Outcomes of Fedratinib in Routine Treatment of Ruxolitinib-Resistant or -Refractory Patients with Primary and Post-Polycythemia Vera or Essential Thrombocythemia Myelofibrosis: A Nationwide Retrospective Study.

Introduction: In recent years, fedratinib, a selective JAK2 inhibitor, has emerged as a potential therapeutic option for patients who have failed or are intolerant to ruxolitinib. Despite the promising results observed in clinical studies, real-world evidence from the USA and Europe suggests that the efficacy of fedratinib may be less conclusive. We report the characteristics, treatment patterns, and clinical outcomes of patients with myelofibrosis (MF) treated with fedratinib following ruxolitinib failure in Israel's clinical practice.

A phase 2 study of ibrutinib maintenance following first-line high-dose methotrexate-based chemotherapy for elderly patients with primary central nervous system lymphoma.

Background: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression-free survival (PFS) of 6-16 months. Ibrutinib penetrates the blood-brain barrier and has shown activity in PCNSL.

Leukemic Phase of Histiocytic Sarcoma of the Digestive System: A Rare Manifestation of a Rare Disease.

Histiocytic sarcoma (HS) is a rare, malignant, and aggressive subtype of histiocytosis. We present an unusual case of aggressive HS presenting in the gastrointestinal tract and gallbladder that progressed after several lines of chemotherapy with a leukemic phase. We review the clinical, pathological, and molecular characteristics of HS in this case and review the literature on HS involving the digestive system as well as on overt leukemic phase of this disease.

Lenalidomide maintenance for diffuse large B-cell lymphoma patients responding to R-CHOP: quality of life, dosing, and safety results from the randomised controlled REMARC study.

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.

Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

Purpose The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction.

Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis.

Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values.

Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients.

Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.

Hodgkin lymphoma and hypothermia: case report and review of the literature.

We report the development of hypothermia in a patient with Hodgkin lymphoma which resolved with chemotherapy administration. A review of the literature revealed 16 previous reports of hypothermia in patients with Hodgkin lymphoma. Overall prognosis seems to be unfavorable.

Recent advances in understanding and managing adenosine deaminase and purine nucleoside phosphorylase deficiencies.

Purpose Of The Review: To review the recent advances in the understanding and management of the immune and nonimmune effects of inherited adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies.

Recent Findings: Abnormal thymocyte development and peripheral T-cell activation in ADA-deficient and PNP-deficient patients cause increased susceptibility to infections and immune dysregulation. The impaired purine homeostasis also damages many other cell types and tissues.

Activation of cell cycle arrest and apoptosis by the proto-oncogene Pim-2.

Potent survival effects have been ascribed to the serine/threonine kinase proto-oncogene PIM-2. Elevated levels of PIM-2 are associated with various malignancies. In human cells, a single Pim-2 transcript gives rise mainly to two protein isoforms (34, 41 kDa) that share an identical catalytic site but differ at their N-terminus, due to in-frame alternative translation initiation sites.

Effects of purine nucleoside phosphorylase deficiency on thymocyte development.

Background: Inherited or acquired defects in purine nucleoside phosphorylase (PNP) impair purine metabolism, as well as the survival and function of T lymphocytes. However, the effects of PNP deficiency on thymocyte development are not well known.

Objectives: We sought to study thymocyte development in PNP-deficient (PNP-KO) mice.

Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials.

Background: Follicular lymphoma is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival in patients with follicular lymphoma compared with chemotherapy alone, but data from randomized clinical trials evaluating rituximab maintenance treatment in these patients are limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the overall survival of patients with follicular lymphoma.

Erythropoietin treatment in advanced multiple myeloma is associated with improved immunological functions: could it be beneficial in early disease?

Erythropoietin (Epo) is the main growth regulator of red blood cells, and recombinant human erythropoietin (rHuEpo) is thus used in clinical practice for the treatment of anaemia, primarily in kidney disease and cancer. rHuEpo treatment was found to be associated with prolonged survival of multiple myeloma (MM) patients. This clinical observation was then supported by studies on murine myeloma models.

Mutations in the RNA component of RNase mitochondrial RNA processing might cause Omenn syndrome.

Background: Omenn syndrome is a variant of severe combined immunodeficiency disease, which most prominently presents with erythroderma, eosinophilia, and susceptibility to various pathogens. Mutations in the nucleases of recombination activating genes 1 and 2 (RAG1/RAG2) or Artemis were found in some, but not all, patients with Omenn syndrome. We identified 2 patients who presented with clinical features consistent with Omenn syndrome but had no mutations in RAG or Artemis.

PET-CT imaging of combined brachial and lumbosacral neurolymphomatosis.

Neurolymphomatosis is a rare manifestation of progressive non-Hodgkin's lymphoma. A 44-yr-old man with diffuse large B-cell lymphoma presented with unilateral progressive peripheral sensorimotor neuropathy after the 7th cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. No pathology in the nervous system was evident by computerized tomography (CT), magnetic resonance imaging (MRI) of the head, spinal axis and plexuses and by repeated analysis of cerebrospinal fluid.

Effect of IGF-1 on the balance between autophagy of dysfunctional mitochondria and apoptosis.

Mutations in mitochondrial DNA (mtDNA) cause excessive production of mitochondrial reactive oxygen species (ROS) and shorten animal life span. We examined the mechanisms responsible for removal of mitochondria with deleterious mtDNA mutations by autophagy. Incubation of primary cells and cell lines in the absence of serum promotes autophagy of mitochondria with deleterious mtDNA mutations but spares their normal counterparts.

Fulminant intravascular lymphoma presenting as fever of unknown origin.

Intravascular large cell lymphoma (IVLL) is a rare neoplasm characterized by the proliferation of malignant lymphoid cells within the lumens of small to medium-sized blood vessels. The central nervous system, skin, and endocrine systems are most commonly involved. IVLL may disseminate to the heart, pancreas, liver, spleen, kidneys, and adrenal glands.

Treatment of resistant thrombotic thrombocytopenic purpura with rituximab and cyclophosphamide.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon acquired disease in adults, especially young women, characterized by fever, neurologic manifestations, microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. Treatment with plasmapheresis has increased the survival rate from 10% to greater than 90%. Still, a subset of patients with resistant TTP fail to respond to plasmapheresis or remain dependent on this procedure.

Increased expression of the hPim-2 gene in human chronic lymphocytic leukemia and non-Hodgkin lymphoma.

Pim-1 and Pim-2 are murine proto-oncogenes implicated in lymphomagenesis. The aim of this study was to investigate whether the human Pim-2 (hPim-2) expression is altered in chronic lymphocytic leukemia (B-CLL) and non-Hodgkin's lymphomas (NHL). We analyzed hPim-2 expression in 48 patients with NHL and CLL by quantitative in-situ hybridization, quantitative RT-PCR and FACS analysis.

Platelet function and its clinical significance in the myelodysplastic syndromes.

The current study was aimed at investigating platelet function in MDS and its clinical significance. There were 23 patients with untreated MDS at presentation, including refractory anemia (RA), RA with ringed sideroblasts, RA and excess blasts and chronic myelomonocytic leukemia RAEBt. The mean platelet count was 167.

Ultrastructural features of bone marrow cells from patients with acquired sideroblastic anemia.

The ultrastructural findings of the bone marrow cells from 15 patients with acquired sideroblastic anemia are presented. The red cell precursors from all patients showed the presence of electron-dense material in the mitochondria, representing most probably iron deposits. A great number of these mitochondria were completely destroyed.

Role of MHC class I in immune surveillance of mitochondrial DNA integrity.

Mitochondrial DNA is subject to increased rates of mutations due to its proximity to the source of reactive oxygen species. Here we show that increased MHC class I (MHC I) expression serves to alert the immune system to cells with mitochondrial mutations. MHC I is overexpressed in fibroblasts with mitochondrial dysfunction from patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and in lymphocytes from purine nucleoside phosphorylase-deficient immune-deficient mice with mitochondrial DNA deletions.

Factor(s) released from irradiated B-CLL cells induce apoptosis in leukemic lymphocytes.

Photon irradiation of peripheral blood lymphocytes from 25 patients with untreated B-chronic lymphocytic leukemia (B-CLL) induced an increase in apoptotic response by 270%. No significant increase in apoptosis was observed after irradiation of peripheral blood mononuclear cells from 15 healthy volunteers. Supernatants (sups) derived from irradiated leukemic cells incubated with non-irradiated autologous cells induced a 75% enhancement in number of apoptotic cells, as compared with sups from non-irradiated CLL cells.

[Extensive subcutaneous hemorrhage complicating primary amyloidosis].

Bleeding manifestations are common in patients with primary as well as secondary amyloidosis and have been attributed to different mechanical and metabolic causes. Factor X deficiency has been described in patients with primary amyloidosis, although severe bleeding is not common in these patients. We describe a patient with extensive subcutaneous hematoma, a sign that served as the major indicator assisting us in establishing the diagnosis of primary amyloidosis.