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Tacrolimus is an immunosuppressive drug mainly used to lower the risk of transplant rejection in individuals who are post solid organ or hematopoietic transplantation. It is a macrolide which reduces peptidyl-propyl isomerase activity and inhibits calcineurin, thus inhibiting T-lymphocyte signal transduction and interleukin-2 (IL-2) transcription. It has been associated with Posterior Reversible Encephalopathy Syndrome (PRES), a disease of sudden onset that can present as a host of different symptoms, depending on the affected area of the brain. While infectious causes of encephalopathy must always be entertained, the differential diagnosis should also include PRES in the appropriate context. We report three cases of PRES in patients with acute myeloid leukemia (AML) placed on tacrolimus after receiving a bone marrow transplant (BMT). The focus of this review is to enhance clinical recognition of PRES as it is related to an adverse effect of Tacrolimus in the setting of hematopoietic transplantation.

Breast cancer remains the most common cancer in women in the United States, the second most common cause of cancer death, and the main cause of death in women ages 45 to 55 years. Molecular analyses have shown that breast cancer is divided into several subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] enriched, and basal-like), based on microarray techniques. Patients diagnosed as having breast cancer may undergo adjuvant or neoadjuvant chemotherapy, depending on the tumor size, hormone receptor, HER2/neu status, and desire for breast preservation. Patients with positive estrogen and/or progesterone receptor status benefit from treatment with selective estrogen receptor modulators such as tamoxifen or aromatase inhibitors, based on menopausal status and risk of recurrence. HER2-targeted agents such as trastuzumab and pertuzumab are used in combination with chemotherapy in patients with HER2/neu breast cancer. Triple-negative breast cancer is a unique subtype that lacks specific targets, and its treatment primarily includes chemotherapy. This article reviews the current clinical approaches to the management of patients diagnosed as having breast cancer treated with neoadjuvant and/or adjuvant chemotherapy.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.

Relapsed and or refractory lymphoma poses a challenge to the clinician given the poor outcomes. HDACis show promising clinical activity in patients with relapsed/refractory NHL. Active pursuit of developing newer HDACis and clinical trials using combination therapies that help understand the molecular characteristics and synergistic actions of these agents is warranted. This would help improve efficacy, drug tolerability and expand the horizon of these novel agents.

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7113 Background: Azanucleosides (AZN) remain the mainstay of therapy in myelodysplastic syndrome (MDS). Sequential use of AZNs is common practice given the limited alternatives. The only published experience described 14 patients showing a 28% response with decitabine (DAC) after failure or lack of response to azacitidine (AZA). To investigate the potential benefit of this approach,we reviewed cases of sequential AZN treatment. Methods: Patients who received treatment with both AZNs were identified through the Moffitt Cancer Center MDS database. Two groups were identified; group one who received DAC after AZA failure and group 2, who received AZA after DAC failure. The primary objective was to estimate overall response rates according to the International Working Group (IWG) 2006 criteria. The Kaplan–Meier method was used to estimate median OS. Results: A total of 39 MDS patients were identified who received treatment with both AZNs. Complete records were available in 31 patients, including 21 patients in group 1 (DAC after AZA) and 10 patients in group 2 (AZA after DAC). The Table summarizes baseline characteristics and response rates. The median OS for Group 1 from diagnosis was 48 months and for group 2 was 100 months (p=0.7). Conclusions: Sequential use of AZNs after failure of first line may be an effective alternative outside the context of clinical trials. Response rate is higher in patients who receive AZA after DAC. Sequential use of HMA should be considered in context of randomized clinical trial of novel agent as the control arm. [Table: see text]

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