A 63-year-old man presented with a 6-month history of fatigue, weight loss, and gingival bleeding. Physical examination suggested the presence of a massively enlarged spleen, a finding confirmed on a reconstructed coronal CT image of the abdomen.
Recombinant IFN-α (rIFN-α) induces complete hematologic remissions in patients with myeloproliferative neoplasms (MPNs), but its use has been limited by side effects owing to the relatively high doses used. Now, low-dose rIFN-α is stressed, starting relatively early in the course of the MPNs. In polycythemia vera, this has resulted in a significant clinical, hematologic, morphologic and molecular response manifested by reduction in the JAK2(V617F) allele burden, sustained even after discontinuation of recombinant IFN. In essential thrombocythemia, platelet count reduction is prompt and durable without treatment for varying periods. In hypercellular primary myelofibrosis, rIFN-α has restored normal blood counts, reduced splenomegaly and induced morphologic marrow remissions. This article highlights our current use of rIFN-α in MPNs.
We sought to investigate the perioperative inflammatory response and immunological function of patients with portal hypertension-induced splenomegaly who underwent laparoscopic (LS) or open splenectomy (OS).
BACKGROUND: Primary myelofibrosis is a myeloproliferative disorder characterized by bone marrow fibrosis, abnormal cytokine expression, splenomegaly and anemia. The activation of JAK2 and the increased levels of circulating proinflammatory cytokines seem to play an important role in the pathogenesis of myelofibrosis. Novel therapeutic agents targeting JAKs have been developed for the treatment of myeloproliferative disorders. Ruxolitinib (INCB018424) is the most recent among them. CASE PRESENTATION: To our knowledge, there is no evidence from clinical trials of an increased risk of tuberculosis during treatment with JAK inhibitors. Here we describe the first case of tuberculosis in a patient treated with Ruxolitinib, a male with a 12-year history of chronic idiopathic myelofibrosis admitted to our Institute because of fever, night sweats, weight loss and an enlarging mass in the left inguinal area for two months. CONCLUSION: Treatment with Ruxolitinib may have triggered the reactivation of latent tuberculosis because of an inhibition of Th1 response. Our case highlights the importance of an accurate screening for latent tuberculosis before starting an anti-JAK 2 treatment.
Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.
There are 7 designated conditions under the category of myeloproliferative neoplasms (MPN), including chronic myelogenous leukemia (CML) and classical MPN, that is, polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF). Recently, reports about Philadelphia and JAK2 V617F-positive MPN cases have been described in literature. The coexistence of different molecular defects may change the clinical and laboratory manifestation of MPN and may result in an inappropriate interpretation of the response to treatment with tyrosine kinase inhibitors in CML patients.
Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA).
Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR or MPL mutation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and shortened survival.
Myelofibrosis is a chronic myeloproliferative neoplasm characterised by splenomegaly, cytopenias, bone marrow fibrosis, and debilitating symptoms including fatigue, weight loss, and bone pain. Mutations in Janus kinase-2 (JAK2) occur in approximately 50% of patients. The only approved JAK2 inhibitor for myelofibrosis is the dual JAK1 and JAK2 inhibitor, ruxolitinib. 58-71% of patients treated with ruxolitinib in clinical trials so far have not achieved the primary endpoint of 35% or more reduction in spleen volume from baseline assessed by MRI or CT. Furthermore, more than 50% of patients discontinue ruxolitinib treatment after 3-5 years. On the basis of this unmet need, we investigated the efficacy and safety of fedratinib, a JAK2-selective inhibitor, in patients with ruxolitinib-resistant or ruxolitinib-intolerant myelofibrosis.
Pacritinib (SB1518) is a JAK2, JAK2(V617F) and FLT3 kinase inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies, or were newly diagnosed with intermediate- or high-risk Lille Score. Patients with any degree of thrombocytopenia, anemia or neutropenia were eligible. Thirty-five patients were enrolled and treated with pacritinib. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100,000/µL. Up to week 24, 8/26 (31%) evaluable patients achieved ≥ 35% decrease in MRI-determined spleen volume and 14/33 (42%) attained ≥ 50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1-2 diarrhea (69%) and nausea (49%) were the most common treatment emergent adverse events, but caused only one treatment discontinuation. Study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). This study supports pacritinib as an active agent in patients with MF, offering a potential treatment option for patients with pre-existing anemia and thrombocytopenia. This trial is registered at www.clinicaltrials.gov as #NCT00745550.