Increased body mass index is a risk factor for acute promyelocytic leukemia.

Introduction: Obesity has become increasingly prevalent worldwide and is a risk factor for many malignancies. We studied the correlation between body mass index (BMI) and the incidence of acute promyelocytic leukemia (APL), non-APL acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and control hospitalized patients without leukemia in the same community. Methods: Multi-center, retrospective analysis of 71,196 patients: APL (n=200), AML (n=437), ALL (n=103), non-leukemia hospitalized (n=70,456) admitted to University of Maryland and Johns Hopkins Cancer Centers, and University of Maryland Medical Center. Results: Patients with APL had a significantly higher unadjusted mean and median BMI (32.5 kg/m2 and 30.3 kg/m2) than those with AML (28.3 kg/m2 and 27.1 kg/m2), ALL (29.3 kg/m2 and 27.7 kg/m2), and others (29.3 kg/m2 and 27.7 kg/m2) (p<0.001). Log-transformed BMI multivariable models demonstrated that APL patients had a significantly higher adjusted mean BMI by 3.7 kg/m2 (p<0.001) or approximately 10% (p<0.01) compared to the other groups, when controlled for sex, race, and age. Conclusions: This study confirms that when controlled for sex, age, and race there is an independent association of higher BMI among patients with APL compared to patients with ALL, AML, and hospitalized individuals without leukemia in the same community.

Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens.

PURPOSE: Asparaginases, key agents in treatment of acute lymphoblastic leukemia (ALL), are associated with venous thromboembolism (VTE). While risks of short-acting asparaginase-related VTE is well-known, we studied VTE incidence and risk factors in adult ALL patients treated with and without long-acting pegylated asparaginase (PegA). METHODS: Single-center, retrospective analysis of 89 ALL patients treated with (n = 61) or without (n = 28) PegA at Greenebaum Comprehensive Cancer Center. Reviewed patient and disease characteristics, treatment, and VTE incidence. RESULTS: VTE during treatment occurred in 31 patients (35%), and was associated with PegA (p = 0.001) and Philadelphia chromosome negativity (p = 0.002). Among PegA recipients, VTE was associated with a significantly higher mean body mass index (BMI) of 31.3 kg/m2 (p = 0.037), and was more common with pre-T/T cell compared to pre-B/B cell ALL (68.2% vs. 33.3%, p = 0.009). Antithrombin-III (ATIII) levels were measured for 26 patients; 16 (61.5%) were < 50%. Of those, 8 (50%) experienced VTE, while 3 of 10 (30%) patients with ATIII levels ≥ 50% experienced VTE. VTE occurred in 7 of 13 (54%) of patients who received ATIII repletion. There was a trend toward a higher incidence of VTE in the PegA group among patients with non-O compared to O blood type (55.9% vs. 33.3%, p = 0.079) as well as those with a higher hemoglobin at diagnosis (9.3 vs 8.1 g/dL, p = 0.056). CONCLUSION: This study confirms PegA as a risk factor for VTE in patients with ALL. Risk factors among those receiving PegA include higher BMI and pre-T/T cell ALL. ATIII repletion was not shown to be protective against VTE. There was a higher incidence of VTE in patients who received PegA with non-O compared to O blood type, but the precise correlation is uncertain.

High dose cytarabine, mitoxantrone, pegasapargase (HAM-pegA) in combination with dasatinib for the first-line treatment of Philadelphia chromosome positive mixed phenotype acute leukemia.

The treatment of mixed phenotype acute leukemia (MPAL) is challenging due to the presence of disease characteristics of both myeloid and lymphoid leukemia. Regimens historically used to treat acute lymphoblastic leukemia are often used to treat MPAL, particularly for patients whose diseases also possess the Philadelphia chromosome (Ph+). Here we present a novel regimen, HAM-pegA plus dasatinib, for the treatment of two patients with newly diagnosed Ph+ MPAL. This regimen is a blend of both myeloid-targeted and lymphoid-targeted chemotherapy agents, and is given as a single cycle of intensive chemotherapy followed by oral dasatinib maintenance therapy. Without proceeding to allogeneic transplant, this regimen produced durable remissions of 18 months and longer. This novel regimen offers an exciting alternative to other intensive regimens that require multiple cycles of intensive chemotherapy and allogeneic transplant in first remission.

Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia.

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (p = 0.027). Event-free survival was significantly different in favor of HAM-pegA (p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.

Optimizing pegylated asparaginase use: An institutional guideline for dosing, monitoring, and management.

The incorporation of L-asparaginase and pegylated asparaginase into pediatric-inspired regimens has conferred a survival advantage in treatment of adults with acute lymphoblastic leukemia. Use of asparaginase products requires careful prevention, monitoring, and management of adverse effects including hypersensitivity, hepatotoxicity, pancreatitis, coagulopathy, and thrombosis. Currently, there is limited published literature to offer guidance on management of these toxicities. At the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, a standard of practice guideline was created to prevent and manage asparaginase-related adverse events. By sharing our long-term experience with asparaginase products and clinical management of asparaginase-induced toxicities, this article aims to improve patient safety and optimize treatment outcomes.

Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation.

In the treatment of acute myeloid leukemia (AML), the "7 + 3"-based strategy, combining cytarabine 100-200 mg/m2 for 7 days with an anthracycline for 3 days, remains the standard of care for younger and medically fit patients. Daunorubicin (DNR) and idarubicin (IDA) are the two anthracyclines most commonly used. DNR and IDA are used interchangeably with different conversion factors, as there is no high-level evidence on the equipotency of these two agents for AML treatment. To determine the equipotent doses of DNR and IDA, we first systematically reviewed studies directly comparing the clinical outcomes of AML induction therapy utilizing DNR and IDA. We found 15 articles that met our inclusion criteria and compared time-to-event survival end points as well as complete remission rates post-induction. The DNR:IDA equipotency ratio was estimated at 5.90 with 95% confidence interval (CI) 1.7-20.7. To validate the estimate from our meta-analysis biologically, we conducted in vitro tests comparing anti-AML activity of DNR and IDA against six AML cell lines and two primary AML cells from patients with different cytogenetic and molecular characteristics. Based on these in vitro data, the equipotency dose ratio between DNR and IDA was 4.06 with 95% CI 3.64-4.49. Combining the estimates from the meta-analysis and the in vitro data using inverse-variance weighting, the current best estimate of the DNR:IDA equipotent ratio is 4.1 with 95% CI 3.9-4.3. This estimate, however, is largely driven by the in vitro chemo-sensitivity data. Given clinical studies demonstrating the safety of IDA at higher doses, our work implies that dose intensification of IDA could be investigated in future clinical trials in AML.

A Retrospective Analysis of Prolonged Empiric Antibiotic Therapy for Pneumonia Among Adult Neurocritical Care Patients.

BACKGROUND AND PURPOSE: Current literature reports that half of critically ill patients are continued on broad-spectrum antibiotics beyond 72 hours despite no confirmed infection. The purpose of this retrospective study was to identify the incidence of and risk factors for prolonged empiric antimicrobial therapy (PEAT) in adult neurocritical care (NCC) patients treated for pneumonia, hypothesizing that NCC patients will have a higher incidence of PEAT. METHODS: This is a retrospective chart review of adult NCC patients treated for pneumonia. Antibiotic therapy was classified as restrictive, definitive, or PEAT based on culture results and timing of discontinuation or de-escalation. RESULTS: A total of 95 patients (median age: 57 years; 28.4% female; admission diagnosis: 73.7% cerebrovascular, 10.5% neuromuscular, and 15.8% seizure-related) were included in this study. Overall, 59% of antibiotic regimens were considered PEAT, with vancomycin and piperacillin/tazobactam being most commonly prescribed. Median duration of therapy was 6.8 days, with shorter duration in patients with negative culture results compared to those with positive culture results (6.1 days [interquartile range, IQR 4.0-8.3] vs 7.2 days [IQR 5.8-10.3], P < .05). On multivariable analysis, elevated baseline white blood cell count, meeting Centers for Disease Control criteria for pneumonia, and negative bacterial culture were significantly associated with PEAT. CONCLUSION: The incidence of prolonged empiric antibiotic use was high in the NCC population. Patients are at particular risk for PEAT if they have negative cultures. All but one patient did not meet criteria for central fever, highlighting the challenges in identifying fever etiology in the NCC population.

Addressing Administration Challenges Associated With Blinatumomab Infusions: A Multidisciplinary Approach.

Blinatumomab has shown great potential for patients with chemotherapy-resistant B-cell acute lymphocytic leukemia. Blinatumomab's toxicity profile includes central nervous system toxicities, as well as cytokine release syndrome. Although neurological toxicities associated with blinatumomab are almost always reversible, early detection and intervention of these toxicities is vital to ensure that patients continue their full course of treatment. Guidelines for the preparation and administration of blinatumomab in both inpatient and outpatient settings, as well as a standardized neurological nursing assessment, were developed to ensure safe and effective administration of blinatumomab.

Comparison of prescribing patterns between United States and Dominican Republic prescribers on short-term medical mission trips.

Background: Short-term medical missions (STMMs) have increased and are viewed as a way to extend care in low- and middle-income countries (LMICs). Although benefits may exist, visiting teams may lack insight into using medications safely and effectively. The primary objective was to assess prescribing differences between US-based and Dominican Republic (DR) healthcare providers on STMMs in the DR. Methods: A retrospective database review between January 2013 and 2015 was conducted. Data from US and DR groups were compared for differences in diagnoses, medication classes prescribed and prescriptions per patient. Results: The mean number of medical conditions diagnosed per patient in the DR (n=423) and US groups (n=1585) were 1.4±0.9 and 1.0±0.8, respectively. The diagnosis of infectious diseases was the same as non-communicable diseases. The DR group prescribed more medications at each patient encounter (mean 2.6 vs 2.2, respectively; p<0.001). The US group prescribed more antibiotics for respiratory infections (US 46.2% vs DR 25.0%; p=0.0001), used more metronidazole than albendazole alone for parasite infections (p=0.0022) and used more oral fluconazole for vaginal candidiasis (p<0.0001) and tinea infections (US 44.6%, DR 14.3%, respectively; p=0.0020). Conclusions: Although some significant prescribing differences exist between US and DR providers, many similarities were present. Visiting providers should understand the medication use system and disease burden before providing care in an LMIC.