The authors present the case of an infant with severe rickets and secondary myelofibrosis and review the differential diagnosis of hepatosplenomegaly from the viewpoint of the pediatric hematologist/oncologist. [ncbi.nlm.nih.gov]

Case presentation We report a 36-year-old pregnant woman who presented with cytopenia, fatigue, vomiting, and diarrhea for 20 days on the background of newly diagnosed myelofibrosis secondary to gastric signet ring adenocarcinoma. [bmccancer.biomedcentral.com]

• Splenomegaly

  PURPOSE: To evaluate the impact of splenic irradiation as a palliative treatment for symptomatic splenomegaly due to secondary myelofibrosis. [ncbi.nlm.nih.gov]

  Splenectomy may also be necessary if splenomegaly impairs alimentation and should be performed before cachexia sets in. [theoncologyinstitute.com]

• Anemia

  It is recommended that all cancer patients with unexplained anemia and thrombocytopenia be evaluated for the coexistence of bone marrow metastasis and TTP. [ncbi.nlm.nih.gov]

  ) Type 1 Excludes acute myelofibrosis ( C94.4- ) idiopathic myelofibrosis ( D47.1 ) leukoerythroblastic anemia ( D61.82 ) myelofibrosis with myeloid metaplasia ( D47.4 ) myelophthisic anemia ( D61.82 ) myelophthisis ( D61.82 ) primary myelofibrosis [icd10data.com]

  Other possible treatments include blood transfusions, anemia medications, radiation and chemotherapy, or splenectomy (if swelling becomes severe, or to reduce anemia.) [diagnose-me.com]

• Constitutional Symptom

  IMPORTANCE: Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by anemia, splenomegaly, debilitating constitutional symptoms, and shortened survival. [ncbi.nlm.nih.gov]

  Sum the number of adverse prognostic factors Age > 65 y Constitutional symptoms Hemoglobin WBC count > 25 × 10 9 /L Circulating blasts >1% 2. [bloodref.com]

  Glucocorticoids have been used to control constitutional symptoms and autoimmune complications and may ameliorate anemia alone or in combination with low dose thalidomide (50-100 mg/d). [theoncologyinstitute.com]

  Suppression of the secondary, paraneoplastic, chronic inflammatory state in myelofibrosis may improve constitutional symptoms and indirectly control the underlying clonal myeloproliferation. [ascopost.com]

• Asymptomatic

  If someone has asymptomatic myelofibrosis, it is possible that little or no treatment will be needed, other than monitoring the disease and its progression. [bonemarrowmx.com]

  Screening for Hepatitis C | CTFPHC Review Canadian Task Force on Preventive Health Care guideline on Hepatitis C screening REFERENCE BOOK Screening for Abdominal Aortic Aneurysm | CTFPHC REFERENCE BOOK Impaired Vision | CTFPHC REFERENCE BOOK Screening for Asymptomatic [qxmd.com]

  […] collagen fibrosis and osteosclerosis May transform to acute leukemia Characterized by prefibrotic (cellular) and fibrotic stages Etiology Exposure to chemicals such as benzene, ionizing radiation Familial / inherited forms exist Clinical features May be asymptomatic [pathologyoutlines.com]

  Presentation [ 6, 7 ] In early stages, the disease may be asymptomatic. [patient.info]

  Conditions Associated With Myelofibrosis Symptoms and Signs In many patients, myelofibrosis is asymptomatic. Other patients have symptoms of anemia, splenomegaly, or, in later stages, general malaise, weight loss, fever, or splenic infarction. [merckmanuals.com]

• Congestive Heart Failure

  heart failure and acute leukemia Diagnosis Need 3 major and 2 minor criteria for diagnosis of primary myelofibrosis (PMF) Major criteria: Megakaryocyte proliferation and atypia, often with reticulin or collagen fibrosis OR in absence of fibrosis Megakaryocyte [pathologyoutlines.com]

  heart failure). 11, 21 Low-risk patients may be treated with phlebotomy alone. [clevelandclinicmeded.com]

• Gaucher Disease

  […] various pathological processes that involve the bone marrow Causes of secondary myelofibrosis: Neoplastic – infiltration by cancer cells (primary is usually located in breast, lung or prostate) Infective – tuberculosis, fungal infections, HIV Metabolic – Gaucher [pgblazer.com]

• Pneumonia

  Overall, there were 14 severe adverse events in 5 study patients, including 3 deaths, 2 from pneumonia and 1 from progressive multi-organ failure. [raredr.com]

  The most commonly reported adverse events with Jakafi at any time were thrombocytopenia, anemia, diarrhea, and peripheral edema; grade 3/4 adverse events included anemia, thrombocytopenia, pneumonia, general physical health deterioration, and dyspnea. [curetoday.com]

  The child had bilateral pneumonia and significant hepatosplenomegaly (liver 4 cms and spleen 3 cms below the Costa! margin). There were no neurological abnormalities except for a mild generalized hypotonia. [jpma.org.pk]

  Infections, commonly pneumonia, may occur as a result of immune deficiency. Leukaemic transformation to acute myeloid leukaemia may occur. [patient.info]

  […] pain Bruising and easy bleeding due to inadequate numbers of platelets Cachexia (loss of appetite, weight loss, and fatigue) Enlargement of both the liver and spleen Fatigue Gout and high uric acid levels Increased susceptibility to infection, such as pneumonia [en.wikipedia.org]

• Early Satiety

  Signs and symptoms that may develop as MF progresses include anemia, which contributes to feelings of fatigue and weakness; fullness or bloating in the left upper abdominal area, or feeling full after eating a small amount of food (early satiety) that [mpninfo.org]

  The spleen continues to enlarge which leads to early satiety painful episodes of splenic infarction may occur. 5. 5 MYELOFIBROSIS BY DR .MAGDI AWAD SASI 2014 Hepatomegally is present in 50% of cases. [slideshare.net]

  Fullness, discomfort, or pain in the left upper area of the abdomen and early satiety are results of an enlarged spleen pressing on the stomach and other organs. This can lead to weight loss and malnutrition. [mpncanada.com]

  During clinical trials, it was shown to reduce spleen size, abdominal discomfort, early satiety, bone pain, night sweats and itching in MF patients as well as the level of “pro-inflammatory cytokines” in the blood, which may cause some symptoms such as [mpnresearchfoundation.org]

  Patients with advanced disease experience severe constitutional symptoms (general malaise, weight loss, night sweats and low-grade fever), massive splenomegaly (pain, early satiety, splenic infarction, portal hypertension and dyspnoea), progressive marrow [patient.info]

• Hypertension

  MeSH terms: Hypertension Neoplasm Metastasis Hypertension, Pulmonary Familial Primary Pulmonary Hypertension Primary Myelofibrosis Myeloproliferative Disorders Vascular Diseases Cardiovascular Diseases Neoplastic Processes Neoplasms Pathologic Processes [clinicaltrials.gov]

  Aortic Stenosis/Outflow Aortic disease Atrial Fibrillation Bleeding Risk Coronary Artery Disease ECG Echocardiography Heart Failure Hypertension Invasive Hemodynamics Miscellaneous Mitral Regurgitation Mitral Stenosis PCI and Cardiac Surgery Pre-operative [qxmd.com]

  Abstract We studied 25 patients with myelofibrosis with myeloid metaplasia and 19 patients with secondary myelofibrosis associated with pulmonary hypertension (PH). [ncbi.nlm.nih.gov]

  Chronic myeloproliferative diseases (CMPDs) associated with pulmonary hypertension have been included in group five of the clinical classification for pulmonary hypertension, corresponding to pulmonary hypertension for which the aetiology is unclear and [err.ersjournals.com]

  […] failure, pulmonary hypertension, transformation to leukaemia and early death [ 1 ]. [patient.info]

• Heart Disease

  In 13 out of the 22 patients, the elevated pulmonary artery pressure related to heart disease. No obvious reason for the increased pulmonary artery pressure was found in only nine (18.4%) out of the 49 patients. [err.ersjournals.com]

• Hepatomegaly

  Clinical findings Patients are often > age 50, suffer from insidious weight loss, anaemia, and abdominal discomfort due to splenomegaly, often with hepatomegaly; 80% have nonspecific chromosome defects. Diagnosis Bone marrow biopsy. [medical-dictionary.thefreedictionary.com]

  General lymphadenopathy Musculoskeletal osteosclerosis diffuse pattern no bony architectural distortion typical distribution: axial skeleton ribs proximal humerus and femur bone scan may give " superscan " appearance Abdominal hepatomegaly splenomegaly [radiopaedia.org]

  In this situation, splenectomy should not be avoided because of concern over rebound thrombocytosis, loss of hematopoietic capacity, or compensatory hepatomegaly. [theoncologyinstitute.com]

  If hepatomegaly occurs, patients might also have variceal bleeding related to portal hypertension or ascites. B. History Part 2: Prevalence: The peak incidence of primary myelofibrosis (PMF) is between 50-70 years of age. [clinicaladvisor.com]

  Hepatomegaly. Pallor. Petechiae and ecchymosis. Neutropenia may cause opportunistic infection - eg, oral thrush. Lymphadenopathy. Signs of portal hypertension. Gout. [patient.info]

• Myalgia

  Other side effects occurring in 10 percent or more of patients included nausea, pyrexia, hyperuricemia, anemia, asthenia, constipation, cough, dehydration, prolonged electrocardiogram QT, decreased lymphocyte count, myalgia, extremity pain, thrombocytopenia [consultqd.clevelandclinic.org]

• Dizziness

  The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache. These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. [jakafi.com]

  Some of the most common treatment side effects include: nausea dizziness pain or tingling in the hands and feet fatigue shortness of breath fever temporary hair loss Side effects usually go away after your treatment is completed. [healthline.com]

  Possible side effects include flu-like symptoms, headaches, dizziness, mood swings and tiredness. Other drugs Danazol This is a drug that may be given to help improve anaemia (low number of red blood cells). [macmillan.org.uk]

  The most frequent adverse reactions (overall/grade 3 or 4 for ruxolitinib vs placebo) were thrombocytopenia (69.7%/12.9% vs 30.5%/1.3%), anemia (96.1%/45.2% vs 86.8/19.2%), neutropenia (18.7%/7.1% vs 4%/2%), bruising (23.2%/0.6% vs 14.6%/0%), dizziness [ascopost.com]

  Patients are observed for low blood counts, headache, dizziness, bruising or infection. For more about Jakafi, click here (will be directed to the manufacturer’s website). [mpnresearchfoundation.org]

(See Presentation, Workup, and Treatment .) Splenic infarction may occur and results in an acute or subacute onset of severe pain in the left upper quadrant that may be associated with nausea, fever, and referred left shoulder discomfort. [emedicine.medscape.com]

Hyperuricemia is due to enhanced turnover of hematopoietic tissue. 26 Mutation testing Testing for the JAK2 V617F mutation should be performed early during the diagnostic workup of suspected MPNs. [mpncanada.com]

Of patients with Budd-Chiari syndrome (hepatic-inferior vena cava obstruction), 10% to 13% have coexisting PV; therefore, testing for the presence of JAK2 V617F mutation is part of the routine workup for unexplained liver thrombosis. [clevelandclinicmeded.com]

• Neutropenia

  Dose limiting toxicities include thrombocytopenia and neutropenia. [geron.com]

  Grade 4 thrombocytopenia, regardless of attribution to the study drug, occurred in 21% of the patients, grade 4 neutropenia in 18%, and grade 3 anemia in 52%. [nejm.org]

  Splenectomy should be avoided if possible; splenic irradiation has only a temporary effect and can cause severe neutropenia and infection. [merckmanuals.com]

  Splenic irradiation is, at best, temporarily palliative and associated with a significant risk of neutropenia and infection. [theoncologyinstitute.com]

  Grade 3 or 4 neutropenia occurred in 7.1% and 2% of the ruxolitinib and placebo groups, respectively. 28 In both Phase III clinical studies, only 1% of patients reduced or discontinued ruxolitinib due to neutropenia. 28, 29 The median onset of grade 2 [ajhp.org]

• Decreased Platelet Count

  The study by Tefferi et al. [14] also showed some similarities with our study; they found older age group, normal to high platelet count and blast percentage et al. [15] was also in line with our observations. [ijpmonline.org]

  Decreasing platelet counts in ET to below 600 x 10 9 /L can decrease thrombotic complications. 46 High platelet counts (>1,000 x 10 9 /L) are associated with acquired von Willebrand disease resulting from the adsorption of von Willebrand multimers onto [clevelandclinicmeded.com]

• Dry Tap Bone Marrow

  She was subjected to bone marrow examination. Bone marrow aspiration revealed a dry tap. [ijcasereportsandimages.com]

RESULTS: The patients showed excellent response to treatment one month post-radiotherapy, while treatment was well tolerated without severe toxicity. The dimensions of the spleen decreased significantly. [ncbi.nlm.nih.gov]

Treatment Treatment of secondary myelofibrosis treatment Department of Internal Medicine: Department of Hematology Treatment: drug treatment support treatment of surgical treatment Treatment cycle: 1-3 months Cure rate: 80% (A) treatment The disease can [healthfrom.com]

What is the Prognosis for MF? There is no single prognosis for people who suffer from myelofibrosis– the prognosis of MF is different for every patient. [mpnresearchfoundation.org]

Determine DIPSS risk category and prognosis DIPSS score DIPSS risk category Median OS (y) 0 Low Not reached 1 - 2 Intermediate-1 14.2 3 - 4 Intermediate-2 4 5 - 6 High 1.5 IWG-MRT prognostic score for myelofibrosis Applies at the time of diagnosis. 1. [bloodref.com]

Also, these cases may represent a clonal disorder with genetic instability allowing evolution to a more aggressive malignancy. [13] The prognosis in our patient could not be judged following ATT since the child was lost to follow up. [ijcasereportsandimages.com]

Prognosis is poor, with slow progression and death usually within 2-3 years. [radiopaedia.org]

AB - Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. [einstein.pure.elsevier.com]

MVD and MSA were significantly increased in fibrotic marrows regardless of etiology. [ncbi.nlm.nih.gov]

[…] the underlying etiology. [icd10data.com]

This case highlights an unusual etiology for pericardial effusion and tamponade, and further research should be considered with regards to JAK2 mutations in cases of myelofibrosis. [hsrc.himmelfarb.gwu.edu]

Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. [einstein.pure.elsevier.com]

Etiology The etiology of chronic IMF is unknown. Nonrandom chromosome abnormalities such as 9p, 20q-, 13q-, trisomy 8 or 9, or partial trisomy 1q are common, but no cytogenetic abnormality specific to the disease has been identified. [theoncologyinstitute.com]

[…] permission © PEIR, University of Alabama at Birmingham, Department of Pathology Myelofibrosis Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology Causes Differentiating Myelofibrosis from other Diseases Epidemiology [wikidoc.org]

[…] granulocytes in bone marrow, marrow fibrosis, extramedullary hematopoiesis (EMH) Terminology Also called agnogenic (idiopathic) myeloid metaplasia, chronic idiopathic myelofibrosis, myelofibrosis / sclerosis with myeloid metaplasia, idiopathic myelofibrosis Epidemiology [pathologyoutlines.com]

Epidemiology of myeloproliferative neoplasms in the United States. Leukemia & Lymphoma. 2013;Early online: 1-6. [mpninfo.org]

Epidemiology The possible association between PH and CMPDs has been suggested by several case reports and small case series. [err.ersjournals.com]

Epidemiology and clinical relevance of mutations in post-polycythemia vera and post-essential thrombocythemia myelofibrosis. A study on 359 patients of the AGIMM group. Am J Hematol 2016; 91 : 681–686. 7. [nature.com]

[…] prostate) Infective – tuberculosis, fungal infections, HIV Metabolic – Gaucher’s disease Hematological malignancies – chronic myeloid leukemia, multiple myeloma, lymphomas Radiation, radiomimetic drugs Others – Sarcoidosis, congenital osteopetrosis Pathophysiology [pgblazer.com]

Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology Myelofibrosis Microchapters Home Patient Information Overview Historical Perspective Classification Pathophysiology [wikidoc.org]

Metastatic carcinoma or infections with mycobacteria can also cause myelofibrosis. return to top Pathophysiology Fibrosis progressively displaces hematopoietic elements, inculding stem cells, from the marrow. [sharinginhealth.ca]

[…] with myeloid metaplasia, idiopathic myelofibrosis Epidemiology Often occurs in sixth and seventh decades No gender preference Sites Blood and bone marrow Spleen, in cases with EMH Other less common sites include liver, kidney, gastrointestinal tract Pathophysiology [pathologyoutlines.com]

Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007;139:351–62. Web of Science Google Scholar 5. Farolino DL, Rustagi PK, Currie MS, Doeblin TD, Logue GL. [degruyter.com]

Prevention Prevention of secondary myelofibrosis The disease no effective preventive measures, early detection of early diagnosis is the key to prevention and treatment of this disease. [healthfrom.com]

| Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies Case Studies Case # 1 Related chapters Myelophthisic anemia [wikidoc.org]

REFERENCE BOOK Screening for Colorectal Cancer | CTFPHC REFERENCE BOOK Screening for Cognitive Impairment | CTFPHC REFERENCE BOOK Screening for Depression | CTFPHC REFERENCE BOOK Screening for Developmental Delay | CTFPHC Review Canadian Task Force on Preventive [qxmd.com]

Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. [leukaemia.org.au]

[…] way to prevent myelofibrosis, except in cases caused by exposure to radiation or industrial chemicals. [healthcommunities.com]