectively for P and V. Nine pts (7%; 95% CI (3-13%)) developed proven/probable IFI (6 non-albicans candida, 2 fusarium, 1 zygo) in the V group versus four (6%; 95% CI (2-15%)) IFIs ( 2 trichosporon, 1 fusarium, 1 scedosporium) in the P group. Median time of prophylactic therapy to diagnosis of IFI was 29 days for P vs 25 days for V, respectively. Eight pts (6%) discontinued V therapy because of AE's (4 hallucinations, 1 rash, 2 LFT elevation, 1 torsades) vs five pts (7.5%) for P (3 LFT elevation, 1 vomiting, 1 rash). Conclusion: In the present analysis, we report the comparable efficacy and safety of voriconazole and posaconazole as primary AF prophylaxis in high risk AML/MDS patients receiving induction chemotherapy. There were no differences in the incidence of proven/probable IFI's, time to IFI, time to empiric AF therapy, or AE's requiring discontinuation of therapy. Disclosures: Wetzstein: Pfizer Pharmaceuticals: Honoraria; Schering-Plough Pharmaceuticals: Honoraria. Off Label Use: Voriconazole as primary antifungal prophylaxis therapy in AML patients receiving induction chemotherapy.

Is Antifungal Prophylaxis Useful In Stem Cell Transplantation (SCT) During Hospitalization?.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4541-4541
Author(s):  
Giuseppe Irrera ◽  
Messina Giuseppe ◽  
Giuseppe Console ◽  
Massimo Martino ◽  
Cuzzola Maria ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Mucosal Damage ◽  
Invasive Disease ◽  
Secondary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
High Risk Patients ◽  
Risk Patients

Abstract Abstract 4541 Introduction: Limited data demonstrate to what extent preventing fungal exposures is effective in preventing infection and disease. Further studies are needed to determine the optimal duration of fluconazole prophylaxis in allogeneic recipients to prevent invasive disease with fluconazole-susceptible Candida species during neutropenia. Oral, nonabsorbable antifungal drugs might reduce superficial colonization and control local mucosal candidiasis, but have not been demonstrated to reduce invasive candidiasis. Anti-fungal prophylaxis is recommended in a subpopulation of autologous recipients with underlying hematologic malignancies with prolonged neutropenia and mucosal damage. Methods: This is a retrospective study of 1007 SCT performed in our center between 1992 and 2009 in 809 consecutive patients, irrespective of diagnosis. HEPA filter and environmental monitoring (air, water, surfaces) are attributes of our transplant center. Results: The main characteristics of the patients are reported in Table 1. Systemic prophylaxis was used according to the guidelines (Table 2): fluconazole in the nineties, then itraconazole and from 2004 was either abolished or substituted with non-adsorbable prophylaxis in transplants with standard risk. Secondary prophylaxis was prescribed for high risk patients (with infectious fungal history, suggestive iconography, positive fungal biomarker). In 17 years our Center has never been colonized by mould. Only 3 probable aspergillosis infections and 4 proven fungal infections (fusarium, mucor and 2 aspergillosis) were diagnosed, all in allogeneic patients (2 haplotipical, 1 singenic, 1 sibiling, 1 MUD and 2 mismatched), resulting in death in all cases. No infection was documented in autologous setting, while the infection rate in allogenic setting was 3.6% with an incidence rate of 1.1 infection per 10000 transplants/year. These results are significantly lower than published reports. Conclusion: Systemic antifungal prophylaxis should not be performed in autologous SCT patients. The abuse of systemic prophylaxis targeting yeasts has influenced the change of epidemiology in the transplant setting with prevalence of mould infections. The identification of high risk patients is useful to select patients for systemic antifungal or secondary prophylaxis to reducing overtreatment, incidence of resistant strains and costs. Disclosures: No relevant conflicts of interest to declare.

First results of prophylaxis for bacterial and fungal infections in pediatric patients with high-risk acute lymphocytic leukemia (ALL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10065-10065
Author(s):  
Annick Beaugrand ◽  
Renato Guedes Oliveira ◽  
Ethel Gorender ◽  
Renato Melaragno ◽  
Sidnei Epelman
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Intensive Therapy ◽  
Antifungal Prophylaxis ◽  
Lymphocytic Leukemia ◽  
Morbidity And Mortality ◽  
Published Data ◽  
Intensive Chemotherapy ◽  
First Results ◽  
Antibacterial And Antifungal

10065 Background: Bacterial and invasive fungal infections remain a major contributor to treatment related morbidity and mortality in cancer patients. It has been published data of potential prevention; in immunocompromised hosts derive primarily from adult studies. However, children differ from adults in terms of the infections types as they develop or manifest, as well as their metabolism of treatment agents. From April 2010 to January 2011, 6 ALL patients received 35 intensive chemotherapy cycles during the first 6 months after diagnosis, 2 died due to infection. Methods: From April 2011 to January 2012, a prospective analysis in 8 high risk ALL patients ( BFM criteria) after 31 cycles of intensive chemotherapy were performed during the first 6 months of treatment followed by antibacterial and antifungal prophylaxis. Drugs are: ciprophloxacin 1000mg per day when weight highest than 30 kg and 500mg per day when lower weigh and fluconazole 100mg per day for the lower weigh and 150mg for the higher. All patient received granulocyte colony-stimulating factor after each cycles until complete neutrophils recovery. Results: In 20/31 cycles, hospitalization was needed, due to febrile neutropenia. Diarrhea, sepsis and renal failure were other reasons for hospitalization. Platelet transfusions and blood transfusions were performed in 12 and 9 hospitalization respectively. The majority of proven infections (n=7) were bacterial, Gram negative (Pseudomonas aeruginosa and Klebsiella spp), Gram positive, Candida (1 cycle). Hospitalization time was between 2 and 25 days (median time 10 days). In 4 cycles, intensive care unit was needed. No death occurred. Conclusions: Bacterial and fungal infections continue to be a leading cause of morbidity and mortality in children receiving intensive therapy. Pharmacologic prophylaxis can contribute to decrease mortality due to infection in this population.

Benefit of Anti-Infectious Prophylaxis in Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Receiving Frontline “Targeted Therapy”.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2858-2858 ◽  
Author(s):  
Nitin Jain ◽  
Gloria N. Mattiuzzi ◽  
Jorge Cortes ◽  
Jennifer Cassat ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapy ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Intensive Chemotherapy ◽  
Standard Chemotherapy ◽  
Antibacterial And Antifungal ◽  
Acute Myeloid

Abstract Background Patients with high risk (HR) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have significant toxicities such as mucositis, protracted neutropenia and severe infections when treated with standard chemotherapy. This had led to the development of ‘less intense’ chemotherapy (targeted therapy, TT). These treatments are expected to produce less toxicities, especially less immunosuppression. Antibiotic and antifungal prophylaxis are routinely given to patients undergoing intensive chemotherapy. It is not clear if the same strategy should be used for patients receiving less intensive chemotherapy. The objective of this study is to evaluate the outcome of patients receiving TT according to the use of antimicrobial prophylaxis. Methods We retrospectively reviewed the medical records of patients with AML and HR MDS that received TT as induction therapy from January 2000 to July 2007 at our institution. Baseline characteristics and antibiotic usage was recorded. All courses of TT received from start of therapy until outcome (response or failure) was assessed were evaluated, and infections or death occurring during any of these courses constituted an event. Results 225 patients received TT [decitabine or azacitidine n = 137 (61%); miscellaneous (tipifarnib, PKC412, imatinib, SAHA, and others) n=88 (39%)] for a total of 583 courses (median course per patient = 2). Median age was 72 years (range 13–89), 60% were male, 95% had Zubroad performance status ≤ 2 and 28% were neutropenic at the start of TT. None of the patients were placed in HEPA-filtered rooms (‘protected environment’) at any time. Each course of therapy was grouped into 1 of 4 groups based on the strategy use for infectious prophylaxis (table 1). Clinically documented infections and FUO were the most frequent type of infection reported in all the groups, followed by bacterial infections. Fungal infections were infrequent (total 5; group 1 = 1; group 2 = 2, group 3 = 2). There was no significant difference in the number of infectious episodes per course between the groups that received both antibacterial and antifungal prophylaxis vs. those who received no prophylaxis (p= 0.984). However, mortality was significantly higher during courses of TT administered without prophylaxis (p= 0.005). Conclusions As opposed to standard chemotherapy, fungal infections are infrequent in the patients treated with TT. Mortality is significantly higher in patients who did not receive any anti-microbial prophylaxis. The use of antibacterial and antifungal prophylaxis should be considered in patients receiving TT. Table 1: Groups based on antimicrobial strategy Strategy Strategy No. of courses No. of infectious episodes (%) No. of death (%) * p=0.984; # p=0.005 No prophylaxis 202 45 (22%) * 12 (5.94%) # Both bacterial and fungal prophylaxis 171 38 (18%) * 1 (0.58%) # Only bacterial prophylaxis 206 31 (15%) 6 (2.91%) Only fungal prophylaxis 4 0 (0%) 0 (0%)

Caspofungin Primary Antifungal Prophylaxis in Acute Leukemia Patients During Induction Therapy: Results of a Prospective Phase II Multicentric Study (ProfilC Study).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1638-1638
Author(s):  
Chiara Cattaneo ◽  
Simona Monte ◽  
Alessandra Algarotti ◽  
Ernesta Audisio ◽  
Erika Borlenghi ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Induction Therapy ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Prophylaxis ◽  
Blood Levels ◽  
Predictive Tool ◽  
Who Grade ◽  
Multicentric Study

Abstract Abstract 1638 Poster Board I-664 Background The need for antifungal prophylaxis in acute leukemia (AL) is a very debated topic, considering its potential of inducing resistant strains and of impairing detection of Aspergillus antigen as well as cost-efficacy balance. Targeted prophylaxis, focused on patients (pts) with high risk diseases (e.g. AL during induction therapy), seems to be the most promising strategy. Caspofungin is a well-tolerated echinocandin, with a different mechanism of action with respect to azoles and amphotericin B. Pentraxin 3 (PTX3) belongs to the superfamily of pentraxins acute-phase reactants and may play a protective role against Aspergillus spp (Garlanda et al, Nature 2002). Aims To determine the incidence of invasive fungal infections (IFIs) and invasive aspergillosis (IA), the efficacy and safety of caspofungin as primary antifungal prophylaxis during AL induction and to evaluate PTX3 levels as in vivo predictive tool for IFI development. Patients and Methods From Jan-07 to Jan-09, the incidence of IFIs and IA during induction was evaluated among all pts with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) registered in NILG (Northern Italy Leukemia Group) protocols. Ninety-three pts entered the prospective ProfilC protocol and received Caspofungin prophylaxis (70 mg i.v. d1, then 50 mg i.v./d till leukemia remission). ProfilC epidemiological data were compared with those observed among 82 pts not assigned to ProfilC and treated according to the standard prophylactic (SP) policy adopted by each center (67 itraconazole, 10 fluconazole, 1 posaconazole, 4 no prophylaxis). PTX3 blood levels could be evaluated in 90 pts. Results Considering all 175 pts, M/F ratio was 103/72, median age was 50 (range 18-73); AML/ALL ratio was 138/37. Overall 32 IFIs (18.3%) were observed, 10 probable/proven (5.7%) (8 IA, 1 Candida spp and 1 G. capitatum bacteremias) and 22 possible (12.6%) according to EORTC/MSG criteria. IFIs (probable/proven and possible) were more frequent in AML (6.5% and 14.5%) than ALL (2.7% and 5.4%). Probable/proven IAs were not seen in ALL. The incidence of probable/proven or possible IFIs between ProfilC pts and those treated with SP was 7.5% and 9.7% vs 3.7% and 15.9%, respectively. Specifically, probable/proven or possible IAs were 5.4% and 8.6% in ProfilC group and 3.7% and 14.6% in SP group, respectively. These data show a lower, albeit not statistically significantly, incidence of IFI and IA in ProfilC pts. Fifteen out of the 175 (8.6%) pts died (ProfilC: 9.7%, SP: 7.3%, p=ns) with only one death due to IFI (G. capitatum sepsis). None of the 8 pts with IA died. Five pts experienced WHO grade >2 toxicity (3 hepatic, 1 skin, 1 hepatic and renal), 3 receiving Caspofungin and 2 itraconazole. One of the 5 pts died (itraconazole) of hepato-renal failure. A trend towards an association between lower PTX3 levels and IFI development was shown, since 13.8% of pts with PTX3 levels >10 ng/ml had IFI (probable: 3.4%), compared to 27.8% of those with '10 ng/ml (probable 8.2%). Conclusions Anti-Aspergillus oriented prophylaxis in AL pts was standard policy at most NILG centers. The incidence and letality of probable/proven IFIs and IA were lower than expected and reported by others. Given this epidemiological scenario, the superiority of one drug with respect to others is difficult to demonstrate. Caspofungin was well tolerated during induction and was at least as effective as other prophylactic agents. It may be particularly suited for AL pts with impaired intestinal absorption. High levels of PTX3 (>10 ng/ml) could be protective against IFI/IA, suggesting that PTX3 could be used to identify a very high risk pts population in which an intensified strategy of prophylaxis may be worth testing. Disclosures Off Label Use: Caspofungin as antifungal prophylaxis. Rossi:Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees.

Bortezomib, Bendamustine, and Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma: Encouraging Activity in the Phase 2 VERTICAL Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 933-933 ◽  
Author(s):  
Nathan Fowler ◽  
Brad S Kahl ◽  
Peter Rosen ◽  
Jeffrey Matous ◽  
Amanda Cashen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Clin Oncol ◽  
Board Of Directors ◽  
Research Funding ◽  
High Risk Population ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Advisory Committees ◽  
Grade 3

Abstract Abstract 933 Follicular lymphoma (FL) is an incurable, indolent B-cell non-Hodgkin lymphoma. Although survival has improved with the introduction of rituximab (Rituxan®, R), relapse is inevitable and new therapies are needed. Bortezomib (Velcade®, V) plus rituximab is active in relapsed or refractory (rel/ref) FL (de Vos et al, ASH 2006). Bendamustine (Treanda®, B) plus R has also shown activity in rel/ref FL (Robinson et al, J Clin Oncol 2008), and V has been safely combined with B in patients (pts) with advanced multiple myeloma (Fenk et al, Leuk Lymph 2007). The single-arm, multicenter, phase 2 VERTICAL study was conducted to determine the efficacy and safety of V and R in combination with B (VBR) in pts with rel/ref FL. Here we report preliminary phase 2 efficacy and safety findings from pts treated with VBR at doses determined in the dose-escalation phase of this study (Matous et al, ASCO 2009). Pts with rel/ref FL who had received ≥4 prior doses of R (no prior V or B), and had ≥1 measurable tumor mass, no active central nervous system lymphoma, Karnofsky Performance Status (KPS) ≥50%, adequate hematologic, renal, and hepatic function, and no grade ≥2 peripheral neuropathy (PN) were eligible. Pts could receive up to five 35-d cycles of V 1.6 mg/m2 (d 1, 8, 15, 22), B 90 mg/m2 (d 1, 2), and R 375 mg/m2 (d 1, 8, 15, 22, cycle 1; d 1, cycles 2–5). Response was assessed by the investigator using International Working Group criteria (Cheson et al, J Clin Oncol 2007). Adverse events (AEs) were graded using the CTCAE v3.0, and by laboratory assessment of hematologic toxicity. Sixty-three pts received VBR; median age was 58 years, 63% were male and 25% had KPS ≤80%. At diagnosis, 47% had grade 1, 26% grade 2, and 8% grade 3 histology, and 18% unknown histology; 35% had high-risk Follicular Lymphoma International Prognostic Index score. Pts had received a median of 2 prior therapies (range 1–11), and 39% were refractory to their last prior rituximab-containing therapy. The median time from diagnosis was 48 months. As of data cut-off (14 Aug 2009), pts had received a median of 3 cycles (range 1–5); 29 pts remain on therapy and 10 have completed treatment. In the 49 pts with at least one post baseline response assessment, to date, the overall best response rate was 84%; 23 (47%) pts achieved a complete response (CR) and 18 (37%) a partial response (PR). VBR was generally well tolerated, with manageable toxicities. The most common treatment-related AEs were primarily grade 1 and 2 and included nausea (79%; 3% grade 3), fatigue (65%; 10% grade 3), diarrhea (57%; 3% grade 3), and vomiting (44%; 5% grade 3). Other non-hematologic grade 3/4 AEs that occurred in more than one pt included syncope (n=2; 3%) and PN (see below). Grade 3/4 neutropenia, thrombocytopenia, and anemia were seen in 25%, 6%, and 3% of pts, respectively. Treatment-related serious AEs were reported in 17 (27%) pts, including 3 (5%) with febrile neutropenia and 1 (2%) with grade 3 herpes zoster who did not receive antiviral prophylaxis and discontinued therapy. Of the 17 (27%) pts with treatment-related PN, only 4 (6%) had grade 3 (2 discontinued therapy; no grade 4); PN has resolved in 5 (29%) pts to date. There was one on-study death (cardiac arrest) that was considered treatment-related. Additional follow-up is required to assess long-term outcomes, including progression-free and overall survival. VBR is active in this heavily pre-treated, high-risk population, with high CR rates, and was generally well tolerated. Efficacy and safety data will be updated and reported at ASH. Disclosures: Fowler: Millennium Pharmaceuticals, Inc.: Research Funding. Kahl:Milllennium: Consultancy, Research Funding; Cephalon: Consultancy, Research Funding. Rosen:Biogen Idec: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Southern California Lymphoma Group, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen : Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Tower Cancer Research Foundation: Employment. Matous:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cephalon: Membership on an entity's Board of Directors or advisory committees. Amin:Millennium Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncotype DX: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Williams:Milllennium: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Cephalon: Research Funding. Smith:Genentech: Membership on an entity's Board of Directors or advisory committees; Cephalon: Membership on an entity's Board of Directors or advisory committees. Shi:Millennium Pharmaceuticals, Inc.: Employment. Parasuraman:Milllennium: Employment. Cheson:Millennium Pharmaceuticals, Inc.: Consultancy, Speakers Bureau; Cephalon: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau.

Evaluation for the Need of Antifungal Prophylaxis In High Risk Hematologic Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4547-4547
Author(s):  
Olga Pérez ◽  
Manuela Aguilar ◽  
Almudena Martín ◽  
Jose Falantes ◽  
Isabel Montero ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem

Abstract Abstract 4547 Background Fungal infections remain a vital threat to the immunocompromised patient. Due to the high mortality rate of invasive mycoses, antifungal prophylaxis and prevention appear appropriate in some settings. Patients (pts) with prolonged and severe neutropenia or recipients of allogeneic hematopoietic stem cell transplantation (HSCT) appear to be at high risk for filamentous fungal infections, which are associated with low survival rates. However, there is no consensus on the optimal prophylaxis, eligible patients or its effectiveness and clinical impact. Objective To analyze the need for antifungal prophylaxis in Acute Leukemia patients receiving chemotherapy and the effectiveness of fluconazol, followed by posaconazol if GVHD developed, in recipients of allo-HSCT as antifungal prophylaxis. Methods and patients Period: from june’07 through june’09. Acute leukemia adult patients receiving chemotherapy as induction or re-induction therapy did not received primary antifungal prophylaxis. Recipientes of Allo-HSCT received 400 mg/d of fluconazole until discharge followed by 200 mg/8h of posaconazole if graft-versus-host disease (GVHD) developed, until its resolution. Patients received secondary antifungal prophylaxis according to their IFI. There were 77 pts who presented 218 episodes of post-chemotherapy neutropenia (80 in ALL and 138 in AML), 207 received no antifungal prophylaxis. On the other hand, we analyzed 40 consecutive Allo-HSCT adult recipients with an average age of 39 years (15-65) followed as in-patient and out-patient basis during a mean period of 18 months (3-24). Standard myeloablative or reduced intensity conditioning schemes were used and donors were HLA-identical sibling (27), unrelated donor (8) and umbilical cord blood (5). Diagnoses: AML (21), ALL (10), NHL (3), MDS (2), CML (2), HL (1) and AAS (1). The GVHD prophylaxis was according to standard protocols with MTX and CsP/MMF or standard umbilical cord blood protocols. Non-normal distribution data were expressed as median values (range). Chi-square test or Fisher exact test were used to compare differences between groups of categorical data. Differences were considered statistically significant for p-values < 0.05. All statistical analyses were performed using SPSS 16.0 software (Chicago, IL). Results Acute leukemia patients: There were 8 proved or probable fungal infections (EORTC/MSG consensus), with an incidence of 3.6%. The incidence of IFI in the whole induction AML group was 2.4%, (6.9% in the consolidation AML group, 25% in the re-induction AML group) and 5.2% in induction LLA and no case (0%) in the re-induction ALL group. As etiology, Aspergillus Fumigatus (1), Aspergillus spp (4), Candida tropicalis (1) and Candida spp (2). There were 3 deaths caused by IFI (37.5% of IFI); two of them in the re-induction AML group. Allogenic hematopoietic stem cell transplantation recipients: 33 patients received fluconazole (82.5%) and 4 pts (10%) fluconazole followed by posaconazole. Other 3 received posaconazole (2) or voriconazole 200 mg/12 hours (1) as secondary prophylaxis since the conditioning. There were 7 cases of IFI (incidence of 17.5%), 3 proved IFIs and 4 probable IFIs. As etiology, Aspergillus Fumigatus (2), Aspergillus spp (4) and Candida albicans (1). Six patients had received fluconazole and one (candidiasis), fluconazole and posaconazole. The mortality attributable to IFI were 4 cases (57% of IFI). There was no IFI in the group of 9 pts without GVHD and all IFIs occurred in patients treated for GVHD. Conclusions 1) Patients in re-induction of AML may require an effective prophylaxis against fungal infections, but not AML during induction or ALL in any situation. 2) The prophylaxis regimen studied in allogenic HSCT recipients was effective in preventing IFIs in patients without GVHD but not in patients with GVHD, particularly in the case of filamentous fungi. 3) The overall incidence of IFI in allo-HSCT was similar to that reported in other series of high risk and mortality from IFI similar to that described in recent years. 4) Patients with GVHD require more effective antifungal prophylaxis regimens and are candidates for clinical trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcomes of Antifungal Prophylaxis in High-Risk Haematological Patients (AML under Intensive Chemotherapy): The SAPHIR Prospective Multicentre Study

2020 ◽  
Vol 6 (4) ◽  
pp. 281
Author(s):  
Jean-Pierre Gangneux ◽  
Christophe Padoin ◽  
Mauricette Michallet ◽  
Emeline Saillio ◽  
Alexandra Kumichel ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Intensive Chemotherapy ◽  
Treatment Change ◽  
Prospective Multicentre Study ◽  
Risk Period ◽  
Treatment Changes

Antifungal prophylaxis (AFP) is recommended by international guidelines for patients with acute myeloid leukaemia (AML) undergoing induction chemotherapy and allogeneic hematopoietic cell transplantation. Nonetheless, treatment of breakthrough fungal infections remains challenging. This observational, prospective, multicentre, non-comparative study of patients undergoing myelosuppressive and intensive chemotherapy for AML who are at high-risk of invasive fungal diseases (IFDs), describes AFP management and outcomes for 404 patients (65.6% newly diagnosed and 73.3% chemotherapy naïve). Ongoing chemotherapy started 1.0 ± 4.5 days before inclusion and represented induction therapy for 79% of participants. In 92.3% of patients, posaconazole was initially prescribed, and 8.2% of all patients underwent at least one treatment change after 17 ± 24 days, mainly due to medical conditions influencing AFP absorption (65%). The mean AFP period was 24 ± 32 days, 66.8% stopped their prophylaxis after the high-risk period and 31.2% switched to a non-prophylactic treatment (2/3 empirical, 1/3 pre-emptive/curative). Overall, 9/404 patients (2.2%) were diagnosed with probable or proven IFDs. During the follow-up, 94.3% showed no signs of infection. Altogether, 20 patients (5%) died, and three deaths (0.7%) were IFD-related. In conclusion, AFP was frequently prescribed and well tolerated by these AML patients, breakthrough infections incidence and IFD mortality were low and very few treatment changes were required.

scholarly journals Incidence and Risk Factors for Breakthrough Invasive Mold Infections in Acute Myeloid Leukemia Patients Receiving Remission Induction Chemotherapy

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Heena P Patel ◽  
Anthony J Perissinotti ◽  
Twisha S Patel ◽  
Dale L Bixby ◽  
Vincent D Marshall ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Multivariable Analysis ◽  
Antifungal Prophylaxis ◽  
Remission Induction ◽  
Invasive Mold Infections ◽  
Acute Myeloid

Abstract Background Despite fungal prophylaxis, invasive mold infections (IMIs) are a significant cause of morbidity and mortality in patients with acute myeloid leukemia (AML) receiving remission induction chemotherapy. The choice of antifungal prophylaxis agent remains controversial, especially in the era of novel targeted therapies. We conducted a retrospective case–control study to determine the incidence of fungal infections and to identify risk factors associated with IMI. Methods Adult patients with AML receiving anti-Aspergillus prophylaxis were included to determine the incidence of IMI per 1000 prophylaxis-days. Patients without and with IMI were matched 2:1 based on the day of IMI diagnosis, and multivariable models using logistic regression were constructed to identify risk factors for IMI. Results Of the 162 included patients, 28 patients had a possible (n = 22), probable, or proven (n = 6) diagnosis of IMI. The incidence of proven or probable IMI per 1000 prophylaxis-days was not statistically different between anti-Aspergillus azoles and micafungin (1.6 vs 5.4, P = .11). The duration of prophylaxis with each agent did not predict IMI occurrence on regression analysis. Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.004–1.081; P = .03) and relapsed/refractory AML diagnosis (OR, 4.44; 95% CI, 1.56–12.64; P = .003) were associated with IMI on multivariable analysis. Conclusions In cases that preclude use of anti-Aspergillus azoles for prophylaxis, micafungin 100 mg once daily may be considered; however, in older patients and those with relapsed/refractory disease, diligent monitoring for IMI is required, irrespective of the agent used for antifungal prophylaxis.

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