Induction Chemotherapy For Acute Leukemia Research Articles

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

The impact of antifungal prophylaxis in patients diagnosed with acute leukemias undergoing induction chemotherapy: a systematic review and meta-analysis.

Acute leukemias are complex diseases to treat and have a high mortality rate. The immunosuppression caused by chemotherapy also causes the patient to become susceptible to a variety of infections, including invasive fungal infections. Protocols established in many countries attempt to prevent these infections through the use of pharmacological antifungal prophylaxis. This systematic review and meta-analysis investigates the existing evidence for the use of antifungal prophylaxis in patients undergoing induction chemotherapy for acute leukemia, and how prophylaxis can affect treatment response and mortality. Through the use of a population-variable-outcome strategy, keywords were utilized to search online databases. The included studies were selected and the data was collected to develop descriptive results for all studies, and, for studies that met the criteria, a meta-analysis of the Relative Risk (RR) was analyzed for infection rates, in-hospital mortality, and complete remission. A total of 33 studies were included in this systematic review, with most studies presenting positive results (n = 28/33) from the use of antifungal prophylaxis. Using a random effects model, the pooled results of the meta-analysis presented lower invasive fungal infections in AML (RR: 0.527 (95% CI: 0.391; 0.709). p < 0.001). p < 0.001) and ALL (RR: 0.753 (95% CI: 0.574; 0.988). p = 0.041). when antifungal prophylaxis was used. No discernible difference was encountered in the rate of complete remission when using prophylaxis. Antifungal prophylaxis provides a lower risk of invasive fungal infections and in-hospital mortality in acute leukemia patients undergoing induction chemotherapy.

Intravascular Complications of Central Venous Catheterization by Insertion Site in Acute Leukemia during Remission Induction Chemotherapy Phase: Lower Risk with Peripherally Inserted Catheters in a Single-Center Retrospective Study.

The basilic/brachial (BBV), internal jugular (IJV), and subclavian veins (SCV) are commonly used as central venous catheter (CVC) sites. A BBV approach [peripherally inserted central catheter (PICC)] is increasingly used for short- to intermediate-term CVCs for acute leukemias undergoing cytotoxic intensive regimens. In this retrospective study, the catheterization of the BBV, IJV, and SCV in patients with previously untreated acute leukemia was assessed. The primary outcome was the composite incidence of catheter-related symptomatic deep-vein thrombosis (sDVT) and bloodstream infection (BSI) from catheterization up to 30 days later. In a 10-year period, 336 CVC were inserted in the BBV (n = 115), IJV (n = 111), and SCV (n = 110) in 336 patients suffering from AML (n = 201) and ALL (n = 135) and undergoing induction chemotherapy. The primary outcome events were 8, 20, and 27 in the BBV, SCV and IJV cohorts (2.6, 6.9, and 9.6 per 1000 catheter-days, respectively; p = 0.002). The primary outcome risk was significantly higher in the IJV-cohort than in the BBV-cohort (HR, 3.6; 95% CI, 1.6 to 7.9; p = 0.001) and in the SCV-cohort than in the BBV-cohort (HR, 2.6; 95% CI, 1.2 to 5.9; p = 0.02). PICC was a valid CVC for the induction chemotherapy of acute leukemia for the lowest risk of sDVT and BSI.

Neutropenic versus regular diet for acute leukaemia induction chemotherapy: randomised controlled trial

ObjectivesRestriction of raw fruits and vegetables (neutropenic diet) is advised for patients receiving treatment for acute leukaemia in low-income and middle-income countries (LMICs) to reduce infections despite evidence to the...

Prognostic value of Elevated Serum Inflammatory Markers in Adult Patients receiving Induction Chemotherapy for Acute Leukemia

Prognostic value of Elevated Serum Inflammatory Markers in Adult Patients receiving Induction Chemotherapy for Acute Leukemia

196 - A Phase III, Randomized Clinical Trial Comparing a Neutropenic Vs Liberalized Diets in Patients Undergoing Hematopoietic Stem Cell Transplant (HSCT) or Remission Induction Chemotherapy for Acute Leukemia/ Myelodysplastic Syndrome (MDS): Results of Interim Analysis

196 - A Phase III, Randomized Clinical Trial Comparing a Neutropenic Vs Liberalized Diets in Patients Undergoing Hematopoietic Stem Cell Transplant (HSCT) or Remission Induction Chemotherapy for Acute Leukemia/ Myelodysplastic Syndrome (MDS): Results of Interim Analysis

Randomized controlled trial of neutropenic diet versus regular diet in patients undergoing induction chemotherapy for acute leukemia

Randomized controlled trial of neutropenic diet versus regular diet in patients undergoing induction chemotherapy for acute leukemia

Single-Unit Transfusion Is Non Inferior to Double Unit Transfusion in Patients with Hematological Disorders Receiving Allogeneic or Autologous Bone Marrow Transplant or Induction Chemotherapy for Acute Leukemia: The 1versus2 Prospective Multicentric Randomized Clinical Trial

IntroductionAnemia is a common complication of hematological chemotherapy for acute leukemia and following hematopoietic stem cell transplantation (HSCT). Exposure to allogeneic blood transfusions has been associated with unfavorable outcome in several studies in a non-surgical settings. Retrospective studies in hematological intensive unit have suggested that single red blood cell (RBC) unit transfusion policy may reduce the number of RBC used in comparison with a classical double RBC unit transfusion policy, without clinical impact. The aim of the study was to demonstrate that single RBC transfusion was non inferior to the standard double RBC transfusion arm in terms of severe complication or mortality for inpatient with hematological malignancies. Key secondary endpoint, was the comparison of the numbers of RBC units transfused in each arm.MethodIn a phase 3 multicenter randomized trial, 245 adults' patients with acute leukemia requiring intensive chemotherapy or patients receiving autologous or allogeneic HSCT were randomly assigned (1:1) to receive either single RBC unit (1 RBC arm, n=125) per transfusion or double RBC (2 RBC arm, n=120) per transfusion when hemoglobin level was below 8g/dL.The primary composite endpoint was the percentage of patients who developed a grade ≥3 complications defined as stroke, transient ischemic attack, acute coronary syndrome, heart failure, elevated troponin level, intensive care unit transfer, death, new pulmonary infiltrates, and/or transfusion-related infections during hospital stays. The secondary endpoint was the number of red cell units transfused per patient per hospital stay. The primary endpoint was compared between groups by non-inferiority analysis for the proportion risk difference using Farrington-Manning method with a non-inferiority margin of 0.1, in ITT dataset.ResultsHematological disease were as followed: AML (59%), ALL (13.1%), Lymphoma (16.4%), others (11.5%). The median age was 55 years. Baseline characteristics were well balanced between the 2 arms (Figure 1A). A total of 981 and 592 transfusions have been necessary in the 1 RBC arm and 2 RBC arm, respectively. The median of RBC unit per transfusion was 1(1-1) and 2(2-2) in the 1 RBC and 2 RBC arm, respectively. The mean pre transfusion hemoglobin level was 7.49 +/- 0.83 g/dL in the 1 RBC arm and 7.46 +/- 0.67 g/dL in the 2 RBC arm (p=0.275). Hemoglobin level at discharge was 9.35 +/-1.14 g/dL in the 1 RBC arm and 9.58 +/-1.13 g/dL in the 2 RBC arm (p=0.118).The median (IQR) of red-cell units transfused per patient was 7 (4-12) in the single arm and 8 (4-12) in the double arm (p=0.65). The median number of platelet transfusion event was 7 (3.5-11.5) in the 1 RBC arm and 7 (3-13) in the 2 RBC arm (p=0.69). The median (IQR) number of red cell unit transfused per cycle and per day was 7 (3-9) and 0.28 (0.17-0.37) in the 1RBC arm and 6 (4-10) and 0.27 (0.20-0.38) in the 2 RBC arm (p=0.61 and p=0.47).The predefined non-inferiority criteria was achieved with 28 patients developing a serious complication in the 1 CGR arm (22.4%) and 28 patients in the 2 RBC arm (23.3%) (Risk difference 0.009; 95% Confidence interval [-0.0791- 0.0978] (Figure 1B).Conclusion: Single RBC transfusion policy is non inferior to double RBC transfusion policy in hematological intensive care unit for patient receiving a bone marrow transplant or intensive chemotherapy. Single RBC unit transfusion can be used safely in daily clinical practice. The single RBC transfusion policy does not reduce the number of RBC transfusion. [Display omitted] DisclosuresJardin: Genexpath: Patents & Royalties: The author is a potential inventor on a patent application for the LymphoSign, which has been licensed for by Genexpath Patents & Royalties. .

Mycafungin Prophylaxis for Adult Acute Leukemia Patients Undergoing Induction Chemotherapy

BackgroundMicafungin is a tolerable and effective prophylactic antifungal agent used during allogeneic stem cell transplantation. In this prospective single arm trial, we aimed to evaluate the potential efficacy and safety of micafungin as a prophylactic agent during first induction chemotherapy in acute leukemia patients.Materials and MethodsPatients received 50mg of micafungin intravenously once daily from initiation of induction chemotherapy to recovery of neutrophil count (absolute neutrophil count > 500/μg for consecutive days) or suspected fungal infection or occurrence of drug-related toxicity. Primary end point was the incidence of invasive fungal infection and secondary end point was overall survival and non-relapse mortality (ClinicalTrials. Gov number, NCT02440178).ResultA total of 65 patients (median age 51.0 years, male:female = 34:31) were enrolled in this study; 33 (50.8%) acute myeloid leukemia (AML), 31 (47.7%) acute lymphoblastic leukemia, and 1 acute biphenotypic leukemia, respectively. The median treatment duration of micafungin was 24 days (range 1.0-68 days). Proven invasive fungal disease occurred in 1/65 patients (1.5%) and possible fungal infection occurred in 2/65 patients (4.6%). Overall, 19/65 patients (29.2%) discontinued prophylactic micafungin and 18/65 patients (27.7%) changed micafungin to other antifungal agents; 2 patients (3.1%) for fungal infection and 15 patients (23.1%) for prolonged neutropenic fever of unknown cause. For safety, 3/65 patients (4.6%) experienced adverse events: 2 liver function abnormality (Grade 2 and 3 respectively) and 1 grade 2 allergic reaction. Induction-related mortality occurred in 3 patients, where 1 event was caused by invasive aspergillosis pneumonia. The period of from initiation of micafungin to change to other antifungal agents was 46 days (95% CI 27-64 days). There were no significant differences in adverse events and fungal infections between AML and ALL (2/33 for AML vs. 1/31 for ALL patients, p=1.000). In addition, the occurrence of fungal infection during induction therapy was associated with poor overall survival (hazard ratio 8.470, 95% confidence interval 1.048-68.465, p=0.045) in multivariable analysis. Additionally, there was no fungal infection caused by resistant organism after induction chemotherapy. Micafungin also prevented invasive fungal infection more effectively and adverse events were tolerable when compared to the results of previous prophylactic posaconazole trial (proven or probable invasive fungal infection: 2% (7/304); adverse events 19/304 (6%) in patients treated with prophylactic posaconazole) [1].ConclusionLikewise posaconazole, micafungin could be used effectively and safely as prophylactic regimen in both AML and ALL patients undergoing induction chemotherapy.Reference1. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. The New England journal of medicine. 2007;356:348-59.Figure captionFigure 1. The period of from initiation of micafungin to change to other antifungal agents [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

69-Year-Old Man With Nasal Congestion and Pre-Syncope

69-Year-Old Man With Nasal Congestion and Pre-Syncope

Detailed Assessment of Blood Culture and Clinical Factors in Febrile Neutropenia Patients with High-Risk Hematological Malignancy in Japan: A Subgroup Analysis of the Cedmic Trial

Background: During chemotherapy for hematological malignancies, febrile neutropenia (FN) is a frequent and serious complication. The causative organisms of FN vary from era to era and depending on bacterial resistance in each country. Therefore, epidemiological data are required for each era and country from prospective large clinical trials. We previously reported a prospective clinical trial indicating the importance of the D-index, a measure of neutropenia severity (CEDMIC trial, J Clin Oncol. 2020 10; 38: 815). We hypothesized that analyzing these data would provide accurate contemporary epidemiological data for hematological malignancies. Furthermore, as encountered in practice, we suspected that gram-negative (GN) bloodstream infections (BSIs) are more common at high body temperatures (BTs) than at low BTs and examined the relationship between causative bacteria and BT. Patients and Methods: Between June 2013 and April 2017, we enrolled patients with hematological malignancies aged 16-79 years post-chemotherapy or -stem cell transplantation (SCT) with expected neutropenia durations &amp;gt;7 days. Neutrophil counts &amp;lt;500/mL reflected neutropenia, and all fevers had axillary temperatures ≥37.5°C. Prophylactic antibiotics (Abx) were drugs administered post-chemotherapy and pre-FN onset. The FN incidence and blood culture (BC) positivity rate were examined in 4 treatment groups: allogeneic SCT (Allo-SCT), autologous SCT (Auto-SCT), induction chemotherapy for acute leukemia, and other treatments. Results: In total, 423 patients were enrolled, and 413 (median age: 56 years) were included in the intention-to-treat analyses (Table 1). The treatments included induction chemotherapy (n=67), Allo-SCT (n=106), Auto-SCT (n=158), and others (n=82). Prophylactic Abx were administered in 281 (68.5%) patients (only quinolone, n=222; with β-lactam, n=59). Prophylaxis rates were significantly higher in the Allo-SCT (n=94, 88.7%, p&amp;lt;0.001) and induction chemotherapy (n=49, 73.1%, p&amp;lt;0.017) groups. FN occurred in 356/413 patients (86.4%, Table 1). The Allo-SCT group had a higher FN incidence than that in the other treatments group (93.4% vs. 72%, p&amp;lt;0.001). D-indices ≥5500 and &amp;lt;5500 were associated with FN incidences of 100% and 81.8%, respectively (p&amp;lt;0.001). Prophylaxis did not reduce the FN incidence. In total, 1272 BC sets were collected from 356 patients with FN. At FN onset, BCs were collected from 346 patients; 72 (20.8%) were positive (Table 2). Among initial BCs, 46 (63.9%) harbored gram-positive (GP) and 28 (38.9%) harbored GN bacteria. Three patients had multiple bacterial infections. The 2 most frequent GP bacteria were coagulase-negative Staphylococcus (n=21, 44.7%) and viridans streptococci (n=14, 29.8%). The 3 most frequent GN bacteria were Escherichia coli (n=13, 44.9%), Klebsiella pneumoniae (n=4, 13.8%), and Pseudomonas aeruginosa (n=4, 13.8%). Among initial BCs, prophylactic Abx use did not reduce BC positivity. However, the GN BSI incidence was significantly lower in the prevention group vs. non-prevention group (23.8% vs. 56.7%, p=0.007). Among patients who received prophylactic β-lactam, GN BSIs did not occur. Maximum BTs (maxBTs) were significantly higher in patients with positive BCs than negative BCs (38.4°C vs. 38.0°C, p&amp;lt;0.001). The BTs associated with GN BSIs were significantly higher than those associated with negative BCs and GP BSIs (38.7°C vs. 38.0°C vs. 38.2°C, p&amp;lt;0.001, Figure 1). The maxBTs and BC positivity rates were strongly related (Table 3). The BC positivity rates were significantly higher in patients with BTs ≥38°C vs. &amp;lt;38°C (26.5% vs. 14.5%, p=0.008), 38.5°C vs. &amp;gt;38.5°C/&amp;lt;38.5°C (39.7% vs. 15.3%, p&amp;lt;0.001), and ≥39°C vs. &amp;lt;39°C (52.6% vs. 16.9%, p&amp;lt;0.001). Among patients who did not receive prophylactic Abx (n=106), the GN BSI positivity rate was significantly lower in patients with maxBTs &amp;lt;38°C vs. ≥38°C (14.3% vs. 76.2%, p=0.007). Conclusion: In FN patients with high-risk hematological malignancies in Japan, the frequency of GP BSIs is high. Prophylactic Abx use reduces the GN BSI risk but not the FN or BSI risk. Fever severity and BC positivity at FN onset are strongly associated. The BTs of patients with GN BSIs are high. Disclosures Kanda: Astellas Pharma: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Meiji Seika Kaisha: Honoraria; Merck Sharp &amp; Dohme: Honoraria; Pfizer: Honoraria, Research Funding; Shionogi: Research Funding; Celgene: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Eisai: Honoraria, Research Funding; Novartis: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Honoraria; Shire: Honoraria; Daiichi Sankyo: Honoraria; Ono Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria, Research Funding; Mochida Pharmaceutical: Honoraria; Otsuka: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Janssen: Honoraria; Mundipharma: Honoraria. Kimura:Takeda Pharmaceuticals: Honoraria; Astellas Pharma: Honoraria; Pfizer: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Merck Sharp &amp; Dohme: Honoraria; Nippon Kayaku: Honoraria; Kyowa Hakko Kirin: Honoraria; Ono Pharmaceutical: Honoraria; Celgene: Honoraria; Asahi Kasei: Honoraria. Oyake:Astellas Pharma: Honoraria; Bayer: Research Funding; Chugai Pharma: Honoraria, Research Funding; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Honoraria; Bristol-Myers Squibb Japan: Honoraria; Pfizer: Honoraria; Sionogi: Research Funding. Tamura:Asahi Kasei: Honoraria; Ono Pharmaceutical: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria.

S3388 Tormenting Typhlon: A Rare Case

INTRODUCTION: Neutropenic enterocolitis is acute inflammation of cecum, ascending colon, terminal ileum and appendix, seen in immunocompromised patients with leukemia. Incidence in healthy adults unknown, few cases due to clostridium perfringens type A. More seen in neutropenic children/adults who had undergone induction chemotherapy for acute leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes, aplastic anemia, acquired immunodeficiency syndrome, cyclic or drug induced neutropenia or immunosuppressive therapy. Frequency is increasing with use of cytotoxic agents. CASE DESCRIPTION/METHODS: 48 year old male with no history presented with 8 days of worsening abdominal pain, few days of watery brown diarrhea, no neutropenia. CT showed acute appendicitis, perforation, periappendiceal collection and marked inflammatory reaction. Patient was taken for laparoscopic appendectomy. There was generalized peritonitis, pus with feculent odor. Appendix was inflamed, not perforated. Cecum had areas with false membrane consistent with cecal gangrene. Abscess posterior to cecum was fusing medially towards mesentery of small bowel and ascending colon. Right hemicolectomy with ileal transverse anastomosis was done. Pathology consistent with gangrenous typhlitis with retroperitoneal abscess. Intraop cultures were positive for ecoli. Patient was treated with IV antibiotics and then oral. DISCUSSION: Typhlitis, is neutropenic enterocolitis of ileocecal region. Cecum is affected due to diminished vascularization. Signs & symptoms: right lower quadrant pain, fever, abdominal distention, cramping, tenderness, nausea, vomiting, diarrhea, and hematochezia. Histology: bowel wall thickening, ulcers, mucosal loss, intramural edema, hemorrhage and necrosis. Patients suspected of typhlitis should have oral & IV contrast for CT. Blood & stool cultures, and C dificile toxin testing. CT can show bowel wall thickening, bowel dilation, mesenteric stranding, mucosal enhancement and pneumatosis. Cultures positive for polymicrobial infection. Treatment in patients without complications: bowel rest, NG suction, IV fluids, nutritional support & broad spectrum antibiotics covering pseudomonas, e coli, gram-negative bacilli & anaerobes. Surgical intervention if signs of perforation, bleeding despite correction of coagulopathy and cytopenias. It mimics appendicitis like in our patient leading to immediate surgery. It is important to consider neutropenic enterocolitis in the differential diagnosis of patients that are not immunocompromised.Figure 1Figure 2

Efficacy and safety of micafungin in empiric and D-index-guided early antifungal therapy for febrile neutropenia; A subgroup analysis of the CEDMIC trial

ObjectivesThe D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. MethodsFrom the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. ResultsThe proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2–79.4) and 79.6% (71.0–86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2–80.9%) and 78.0% (65.3–87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. ConclusionsThe efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT.

273. Low Positive Predictive Value of β-d-Glucan in Hematology Patients Receiving Antimold Prophylaxis

BackgroundDetection of β-D-glucan (BDG) in serum is recognized as the mycological evidence in the diagnosis of invasive fungal infection (IFI). However, its diagnostic value in low prevalence of IFI has not been elucidated. We aimed to examine the performance of BDG in hematology patients receiving antimold prophylaxis.MethodsWe retrospectively reviewed all BDG results performed for the purpose of diagnosis or surveillance for IFI in hematology patients receiving posaconazole or micafungin prophylaxis from January 2017 to February 2019 in a tertiary hospital. At least two consecutive positive results of BDG were regarded as positive BDG. All the episodes were classified into true-positive (TP, positive BDG with probable/proven IFI), true-negative (TN, negative BDG without probable/proven IFI), false-positive (FP, positive BDG without probable/proven IFI), false-negative (FN, negative BDG with probable/proven IFI), and nonevaluable (could not be determined for the occurrence of breakthrough IFI). When BDG test was performed in the setting of persistent fever ≥72 hours in spite of broad-spectrum antibiotics or with a suspicion of IFI, it was defined as a diagnostic BDG episode, while others were defined as a surveillance BDG episode.ResultsOf a total of 140 episodes, 24 episodes were non-evaluable. Among 116 evaluable episodes, 75 received induction chemotherapy for acute leukemia or myelodysplastic syndrome, 35 underwent stem cell transplantation, and 10 had intensive treatment for graft-vs.-host disease. There were three episodes of probable/proven IFI (2.6%). Ninety-one (78.4%) were performed with diagnostic purpose, while 25 (21.6%) were performed for surveillance. TP, TN, FP, and FN were 2 (1.7%), 91, 22, and 1, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 66.7%, 80.5%, 8.3% and 98.9%, respectively. PPV was 13.3% and 0% in diagnostic and surveillance BDG episodes, respectively.ConclusionThe PPV of BDG was low in hematology patients receiving antimold prophylaxis, even in the diagnostic-driven episodes. The routine screening of BDG is not helpful, and the BDG test may be used for exclusion of IFI rather than for diagnosis in these patients. Disclosures All authors: No reported disclosures.

Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia

Acute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo “repeat therapy” (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. To test this hypothesis, we analyzed the bacterial microbiome profiles of thrice-weekly stool samples from 20 intensively treated AL patients (first induction: 13, repeat therapy: 7) by 16S rRNA sequencing. In mixed-effects modeling, repeat therapy was a significant predictor of Enterococcus expansion (P = 0.006), independently of antibiotic exposure, disease type, feeding mode, and week of chemotherapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.

Management of Venous Thromboembolism (VTE) in Thrombocytopenic Patients Undergoing Induction Chemotherapy for Acute Leukemia

Introduction: Management of VTE in patients with hematological malignancies is challenging as these patients often have thrombocytopenia and are at increased risk for bleeding. The International Society of Thrombosis and Hemostasis (ISTH) guidance statement recommends adjusting anticoagulation based on the severity and acuity of VTE and considering platelet transfusion support to maintain platelet counts above >50K/µL to facilitate full-dose anticoagulation (AC) in patients with acute VTE with high-risk features. For acute VTE with low-risk features, a dose-modified strategy such as half- or prophylactic-dose AC, depending on platelet count, is recommended. While the risk of AC with supportive platelet transfusions may be justified in patients with severe VTE, lower-dose AC without platelet transfusion support may be adequate for patients with non-severe VTE and may reduce the risk for development of platelet alloantibodies. To better understand practice patterns at our institution, we reviewed the management of VTE in patients with acute leukemia over an 8-year period.Methods: We retrospectively reviewed all patients with acute leukemia who developed acute VTE during induction chemotherapy at Dartmouth-Hitchcock Medical Center for the 8-year period (2006-2013). Primary outcomes were 1) objectively confirmed, recurrent symptomatic VTE, and 2) clinically significant bleeding within 1 month after diagnosis of the index VTE. Secondary outcomes included IVC filter use and platelet alloantibody development within 3 months after diagnosis of VTE. We classified VTE events as acute or subacute/chronic and severe or non-severe. An acute event was defined as a new VTE diagnosed during the index hospitalization, while a subacute/chronic event was defined as a VTE that occurred prior to the index hospitalization for which the patient was being treated with AC during the hospitalization. A severe VTE was defined as a DVT involving femoral or more proximal vein segments, the SVC, cerebral veins or any PE. Non-severe events included UE DVT and distal DVT. We classified treatment at the time of diagnosis of VTE into one of the following categories: 1) full-dose AC with platelet transfusion to maintain platelet count >25-50K/µL, 2) half-dose AC with platelet transfusion to maintain platelet count >25-50K/µL, 3) prophylactic-dose AC without additional platelet transfusion beyond the standard of care, 4) no anticoagulation. We recorded the number of IVC filters inserted in each category. Descriptive statistics, including mean and standard deviation for continuous variables, and percentage and frequency for categorical variables, were calculated.Results: 40 subjects met entry criteria (55% male) with median age of 57.5 years. The majority (88%) had acute myeloid leukemia. Acute VTE was identified in 80% and VTE was severe in 55%. The degree of thrombocytopenia at the time of VTE diagnosis was <10K/µL (2.5%), 10-25K/µL (25%), 25-50K/µL (40%), and >50K/µL (32.5%). Subjects were initially treated with full-dose AC (60%), half-dose AC (5%), prophylactic-dose AC (12%) or no AC (22.5%). An IVC filter was inserted in 10 subjects (25%), and five subjects (12%) developed platelet alloantibodies. Seventeen subjects (42%) experienced bleeding complications within the first month of VTE diagnosis, six of which (35%) were clinically significant. Half of these were on full-dose AC, and half underwent insertion of an IVC filter. Two subjects (5%) had VTE recurrence within 1 month, and in both cases, AC had been discontinued prior to the recurrence due to bleeding complications.Conclusion: We found that management of VTE in patients with acute leukemia and thrombocytopenia varies and that the risk for bleeding complications was high irrespective of AC dose. We also uncovered the problem of VTE recurrence due to premature discontinuation of AC as a result of bleeding and observed a surprisingly high incidence of platelet alloimmunization. Dose-modified AC without platelet transfusion support may be an attractive alternative for treatment of VTE in this population, but further study is required to balance bleeding and thrombosis risk. DisclosuresNo relevant conflicts of interest to declare.

Co-administration of proton pump inhibitors and/or of steroids may be a risk factor for low trough concentrations of posaconazole delayed-released tablets in adult patients with haematological malignancies.

The aim of this study was to determine clinical variables associated with posaconazole exposure among adult patients with haematological malignancies who received posaconazole tablets for prophylaxis of invasive fungal infections (IFIs). The study population included adult patients with haematological malignancies who received posaconazole delayed-release tablets for prophylaxis of IFIs after induction chemotherapy for acute leukaemia or graft-versus-host-disease (GVHD) complicating hematopoietic stem cell transplantation (HSCT) in the period January 2016-December 2017. Sixty-six consecutive patients with 176 posaconazole Cmin were included for evaluation in the study. Subtherapeutic posaconazole concentrations (< 0.7mgl-1 ) were observed at least once in 33.3% of patients (22/66), and overall in 17.0% of therapeutic drug monitoring (TDM) episodes (30/176). At multilevel linear regression, use of PPIs (P=0.008), use of intermediate or high dose steroids (>0.7mgkg-1 daily) (P=0.022) and male gender (P=0.025) were significantly associated with decreased Cmin , whereas time from starting therapy (P=0.032) was associated with increased Cmin in our patient population. Posaconazole exposure during treatment with delayed-released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.

Outcomes in obese patients undergoing induction therapy for acute leukemia.

Obesity continues to be a growing epidemic in the United States. Guidelines published by American Society of Clinical Oncology in 2012 recommend dosing chemotherapy using actual body weight. However, the guidelines do not provide guidance for patients with hematologic malignancies. The objective of this study was to evaluate outcomes in obese patients undergoing induction chemotherapy for acute leukemia versus nonobese patients using actual body weight dosing. This single center retrospective chart review from November 2012 to August 2016 evaluated newly diagnosed leukemia patients who received induction chemotherapy dosed on actual body weight. The primary outcome was rate of complete remission following induction chemotherapy between obese patients versus nonobese patients. Secondary outcomes included time to absolute neutrophil count and platelet recovery, incidence of febrile neutropenia, clinical or microbiological infections, early (0-15 days) and in-hospital mortality, and overall survival at six months. Obese patients had similar rates of complete remission versus nonobese patients with acute myeloid leukemia (60% vs. 61.9%; p = 0.86) and acute lymphoblastic leukemia (87.5% vs. 92.8%; p = 0.31). Obese patients with acute myeloid leukemia were more likely to receive re-induction chemotherapy following 14-day bone marrow biopsy vs. nonobese patients (53.3% vs. 23.2%; p = 0.019). There were no significant differences in secondary outcomes in either group when comparing obese versus nonobese patients. Obese patients have similar rates of complete remission compared to nonobese patients following induction chemotherapy in acute leukemia. Continued research is needed to determine optimal dosing and long-term outcomes in this patient population.

Adherence to, and outcomes of, a galactomannan screening protocol in high-risk hematology patients.

A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf). Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%, p = 0.02; 46% vs. 26%, p = 0.014; and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

Uric acid as a novel biomarker for bone-marrow function and incipient hematopoietic reconstitution after aplasia in patients with hematologic malignancies.

Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total). During therapy, UA levels declined from normal values to hypouricemic values (all p < 0.001). Alongside hematopoietic recovery, UA serum levels returned to baseline values. During aplasia, UA levels remained low and started steadily increasing (defined as >two consecutive days, median one 2-day increase) at a median of 1 day before rising leukocytes in allogeneic HCT (p = 0.01) and together with leukocytes in autologous HCT (median one 2-day increase). During induction chemotherapy, a UA increase was also observed alongside rising leukocytes/neutrophils but also several times during aplasia (median 3 increases). Most HCT patients had no detectable leukocytes during aplasia, while some leukocytes remained detectable after induction therapy. No increase in UA levels was observed without concomitant or subsequent rise of leukocytes. Changes in UA serum levels can indicate incipient or remaining immunological activity after HCT or induction therapy. They may, therefore, help to differentiate between PGF and GF.