A Primary Extracutaneous Presentation of Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare aggressive cutaneous neuroendocrine malignancy with a mortality rate of around 33%. The presence of advanced disease at the time of diagnosis is associated with poor prognosis. Twofold etiologies have been described in the pathogenesis of Merkel cell carcinoma: chronic exposure to ultraviolet (UV) light and Merkel cell polyomavirus (MCPvY).

A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia.

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV.

Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase.

Myeloproliferative neoplasms (MPN) that have evolved into accelerated or blast phase disease (MPN-AP/BP) have poor outcomes with limited treatment options and therefore represent an urgent unmet need. We have previously demonstrated in a multicenter, phase 1 trial conducted through the Myeloproliferative Neoplasms Research Consortium that the combination of ruxolitinib and decitabine is safe and tolerable and is associated with a favorable overall survival (OS). In this phase 2 trial, 25 patients with MPN-AP/BP were treated at the recommended phase 2 dose of ruxolitinib 25 mg twice daily for the induction cycle followed by 10 mg twice daily for subsequent cycles in combination with decitabine 20 mg/m2 for 5 consecutive days in a 28-day cycle.

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea.

Prior studies have reported high response rates with recombinant interferon-α (rIFN-α) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-α, we investigated the outcomes of pegylated-rIFN-α2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PV who were either refractory or intolerant to HU.

Ruxolitinib Therapy Followed by Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation for Myelofibrosis: Myeloproliferative Disorders Research Consortium 114 Study.

We evaluated the feasibility of ruxolitinib therapy followed by a reduced-intensity conditioning (RIC) regimen for patients with myelofibrosis (MF) undergoing transplantation in a 2-stage Simon phase II trial. The aims were to decrease the incidence of graft failure (GF) and nonrelapse mortality (NRM) compared with data from the previous Myeloproliferative Disorders Research Consortium 101 Study. The plan was to enroll 11 patients each in related donor (RD) and unrelated donor (URD) arms, with trial termination if ≥3 failures (GF or death by day +100 post-transplant) occurred in the RD arm or ≥6 failures occurred in the URD.

A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.

CPI-613, a lipoate analogue that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH), has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response and determined the MTD, efficacy, and safety of CPI-613 combined with high-dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models.

Outcomes and changes in code status of patients with acute myeloid leukemia undergoing induction chemotherapy who were transferred to the intensive care unit.

Patients with Acute Myeloid Leukemia (AML) have compromised marrow function and chemotherapy causes further suppression. As a result complications are frequent, and patients may require admission to the intensive care unit (ICU). How codes status changes when these events occur and how those changes influence outcome are largely unknown.

Effect of Intensive Chemotherapy on Physical, Cognitive, and Emotional Health of Older Adults with Acute Myeloid Leukemia.

Objectives: To measure short-term changes in physical and cognitive function and emotional well-being of older adults receiving intensive chemotherapy for acute myeloid leukemia (AML).

Design: Prospective observational study.

Setting: Single academic institution.

Polycythemia Vera: An Appraisal of the Biology and Management 10 Years After the Discovery of JAK2 V617F.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with a substantial symptom burden, thrombohemorrhagic complications, and impaired survival. A decade after the seminal discovery of an activating mutation in the tyrosine kinase JAK2 in nearly all patients with PV, new treatment options are finally beginning to emerge, necessitating a critical reappraisal of the underlying pathogenesis and therapeutic modalities available for PV. Herein, we comprehensively review clinical aspects of PV including diagnostic considerations, natural history, and risk factors for thrombosis.

High dose cytarabine, mitoxantrone and l-asparaginase (HAMA) salvage for relapsed or refractory acute myeloid leukemia (AML) in the elderly.

Acute myeloid leukemia (AML) is an aggressive malignancy that affects older patients. The role of salvage therapy in the elderly is controversial and there is little data on efficacy. Outcomes for 94 relapsed or refractory AML patients who received salvage HAMA therapy were analyzed.

CD138-negative myeloma cells regulate mechanical properties of bone marrow stromal cells through SDF-1/CXCR4/AKT signaling pathway.

As the second most prevalent hematologic malignancy, multiple myeloma (MM) remains incurable and relapses due to intrinsic or acquired drug resistance. Therefore, new therapeutic strategies that target molecular mechanisms responsible for drug resistance are attractive. Interactions of tumor cells with their surrounding microenvironment impact tumor initiation, progression and metastasis, as well as patient prognosis.

Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML).

The hypomethylating agents (HAs), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with acute myeloid leukemia (AML). Little is known about how AML responds to hypomethylating agents after standard therapy, and the activity of these agents in a real-world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002 to 2011 treated with HAs either as first-line (n = 34), salvage (n = 28), or consolidation (n = 13) therapy.

The survival of memory CD8 T cells that is mediated by IL-15 correlates with sustained protection against malaria.

Ag-specific memory T cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. Studies of protective immunity among residents of malaria endemic areas indicate that memory responses to Plasmodium Ags are not adequately developed or maintained, as people who survive episodes of childhood malaria are still vulnerable to either persistent or intermittent malaria infections. In contrast, multiple exposures to radiation-attenuated Plasmodium berghei sporozoites (Pb γ-spz) induce long-lasting protective immunity to experimental sporozoite challenge.

Chromatin-modifying agents promote the ex vivo production of functional human erythroid progenitor cells.

Presently, blood transfusion products (TPs) are composed of terminally differentiated cells with a finite life span. We have developed an ex vivo-generated TP composed of erythroid progenitor cells (EPCs) and precursors cells. Several histone deacetylase inhibitors (HDACIs) were used in vitro to promote the preferential differentiation of cord blood (CB) CD34(+) cells to EPCs.

Treatment with the Bcl-xL inhibitor ABT-737 in combination with interferon α specifically targets JAK2V617F-positive polycythemia vera hematopoietic progenitor cells.

Polycythemia vera (PV) treatment with interferon α (IFNα) is frequently limited by dose-related toxicity. PV CD34(+) cells are characterized by overexpression of Bcl-xL, which can be antagonized by ABT-737 leading to apoptosis. We explored the effects of ABT-737 and IFNα on PV hematopoiesis.

Interferon-alpha targets JAK2V617F-positive hematopoietic progenitor cells and acts through the p38 MAPK pathway.

Objective: Interferon-alpha (IFNalpha) therapy leads to hematological remissions and a reduction of the JAK2V617F allele burden in patients with polycythemia vera (PV). In this study, the cellular target by which IFNalpha affects hematopoiesis in PV patients was evaluated.

Materials And Methods: CD34(+) cells were isolated from normal bone marrow and the peripheral blood of patients with PV and were treated in vitro with each of the three commercially available forms of IFNalpha: IFNalpha 2b, pegylated IFNalpha 2a (Peg-IFNalpha 2a), and pegylated IFNalpha 2b (Peg-IFNalpha 2b).

The immune status of Kupffer cells profoundly influences their responses to infectious Plasmodium berghei sporozoites.

Multi-factorial immune mechanisms underlie protection induced with radiation-attenuated Plasmodia sporozoites (gamma-spz). Spz pass through Kupffer cells (KC) before invading hepatocytes but the involvement of KC in protection is poorly understood. In this study we investigated whether gamma-spz-immune KC respond to infectious spz in a manner that is distinct from the response of naive KC to infectious spz.

Protracted protection to Plasmodium berghei malaria is linked to functionally and phenotypically heterogeneous liver memory CD8+ T cells.

We previously demonstrated that protection induced by radiation-attenuated (gamma) Plasmodium berghei sporozoites is linked to MHC class I-restricted CD8(+) T cells specific for exoerythrocytic-stage Ags, and that activated intrahepatic memory CD8(+) T cells are associated with protracted protection. In this study, we further investigated intrahepatic memory CD8(+) T cells to elucidate mechanisms required for their maintenance. Using phenotypic markers indicative of activation (CD44, CD45RB), migration (CD62L), and IFN-gamma production, we identified two subsets of intrahepatic memory CD8(+) T cells: the CD44(high)CD45RB(low)CD62L(low)CD122(low) phenotype, representing the dominant effector memory set, and the CD44(high)CD45RB(high)CD62L(low/high)CD122(high) phenotype, representing the central memory set.