Acute Leukemia Undergoing Induction Chemotherapy Research Articles

Dental and Periodontal Treatment Need after Dental Clearance Is Not Associated with the Outcome of Induction Therapy in Patients with Acute Leukemia: Results of a Retrospective Pilot Study.

This retrospective pilot study aimed to detect whether remaining dental/periodontal treatment need and periodontal inflammation after dental clearance would be associated with the initial therapy outcome of adult patients with acute leukemia undergoing induction chemotherapy. Different parameters were assessed from the patients' records: initial blood parameters, blood parameters during initial chemotherapy, leukemia/therapy related complaints, duration of fever, microbiological findings (blood and urine), as well as patients' survival. Dental treatment need was defined as the presence of at least one carious tooth; periodontal treatment need was determined by the presence of probing depth ≥3.5 mm in at least two sextants. To reflect periodontal inflammation, the periodontal inflamed surface area (PISA) was applied. Thirty-nine patients were included. A dental treatment need of 75% and periodontal treatment need of 76% as well as an average PISA of 153.18 ± 158.09 were found. Only two associations were detected: periodontal treatment need was associated with thrombocyte count after 7 days (p=0.03), and PISA was associated with erythrocyte count three days after induction of therapy (p=0.01). It can be concluded that remaining dental and periodontal treatment need as well as periodontal inflammation after dental clearance is not associated with the outcome of induction therapy in adult patients with acute leukemia.

Radiation-Free Protocol for Patients with Acute Lymphoblastic Leukemia and Mixed Phenotype Acute Leukemia Undergoing Induction Chemotherapy and Allogeneic Hematopoietic Cell Transplantation - a Multicenter Historical Prospective Study

Introduction: Acute lymphoblastic leukemia (ALL) and mixed phenotype acute leukemia (MPAL) in adults are associated with a cure rate of only 20 and with a tendency for relapse to the CNS. Total body irradiation (TBI)-based high dose therapy and allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for these patients, however, the median age for ALL in adults is 65 years and thus, majority of patients are not suitable candidates for high dose conditioning and HCT. Therefore, novel approaches are needed. Thiotepa is an alkylating lipophilic agent that result in achieving up to 100% cerebrospinal fluid levels and has been used in ablative regimens (total dose of 20 mg/kg), Christopoulos BBMT 2012. Methods: We aimed to test this regimen in patients with ALL/MPAL who were not eligible for a standard TBI-containing regimen and capped the thiotepa dose at 14 mg/kg (for patients given myeloablative regimen divided to 2 doses on Day -5 and -4) or at a dose of 10-12 mg/kg (in patients given a reduced intensity regimen). In addition patients were given BCNU at a dose of 400 mg/m^2 on Day -6 and fludarabine at a dose of 25 mg/m^2 on Day -6 to -4. We omitted entirely cranial irradiation, however Intrathecal (IT) therapy was allowed pretransplant (only) as per physician discretion. GVHD prophylaxis consisted of cycslosporine-methotrexate and ATG in cases of non-sibling donors. Results: Between July 2014 and June 2019, 22 patients from 3 centers in Israel were eligible for the protocol. Median follow up was 17 (range, 3-61) months. Median age at transplant was 51 (range, 22-68), Table. Majority of the patients (59%) had a CR1 with MRD negative disease . Ten patients (45%) were given a myeloablative regimen (>14 mg/kg of thiotepa) and 12 patients (55%) were given a reduced intensity regimen (10-12 mg/kg of thiotepa), majority (7 patients, 32%) because of age>60 years. Eight patients (36%) had a sibling donor, 12 patients (55%) had an unrelated donor and 2 (9%) had a 1 antigen-mismatch unrelated donor. GVHD prophylaxis consisted for all patients cyclosporine and a short course of methotrexate.Three patients (14%) developed sinusoidal obstruction syndrome (1 patient, severe). 7 patients (32%) had microbiology documented infections and 16 patients (73%) had grade 3-4 mucositis. All patients who survived (n=18, 82%) had a day 30-whole marrow donor chimerism > 96%. Cumulative incidences of grade 2-4 and grade 3-4 acute GVHD at day 200 were 51%(95% CI 35%-62%) and 11%(95% CI 5%-24%), respectively. Cumulative incidence of 2 year-moderate-severe chronic GVHD was 52% (95% CI 41%-74%). Relapse occurred in only 3 patients and all occurred within 4 months from HCT with a 2 year cumulative incidence of 17%(95% CI 12%-21%). Cumulative incidences of non-relapse mortality at 30 days, 3 months and 2 years after HCT were 15%(95% CI 8%-17%), 24%(95% CI 12%-32%) and 24%(95% CI 12%-32%), respectively. At time of data extraction 14 patients were alive. Cumulative Incidences of 2-year overall survival for CR1 patients with MRD negative disease and for non-CR1 patients with MRD negative disease at HCT were 70%(95% CI 61%-87%) and 62%(95% CI 50%-73%), respectively (p=.59), Figure. Factors associated in cox regression model with decreased overall survival were CNS involvement at diagnosis (p=.06, HR=2.24) and older age (p=.045, HR=1.5), while disease status at HCT, having a sibling donor, and intensity of conditioning were not predictive. Conclusions: This study shows that a thiotepa based regimen has substantial activity in patients with ALL, even in those who are older than 60 years and in patients intelligible to TBI. Reduced doses of thiotepa may have comparable efficacy and a lower toxicity profile when compared to higher doses and should be further investigated in this cohort of patients. Disclosures No relevant conflicts of interest to declare.

Micafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy

BackgroundMicafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML).MethodsMedically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity (Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy.ResultsThe 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1–68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety.ConclusionsOur study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML.Trial registrationClinicaltrials.gov NCT02440178, registered May 12th 2015.

Psychosocial Experiences of Young Adults Diagnosed With Acute Leukemia During Hospitalization for Induction Chemotherapy Treatment.

The diagnosis of cancer for anyone is a time of fear and uncertainty. For young adults (YAs) diagnosed with acute leukemia (AL), there are the additional challenges related to lengthy aggressive in-hospital treatment, multiple concurrent symptoms, and decreased well-being. The purpose of this study was to explore the experiences of YAs with AL undergoing induction chemotherapy. This study used a nested qualitative longitudinal design with a convenience sample. Qualitative data were collected using semistructured interviews, and participants were invited to maintain journals. The semistructured interviews were audiotaped, transcribed, and loaded into Atlas.ti for analysis. Common themes and categories were verified and used to disseminate the findings. Seven YAs, mean age 32 (SD, 4) years, participated in this study. Three thematic classifications emerged: getting through, supported yet isolated, and information exchange preferences, which detail how these YAs processed and coped during treatment. The findings from this study provide important insights for nurses regarding coping mechanisms that YAs apply, which included relying on technology and social media platforms. Additionally, the YAs in this study discussed their need for information. The findings from this study may provide insights for clinicians currently caring for YAs with AL, while also directing future palliative care research endeavors.

Endurance and resistance training in patients with acute leukemia undergoing induction chemotherapy-a randomized pilot study.

Acute leukemia (AL) and its initial treatment can impair physical functioning and capacity significantly. Exercise as a countermeasure has been investigated in few studies confirming its feasibility and safety during intensive induction chemotherapy, but the relative effects of diverse exercise programs have not been analyzed. Therefore, we aimed to investigate independent effects of endurance and resistance training on physical capacity and quality of life (QOL). Twenty-nine adult AL patients were randomly allocated to an endurance (EG), resistance (RG), or control (CG) group. The intervention took place during induction chemotherapy with three exercise sessions per week for 30-45min each. Endurance capacity at individual anaerobic threshold, maximum knee extension and flexion strength, standardized phase angle (SPA), and QOL were measured at baseline prior to induction chemotherapy and before discharge. Endurance capacity changed in neither the EG, RG, or CG (P = 0.104); descriptively, the EG (- 0.05W/kg) and RG (- 0.04W/kg) exhibited a smaller decrease than CG (- 0.22W/kg). We noted a significant difference in knee extension strength (P = 0.002); RG improved their maximum strength (+ 0.14Nm/kg), while the EG's (- 0.13Nm/kg) and CG's (- 0.19Nm/kg) was significantly reduced. QOL and SPA revealed no change after the intervention. We conclude that resistance training is a key component when exercising during induction chemotherapy: it improved maximum strength, but also influenced endurance capacity even during intensive treatment. Considering the prognostic value of physical function, we strongly propose integrating exercise, especially resistance-based training, already during induction chemotherapy to preserve AL patients' physical capacity and functional status.

1027P - Surveillance stool culture and its association with febrile neutropenia in patients with acute leukemia (AL) undergoing induction chemotherapy

Background: Febrile neutropenia remains one of the major concerns of intensive chemotherapy and contributes significantly to morbidity, health care expenditure and mortality. Colonization of gut by MDR bacteria is regarded as a potential risk factor for subsequent infection with the same organism during febrile neutropenia. In this study, we aim to find the profile of surveillance stool culture and its association with febrile neutropenia in patients of acute leukemia undergoing induction chemotherapy. Methods: Newly diagnosed patients of acute leukemia eligible for intensive chemotherapy were recruited for the study. Baseline stool microscopy and culture sensitivity was done to identify colonization with pathogenic bacteria. Blood and other samples were collected during febrile neutropenia. Association between surveillance stool culture and subsequent infections were studied. Results: A total of 106 patients were recruited from November 2015 to March 2017. 59 patients were pediatric AL with median age of 10 years and 47 patients were adult AL with median age of 33 years. 68.86% of patients had gut colonization with bacteria of which 33.01% were MDR while 35.84% were non-MDR. Most common MDR bacteria colonizing gut were E. Coli (62.16%) and Klebsiella Pneumonia (21.82%). A total of 264 blood cultures were taken from 68 patients who developed 114 episodes FN during induction. Blood culture positivity rate was 17.80% with 68.08% of the isolates being MDR. Most common MDR isolates were Klebsiella (28.12%) and pseudomonas (18.75%). 34.28% of patients colonized with MDR bacteria developed MDR sepsis during induction compared to 23.68% non MDR colonizers. Induction mortality was 20% in MDR colonizers compared to 10.52% in non-colonizers. Conclusions: Our study suggests that a significant proportion of patients are colonized with MDR bacteria and there is a high prevalance of MDR sepsis during induction. MDR sepsis and induction mortality were higher in patients colonized with MDR bacteria compared to non MDR bacteria. Legal entity responsible for the study: JIPMER Funding: JIPMER Disclosure: All authors have declared no conflicts of interest.

Micafungin Versus Posaconazole Anti-Fungal Prophylaxis in Adult Patients with Acute Leukemia Undergoing Induction Chemotherapy

AbstractAbstract 3556 Introduction:Posaconazole has been shown to be effective in reducing the incidence of invasive fungal infections (IFI) in high-risk, neutropenic leukemia patients following induction chemotherapy. Its clinical utilization, however, may be limited by decreased oral absorption secondary to mucositis and other adverse events that occur during therapy. Micafungin is a broad spectrum antifungal agent approved for prophylaxis in stem cell transplant recipients. Nonetheless, its safety and efficacy in neutropenic leukemia patients has not been established. We therefore designed a prospective randomized study comparing micafungin to posaconazole as anti-fungal prophylaxis in patients with acute leukemia undergoing induction chemotherapy. The aim of this interim analysis is to compare (1) the total time on study drug between the micafungin and posaconazole treatment groups and (2) the percentage of patients completing the planned treatment course between the two groups. Methods:Patients > 18 years of age were eligible for study with newly diagnosed acute leukemia (either AML or ALL) or MDS who were to receive myeloablative therapy with an anticipated neutropenic period of at least 7 days following anthracycline-based chemotherapy. Patients with first relapse of AML and ALL were also eligible. Patients who were pregnant, unable to swallow, hypersensitive to azoles, taking medications known to interact with posaconazole, and those receiving dasatinib were excluded from the study. Patients with a history of invasive fungal infection requiring therapy within 30 days of randomization, prolonged QTc interval on EKG, and moderate or severe liver dysfunction were also excluded.Participants were randomized to receive micafungin (100 mg IV daily) or posaconazole (400 mg orally twice daily). The absolute neutrophil count (ANC) was monitored daily. Neutrophil recovery was defined as ANC ≥500 cells/μl for two consecutive days. Prophylaxis completion was defined as continuation of treatment until neutrophil recovery or 28 days after treatment initiation, whichever was earlier. Prophylaxis failure was defined as discontinuation of study drug due to adverse event, persistent neutropenic fever requiring change to an alternative antifungal agent, or withdrawal from the study before 28 days. Fungal markers (Galactomannan, BD glucans) were followed weekly from randomization to neutrophil recovery. Continuous and categorical variables were tested with Wilcoxon rank-sum test and chi-square tests, respectively. Kaplan-Mayer method was used to measure the completion rates of anti-fungal prophylaxis, and the log-rank test was used to compare the completion between two groups. Results:From March 2011 to May 2012, 46 patients were randomized to prophylaxis with either micafungin (n=23) or posaconazole (n=23). The two groups did not differ in age, sex, race, neutropenic duration, or liver dysfunction (p=0.35, 0.56, 0.36, 0.07 and 0.4366, respectively). Nineteen patients (83%) completed micafungin therapy while only eight (35%) completed posaconazole (p=0.001). Median number of days on prophylaxis was 18.2 days for the micafungin group and 14.8 days for the posaconazole group (p=0.0584). Eight patients (34.8%) were removed from study in the posaconazole group after developing colitis or being made NPO by the treating physician. There were no positive fungal markers during the study period. Nine patients (20%) underwent bronchoscopy because of new chest CT abnormalities while on study drug. Bronchoalveolar lavage was sent for routine cultures, cytology, Galactomannan, and pan-fungal PCR (University of Washington). Two patients (one from each treatment group) had IFI identified by PCR (Rhodotorula nothofagi and Cryptococcus species). Conclusions:For patients undergoing myeloablative therapy for the treatment of acute leukemia or MDS, micafungin prophylaxis is associated with a superior completion rate and longer time to failure of prophylaxis compared to posaconazole. In addition, there is no difference in breakthrough fungal infections between the two treatment groups. Micafungin as antifungal prophylaxis is well tolerated and appears as effective as posaconazole prophylaxis for leukemia patients with prolonged neutropenia from induction chemotherapy. Our ongoing clinical study will continue to assess the efficacy of micafungin in this patient population. Disclosures:No relevant conflicts of interest to declare.

Fluoroquinolone Prophylaxis Following Induction Chemotherapy in Patients with Acute Leukemia: Patterns of Infection

AbstractAbstract 2077Neutropenic fever is an important cause of morbidity and mortality in patients (pts) with acute leukemia who receive cytotoxic chemotherapy. Fluoroquinolone prophylaxis has been shown in randomized controlled trials to decrease the rate of neutropenic fever, with a trend towards decreased mortality in meta-analyses. The merit of fluoroquinolone prophylaxis has been debated based on the concerns of emerging antibiotic resistance, lack of a clear survival benefit and fluoroquinolone therapy related complications such as C. difficile colitis. This retrospective single-institution review examined the pattern of infections with the use of antimicrobial prophylaxis in pts with acute leukemia undergoing induction chemotherapy. Methods:Pts >/=18y who completed induction chemotherapy for AML or ALL between Jan 2006 and Dec 2010 were eligible for the study if they received or could have received antibiotic prophylaxis for at least 1 day post-induction. Pts were excluded if they presented with fever or developed fever during induction and were continued on systemic antibiotics. Pts were stratified based on receipt of antibiotic prophylaxis versus no prophylaxis. The primary study endpoint was neutropenic fever episodes, with secondary endpoints of documented bacteremia, fungemia, C. difficile colitis, as well as time to onset of fever, length of hospital stay and mortality. Fever was defined as single oral temperature of 38.3 C or greater, or a temperature of 38.0 C for a period of an hour or longer, and neutropenia was defined as an ANC <500 cells/mm3 or an ANC that was expected to decrease to <500 cells/mm3 over the subsequent 48 hours. Odds ratios with 95% confidence intervals were calculated for neutropenic fever episodes, bacteremia, fungemia, C. difficile colitis and mortality. Time to onset of fever and length of stay were analyzed using the Wilcoxon rank-sum test. Results:Eighty-three consecutive pts with AML or ALL meeting the eligibility criteria were included in the study. Thirty-six pts received antibiotic prophylaxis while 47 did not. A significant decrease was noted in the rates of neutropenic fever and time to onset of fever for pts receiving prophylaxis (Table). There was no difference between prophylaxis versus no prophylaxis for other study endpoints.Patients receiving prophylaxis1Patients not receiving prophylaxisOdds Ratio for Prophylaxis (95% confidence interval), (p-value)Number of pts3647Neutropenic Fever27 (75%)44 (94%)0.21 (0.03–0.93), (0.03)Severe sepsis0 (0%)2 (4%)0 (0.00–6.95), (NS)Septic shock1 (3%)2 (4%)0.65 (0.01–12.88), (NS)Bacteremia3 (8%)11 (23%)0.30 (0.08–1.16), (NS)Fungemia2 (6%)1 (2%)2.71 (0.24-31.08), (NS)C. difficile infection4 (11%)5 (11%)1.05 (0.19–5.32), (NS)Mortality1 (3%)2 (4%)0.65 (0.01-12.88), (NS)Time to onset of fever (days)12.211.3p = 0.09Length of Stay (days)13.415.0p = 0.306133 of 36 pts received moxifloxacin prophylaxis, one patient each received amoxicillin, amoxicillin/clavulanate, and ciprofloxacin. Conclusions:This retrospective review found a significantly lower rate and delay in onset of neutropenic fever in AML and ALL patients receiving fluoroquinolone prophylaxis, but no difference in patterns of infection compared with non-prophylaxed pts. A trend towards fewer episodes of bacteremia in the prophylaxis group was noted, but did not reach statistical significance. Further data collection and analysis is ongoing for pts undergoing consolidation chemotherapy for AML and ALL or re-induction chemotherapy following relapse for assessment of neutropenic fever episodes and patterns of infection. Disclosures:No relevant conflicts of interest to declare.

The use of anti‐D to improve post‐transfusion platelet response: a randomized trial

Patients undergoing induction chemotherapy for acute leukaemia often become refractory to platelet transfusions. Increased clearance of transfused platelets due to alloimmune destruction has been identified as one of the primary mechanisms contributing to this refractory state. We performed a double-blind randomized trial to determine whether the administration of anti-D to Rh-positive individuals could prevent the refractory state and improve post-transfusion platelet response. Rh-positive patients with acute leukaemia undergoing induction chemotherapy and requiring platelet transfusions were allocated to weekly intravenous anti-D (20 micrograms/kg) or placebo. Platelets and red cell concentrates were administered according to standardized transfusion guidelines. Outcome measures included platelet transfusion utilization, red cell utilization, platelet recovery 18-24 h post-infusion, and the percentage of patients refractory to platelet transfusion. There were 43 patients studied: 21 received anti-D and 22 saline placebo. The mean number of platelet concentrates required per day of observation was 0.59 (SD 0.22) in the anti-D group and 0.61 (SD 0.22) in the placebo group, P = 0.86. No difference was detected between groups in terms of platelet recovery post-infusion, refractoriness to platelet transfusion or frequency of infection (P = 0.97). Red cell concentrate utilization was significantly increased in the anti-D group compared to the placebo group, 0.58 units per day versus 0.37 units per day respectively, P = 0.005. We conclude that the use of anti-D did not improve post-transfusion platelet response in Rh positive patients with acute leukaemia, but did result in an increased need for red cell transfusion.