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.
Primary myelofibrosis (PMF) is characterized by megakaryocyte hyperplasia, dysplasia and death with progressive reticulin/collagen fibrosis in marrow and hematopoiesis in extramedullary sites. The mechanism of fibrosis was investigated by comparing TGF-β1 signaling of marrow and spleen of patients with PMF and of non-diseased individuals. Expression of 39 (23 up-regulated and 16 down-regulated) and 38 (8 up-regulated and 30 down-regulated) TGF-β1 signaling genes was altered in the marrow and spleen of PMF patients, respectively. Abnormalities included genes of TGF-β1 signaling, cell cycling and abnormal in chronic myeloid leukemia (EVI1 and p21(CIP)) (both marrow and spleen) and Hedgehog (marrow only) and p53 (spleen only) signaling. Pathway analyses of these alterations predict an increased osteoblast differentiation, ineffective hematopoiesis and fibrosis driven by non-canonical TGF-β1 signaling in marrow and increased proliferation and defective DNA repair in spleen. Since activation of non-canonical TGF-β1 signaling is associated with fibrosis in autoimmune diseases, the hypothesis that fibrosis in PMF results from an autoimmune process triggered by dead megakaryocytes was tested by determining that PMF patients expressed plasma levels of mitochondrial DNA and anti-mitochondrial antibodies greater than normal controls. These data identify autoimmunity as a possible cause of marrow fibrosis in PMF.
Hairy cell leukaemia-variant (HCL-V) is a rare B-cell malignancy that affects elderly males and manifests with splenomegaly, lymphocytosis and cytopenias without monocytopenia. The neoplastic cells have morphological features of prolymphocytes and hairy cells. The immunophenotype is that of a clonal B-cell CD11c and CD103 positive but, unlike classical HCL, CD25, CD123 and CD200 negative. The spleen histology is similar to classical HCL and the pattern of bone marrow infiltration is interstitial and/or intrasinusoidal. Mutations of the immunoglobulin heavy chain (IGVH) are seen in two thirds of cases with a preferential VH4-34 family usage. There is no distinct chromosomal abnormality but del17p13 and mutations of the TP53 gene are frequent. Mutations in the MAP2K1 gene have been documented in half of the cases. The course is chronic with median survivals of 7-9 years. Patients are refractory to purine analogues and the most effective therapy is the combination of 2-chlorodeoxyadenosine and Rituximab.
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.