Acute myeloid leukemia cutis with KMT2A::MLLT3 fusion presenting with leonine facies.

A 63-year-old woman presented with plaques covering 60 % body-surface-area and leonine facies. Blood work showed no diagnostic aberrancies. Skin biopsy contained a malignant CD4+/CD56+ mononuclear cell population concerning for blastic plasmacytoid dendritic cell neoplasm. A later bone marrow biopsy confirmed AML with KMT2A::MLLT10 fusion detected by next-generation sequencing (NGS). This patient's LC preceded blood and marrow based symptoms of AML. NGS of the initial skin biopsy should be considered as part of diagnostic guidelines in cases with LC in the differential as this may have led to earlier diagnosis in this case and future cases.

A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents.

Patients with myelodysplastic syndromes/neoplasms (MDS) or acute myeloid leukemia (AML) with hypomethylating agent failure have a poor prognosis. Myeloid-derived suppressor cells (MDSCs) can contribute to MDS progression and mediate resistance to anti-PD1 therapy. As histone deacetylase inhibitors (HDACi) decrease MDSCs in preclinical models, we conducted an investigator-initiated, NCI-Cancer Therapy Evaluation Program-sponsored, multicenter, dose escalation, and expansion phase Ib trial (NCT02936752) of the HDACi entinostat and the anti-PD1 antibody pembrolizumab. Twenty-eight patients (25 MDS and 3 AML) were enrolled. During dose escalation (n=13 patients), there was one dose-limiting toxicity (DLT) on dose level (DL) 1 (G5 pneumonia/bronchoalveolar hemorrhage) and two DLTs at DL 2 (G3 pharyngeal mucositis and G3 anorexia). Per the 3 + 3 dose escalation design, DL 1 (entinostat 8 mg PO days 1 and 15 + pembrolizumab 200 mg IV day 1 every 21 days) was expanded and another 15 patients were enrolled. Hematologic adverse events (AEs) were common. The most common non-hematologic ≥G3 AEs were infection (32%), hypoxia/respiratory failure (11%), and dyspnea (11%). There were no protocol-defined responses among the 28 patients enrolled. Two patients achieved a marrow complete remission (mCR). Using a systems immunology approach with mass cytometry and machine learning analysis, mCR patients had increased classical monocytes and macrophages but there was no significant change of MDSCs. In conclusion, combining entinostat with pembrolizumab in patients with advanced MDS and AML was associated with limited clinical efficacy and substantial toxicity. Absence of an effect on MDSCs could be a potential explanation for the limited efficacy of this combination. ClinicalTrial.gov Identifier: NCT02936752.

Systemic coagulation is activated in patients with meningioma and glioblastoma.

PURPOSE: Up to 30% of patients with glioblastoma (GBM) develop venous thromboembolism (VTE) over the course of the disease. Although not as high, the risk for VTE is also increased in patients with meningioma. Direct measurement of peak thrombin generation (TG) allows quantitative assessment of systemic coagulation activation in patients with GBM and meningioma. Our aim was to determine the extent of systemic coagulation activation induced by brain tumors, to measure the shift between pre- and post-operative peak TG in patients with GBM, and to assess the relationship between pre-surgical peak TG and pre-operative brain tumor volume on imaging. METHODS: Pre- and post-surgical plasma samples were obtained from successive patients with GBM and once from patients with meningioma and healthy age- and sex-matched blood donor controls. TG was measured using the calibrated automated thrombogram (CAT) assay, and tumor volumes were measured in pre-surgical MRI scans. RESULTS: Pre-surgical peak TG was higher in patients with GBM than in controls (288.6 ± 54.1 nM vs 187.1 ± 41.7 nM, respectively, P < 0.001), and, in the nine patients with GBM and paired data available, peak TG was significantly reduced after surgery (323 ± 38 nM vs 265 ± 52 nM, respectively, P = 0.007). Similarly, subjects with meningioma demonstrated higher peak TG compared to controls (242.2 ± 54.9 nM vs 177.7 ± 57.0 nM, respectively, P < 0.001). There was no association between peak TG and pre-operative tumor volume or overall survival. CONCLUSION: Our results indicate that systemic coagulation activation occurs with both meningioma and GBM, but to a greater degree in the latter. Preoperative peak TG did not correlate with tumor volume, but removal of GBM caused a significant decrease in coagulation activation.

Acute myeloid leukemia with hepatic infiltration presenting as obstructive jaundice.

We present the case of a 55-year-old woman who presented with laboratory studies concerning for acute myeloid leukemia (AML) as well as obstructive cholestasis. In similar previously reported cases, concerns of chemotherapy toxicity exacerbated by liver dysfunction or concerns of untreated, concurrent cholecystitis in a neutropenic patient often delay initiation of chemotherapy for full medical workup. At admission, our patient was started on the cytoreductive agent hydroxyurea. By day 10 of her medical workup, her liver function had improved with total bilirubin levels normalizing. At that time, full-dose 7 + 3 induction with cytarabine and daunorubicin was then initiated.

Extracorporeal photopheresis for graft versus host disease: Identifying a clinical pathway and associated resource utilization.

Extracorporeal photopheresis (ECP) is an established therapy for the treatment of graft-versus-host-disease (GVHD) following an allogeneic stem cell transplant. We performed a prospective analysis of patients receiving ECP treatment for GVHD to identify a clinical pathway and resource utilization of this process. The cohort included consecutive allogeneic stem cell recipients with GVHD. ECP was performed using the CELLEX Photopheresis System or the UVAR XTS Photopheresis System (Therakos, Inc, Exton, PA). A clinical pathway was developed and a time and motion study was conducted to define the resource utilization and costs associated with ECP. Patients were treated with either CELLEX (n = 18 procedures) or UVAR (n = 4 procedures). Total time commitment for each procedure for the 2 machines differed. The time for ECP was 117 min (median, range: 91-164 min) using CELLEX and 161 min (median; range: 140-210) using the UVAR-XTS machine. Total costs of each ECP procedure were $3420.50. There is a considerable time commitment of the patient and the clinical staff when employing ECP to treat GVHD. ECP costs are significant considering this is a prolonged therapy continued for several months. With this finalized pathway and costs, we have a standardized clinical pathway for the treatment of GVHD. We are addressing minimizing resource utilization while emphasizing quality care for these patients.

Successful use of cryocrit for monitoring response to therapeutic plasma exchange in type 1 cryoglobulinemia.

Waldenstrom macroglobulinemia (WM) is a clinical syndrome that is defined as lymphoplasmacytic lymphoma with bone marrow involvement and IgM monoclonal gammopathy of any level. In some instances WM can result in a type I cryoglobulinemia with very high cryocrits, which is unusual in type II and III cryoglobulinemia. We describe a case of an 80 year old male with WM, severe type I cryoglobulinemia, and an extremely elevated cryocrit (69%). Over the course of five weeks we performed nine therapeutic plasma exchanges (TPE), and after seven treatments his cryocrit had decreased to 6% with improvement in his symptoms. By monitoring his cryocrit throughout his TPE sessions, we were able to assess his response to treatment, determine the ideal length of treatment in addition to his symptomatic improvement. J. Clin. Apheresis 31:403-404, 2016. © 2015 Wiley Periodicals, Inc.

Significant reduction in red blood cell transfusions in a general hospital after successful implementation of a restrictive transfusion policy supported by prospective computerized order auditing.

BACKGROUND: Our hospital transfusion policy was recently revised to recommend single-unit red blood cell transfusion (RBC TXN) for nonbleeding inpatients when the hemoglobin (Hb) level is not more than 7 g/dL. Our computerized provider order entry system was reconfigured to provide real-time decision support using prospective computerized order auditing based on the most recent Hb level and to remove the single-click ordering option for 2-unit RBC TXNs to enhance compliance. This study was undertaken to assess the impact of these changes on hospital transfusion practice. STUDY DESIGN AND METHODS: This study analyzed the total number of transfusion events, proportion of single and 2-unit transfusions and the Hb transfusion trigger in the preimplementation period (October 2011-March 2012) compared to the postimplementation period (October 2012-March 2013). RESULTS: In the postimplementation period the total number of RBC units transfused/1000 patient-days decreased from 60.8 to 44.2 (p < 0.0001). The proportion of 2-unit TXNs decreased from 47% to 15% (p < 0.0001). We also observed significant decreases in pretransfusion Hb triggers. CONCLUSION: Implementation of restrictive transfusion policy supported by prospective computerized order auditing has resulted in significantly decreased RBC utilization at our institution.

The impact of diabetes mellitus on breast cancer outcomes: a single center retrospective study.

Diabetes mellitus has been implicated to affect the prognostic outcomes of patients with various types of cancer. This study explores the impact of diabetes mellitus on the survival outcomes of patients with all stages of breast cancer. We performed a retrospective analysis of 255 patients with all stages of breast cancer. Survival outcomes were compared for diabetic and non-diabetic patients. A greater percent of patients in the non-diabetic group (54.1%) presented with early-stage (stage 0 and 1) cancer than diabetics for which 41.2% presented with stage 0 or 1 breast cancer; however this difference did not achieve statistical significance (p = 0.068). Overall, we observed a significant difference in survival between the diabetics and non-diabetic subjects (p = 0.001). Even after adjustment for all covariates and after stratification for Body Mass Index (BMI), diabetics were found to have a poorer prognosis in terms of survival time. In patients with breast cancer, diabetes mellitus is an independent predictor of lower overall survival rates, even after adjusting for other comorbidities. Primary caregivers and oncologists alike should aggressively screen breast cancer patients for diabetes mellitus and vice versa.

Characteristics of colorectal cancer in the human immunodeficiency virus-infected African American population.

Colorectal Cancer (CRC) is the second leading cause of cancer mortality in the United States. African Americans (AAs) have the highest incidence of CRC of any American ethnic group. Survival from CRC in AAs is lower than in Caucasians, and the mean age of CRC development in AAs is younger. The AA community also has a high rate of HIV infection, accounting for 50.3% of all cases despite making up only 13.6% of the population. This retrospective cohort study identified 17 AA HIV patients with CRC. The patients were matched with 42 HIV-negative CRC patients (controls), based on age, sex, and TNM stage. Data were obtained from 3 hospitals in New Jersey: St. Michael's Medical Center, Trinitas Medical Center and St. Joseph's Medical Center. The age, sex, HIV status, tumor site, stage, drug usage, Hepatitis C status, and survival outcome of subjects and controls were compared. Data from the Surveillance Epidemiology & End Results (SEER) specific to AAs were also compared. The mean age of CRC diagnosis was younger, 50.7 years (median: 52 years, range: 35-71 years), versus 59.42 years (median: 66 years) (P < 0.0001) in the SEER AA population. Of the patients, 29.4% were diagnosed with CRC at less than 45 years of age, versus only 6.35% of the SEER AA population (P < 0.0002). The male-to-female ratio was 11:6. Seven individuals used IV drugs, and 7 had hepatitis C. The mean CD4+ T-cell count was 510.81 cells/mm(3) (median 419). At the time of CRC diagnosis, the average duration of HIV infection was 7.6 years (range 0-22.4 years).Of patients, 87.5% had left-sided CRC, versus 57.55% of the SEER population (P < 0.024). Of the patients, 52.94% had stage III-IV, at diagnosis, versus 43.84% in SEER. There was no statistically significant survival difference between the cases and controls. In our cohort of HIV-infected AA's with CRC, the staging and outcome of CRC did not appear to be affected by the degree of immunosuppression. HIV-infected AA with CRC presented with a higher percentage of left-sided CRC than AA's without HIV. Additionally, AAs with HIV tended to be younger at the time of CRC diagnosis. Our findings suggest that screening for CRC should be offered to HIV-infected AAs before the age of 45, and that sigmoidoscopy with fecal occult blood testing might be an acceptable screening modality. However, the exact age of initiation, optimal frequency, and preferred method of screening (colonoscopy vs. sigmoidoscopy) in this population requires further study.