A retrospective real-world study of the current treatment pathways for myelofibrosis in the United Kingdom: the REALISM UK study.

Background: Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom.

Methods: The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF.

Case of Kikuchi-Fujimoto disease associated with multiple myeloma.

We present a 47-year-old, South-African origin, woman with a background of stable monoclonal gammopathy of unknown significance (MGUS) who attended A&E with a history of coryzal symptoms associated with persistent fever, lymphadenopathy and a new onset of rash, not responding to antibiotics and paracetamol. A trial of high-dose steroids resolved symptoms. Bone marrow biopsy confirmed a progression of MGUS into multiple myeloma and her axillary lymph node biopsy analysis supported a diagnosis of Kikuchi-Fujimoto disease (KFD).

A novel ultrasound-based approach to investigate extramedullary haematopoiesis in foetal spleen.

Foetal spleen is described as a transient focus of haematopoiesis between the 3 and 5 month of gestation: this function is however entirely replaced by the bone marrow before the end of pregnancy. This study identifies haematopoiesis in foetal spleen by exploring changes of echogenicity during its development throughout gestation. Two intervals of pregnancy were studied: Mid-Pregnancy (Mid-P, 19-23 weeks) and End-Pregnancy (End-P, 37-41 weeks).

GATA-1: A potential novel biomarker for the differentiation of essential thrombocythemia and myelofibrosis.

Essentials The BCR-ABL negative myeloproliferative neoplasms are subjected to unknown phenotypic modifiers. GATA-1 is upregulated in ET patients, regardless of treatment regimen or mutational status. Myelofibrosis (MF) megakaryocytes displayed decreased GATA-1 staining.

The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF).

The randomized, double-blind, double-dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)-related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV-related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm -symptom assessment form total symptom score cytokine symptom cluster (TSS-C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs.

Treatment with ipilimumab: a case report of complete response in a metastatic malignant melanoma patient.

Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma.

Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy(®)), a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), as second-line treatment after progression with dacarbazine, for (wild-type BRAF) metastatic melanoma.

BRAF test and cytological diagnosis with a single fine needle cytology sample.

Objective: Recently, fine needle cytology (FNC) of the thyroid has been combined with biomolecular analysis. In particular, there has been detailed study of the V600E-BRAF mutation. The aim of our study is to demonstrate that with a single thyroid sample it is possible to obtain enough cellular material for both cytological diagnosis and a V600E-BRAF molecular test.

A case of abdominal sarcoidosis in a patient with acute myeloid leukemia.

The allogeneic bone marrow transplantation usually preceded by induction chemotherapy, in fit patients, represents the gold standard in the acute myeloid leukaemia. In the last years, many trials have been set up with the view of improving the number of remissions during the induction by adding new drugs. Several early or late side effects have been described in the literature.

A case of small cell carcinoma of the prostate and review of the literature.

Aim And Background: Small cell carcinoma of the prostate (SCCP) is a relatively rare entity, an aggressive tumor with a tendency to metastasize early. There is no standard chemotherapy regimen for SCCP. We report the case of a 67-year-old man with an initial diagnosis of prostate adenocarcinoma with bone metastases who subsequently developed a small cell carcinoma of the prostate with liver metastases.

Preferential nuclear accumulation of JAK2V617F in CD34+ but not in granulocytic, megakaryocytic, or erythroid cells of patients with Philadelphia-negative myeloproliferative neoplasia.

Recently, Dawson et al identified a previously unrecognized nuclear role of JAK2 in the phosphorylation of histone H3 in hematopoietic cell lines. We searched nuclear JAK2 in total bone marrow (BM) cells and in 4 sorted BM cell populations (CD34(+), CD15(+), CD41(+), and CD71(+)) of 10 myeloproliferative neoplasia (MPN) patients with JAK2V617F mutation and 5 patients with wild-type JAK2 MPN. Confocal immunofluorescent images and Western blot analyses of nuclear and cytoplasmic fractions found nuclear JAK2 in CD34(+) cells of 10 of 10 JAK2-mutated patients but not in patients with wild-type JAK2.

EVI1 Impairs myelopoiesis by deregulation of PU.1 function.

EVI1 is an oncogene inappropriately expressed in the bone marrow (BM) of approximately 10% of myelodysplastic syndrome (MDS) patients. This disease is characterized by severe anemia and multilineage myeloid dysplasia that are thought to be a major cause of mortality in MDS patients. We earlier reported on a mouse model that constitutive expression of EVI1 in the BM led to fatal anemia and myeloid dysplasia, as observed in MDS patients, and we subsequently showed that EVI1 interaction with GATA1 blocks proper erythropoiesis.

Consistent up-regulation of Stat3 Independently of Jak2 mutations in a new murine model of essential thrombocythemia.

Janus-activated kinase 2 (JAK2) mutations are common in myeloproliferative disorders; however, although they are detected in virtually all polycythemia vera patients, they are found in approximately 50% of essential thrombocythemia (ET) patients, suggesting that converging pathways/abnormalities underlie the onset of ET. Recently, the chromosomal translocation 3;21, leading to the fusion gene AML1/MDS1/EVI1 (AME), was observed in an ET patient. After we forced the expression of AME in the bone marrow (BM) of C57BL/6J mice, all the reconstituted mice died of a disease with symptoms similar to ET with a latency of 8 to 16 months.

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients.

A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61).

A methodology to study the deformability of red blood cells flowing in microcapillaries in vitro.

The deformability of red blood cells flowing in microvessels is essential to maintain optimal blood circulation and to allow gas transfer between blood and tissues. Here, we report on an experimental methodology to investigate the deformability of RBCs flowing in microcapillaries having diameter close to the average cell size. The microcapillaries are placed in a rectangular flow cell, where a suspension of RBCs, properly diluted in albumin-additioned ACD, is fed through a syringe under the action of a liquid head in the physiological range.

Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis.

Recurring chromosomal translocations observed in human leukemia often result in the expression of fusion proteins that are DNA-binding transcription factors. These altered proteins acquire new dimerization properties that result in the assembly of inappropriate multimeric transcription complexes that deregulate hematopoietic programs and induce leukemogenesis. Recently, we reported that the fusion protein AML1/MDS1/EVI1 (AME), a product of a t(3;21)(q26;q22) associated with chronic myelogenous leukemia and acute myelogenous leukemia, displays a complex pattern of self-interaction.

RUNX1-RUNX1 homodimerization modulates RUNX1 activity and function.

RUNX1 (AML1, CBFalpha2, PEBP2alphaB) is a transcription factor essential for the establishment of the hematopoietic stem cell. It is generally thought that RUNX1 exists as a monomer that regulates hematopoietic differentiation by interacting with tissue-specific factors and its DNA consensus through its N terminus. RUNX1 is frequently altered in human leukemia by gene fusions or point mutations.

Point mutations in two EVI1 Zn fingers abolish EVI1-GATA1 interaction and allow erythroid differentiation of murine bone marrow cells.

EVI1 is an aggressive nuclear oncoprotein deregulated by recurring chromosomal abnormalities in myelodysplastic syndrome (MDS). The expression of the corresponding gene is a very poor prognostic marker for MDS patients and is associated with severe defects of the erythroid lineage. We have recently shown that the constitutive expression of EVI1 in murine bone marrow results in a fatal disease with features characteristic of MDS, including anemia, dyserythropoiesis, and dysmegakaryopoiesis.

Doppler echocardiography during the follow-up of hematological patients undergoing chemotherapy.

Our retrospective experience underscores the ability of Doppler echocardiography to detect the cardiotoxicity of chemotherapy (functional and pericardial abnormalities, heart involvement) and points out the need for an accurate echocardiographic follow-up of hematologic patients.

Intestinal toxicity during induction chemotherapy with cytarabine-based regimens in adult acute myeloid leukemia.

Background: Cytotoxic regimens used in induction treatments for acute myeloid leukemia (AML) almost always include standard or high-dose cytarabine (Ara-C). During or soon after induction therapy, leukemic patients frequently develop gastroenteric complications, characterized by abdominal pain and diarrhea. The association of these symptoms with fever and melena is typical of necrotizing enterocolitis (NE), a life-threatening condition that can be documented by ultrasound abdominal scan.