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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.
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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.
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Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Asparaginasa/efectos adversos , Asparaginasa/farmacología , Escherichia coli/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tromboembolia Venosa/inducido químicamente , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antitrombina III/metabolismo , Linfocitos B/efectos de los fármacos , Índice de Masa Corporal , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Linfocitos T/efectos de los fármacos , Adulto JovenRESUMEN
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.
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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.
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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.
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Antineoplásicos/administración & dosificación , Asparaginasa/administración & dosificación , Instituciones Oncológicas/normas , Manejo de la Enfermedad , Monitoreo de Drogas/normas , Polietilenglicoles/administración & dosificación , Guías de Práctica Clínica como Asunto/normas , Adulto , Antineoplásicos/efectos adversos , Asparaginasa/efectos adversos , Preescolar , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Humanos , Polietilenglicoles/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Trombosis/inducido químicamente , Trombosis/epidemiología , Trombosis/prevención & control , Resultado del TratamientoRESUMEN
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.
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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.