Samuel Merritt University N 119 Pathophysiology Hematology Concept/Patho May Case Study # 3 Ms. J presents to her physician’s office with complaints of extreme fatigue, weight loss, night sweats and sometimes has a low-grade fever. Her physician determines she has chronic leukemia. Compare and contrast the two main types of chronic leukemia including clinical manifestations. (10 points) Leukemia is cancer of the blood-forming tissues, such as the bone marrow, that most often produces abnormal white blood cells called, leukemic cells (Huether & McCance 564). Chronic leukemia’s are mostly found in adults. In chronic leukemia, the predominant cell is more differentiated but does not function normally, with a relatively slow progression (Huether & McCance 526). The two mains types of chronic leukemia are chronic lymphocytic leukemia (CLL), and chronic myelogenous (CML). Chronic myelogenous leukemia (CML) is a slowly progressing disease with too many blood cells (not lymphocytes) made in the bone marrow (Huether & McCance 530). Chronic lymphocytic leukemia (CLL) is a slow growing cancer in which too many immature lymphocytes (white blood cells) are found mostly in the bone marrow (Huether & McCance 530). CML and CLL incidences increase with age with the most prevalent cases being between 60-80 years of age. CML is one of a group of diseases called myeloproliferative disorders – acquired abnormalities in signaling pathways that lead to the growth factor-independent proliferation – which also include polycythemia vera, primary thrombocytosis, and idiopathic myelofibrosis (invasion of bone marrow by fibrous tissue) (Huether & McCance 530). CML is characterized from other myeloproliferative disorders by the presence of a chimeric (genetically distinct cells) BCR-ABL fusion gene derived from parts of the BCR gene on chromosome 22 and parts of the ABL gene on chromosome 9 (Huether & McCance 530). The only known cause of CML is exposure to radiation (Huether & McCance 530). CLL involves transformation and progressive accumulation of monoclonal B lymphocytes; rarely (less than 5%) are CLL malignancies of Tcell origin (Huether & McCance 530). CLL is derived from a transformation of a partially mature B cell that has not yet encountered antigen (Huether & McCance 530). Chronic Leukemia advances slowly with approximately 70% of individuals with CLL being asymptomatic at the time of diagnosis. The most significant effect of CLL is suppression of humoral immunity and increased infection with encapsulated bacteria (Huether & McCance 531). The level of neutrophil is depressed which adds to the risk of infection (Huether & McCance 531). Approximately 10% of individuals develop a more aggressive malignancy, usually a diffuse large B-cell lymphoma (Huether & McCance 531). In these individuals, extreme fatigue, weight loss, night sweats, low-grade fever, elevated levels of the enzyme lactic acid dehydrogenase, hypercalcemia, anemia, and thrombocytopenia are common (Huether & McCance 531). Individuals with CML may progress through three phases of the disease: a chronic phase lasting 2-5 years during which symptoms may not be apparent, an accelerated phase of 6-18 months during which the primary symptoms develop, and a terminal blast phase (“blast crisis”) with a survival of only 3-6 months (Huether & McCance 531). The accelerated phase is characterized by excessive proliferation and accumulation of malignant cells (Huether & McCance 531). Splenomegaly is prominent in this stage and liver enlargement also occurs. Hyperuricemia is common and produces gouty arthritis and infections, fever and weight loss are often seen (Huether & McCance 531). The terminal blast phase is characterized by rapid and progressive leukocytosis with an increase in basophils (Huether & McCance 531). Towards the later stages of CML the acute effect of it begin to resemble that of AML. She states that she has heard there is a genetic marker that can be used to diagnose leukemia. What is this genetic marker? (1 point) Recent studies are addressing five epigenetic biomarkers to classify CLL, which could result in the use of more targeted therapies for specific subgroups (Heuther & McCance 531). Additionally, investigators report novel recurrent mutations in CLL including SF3B1 and TP53 mutations that are independent of IGHV mutational status, demanding the need for urgent standardization of detection methods (Huether & McCance 531). The cause of this disease is unknown, however, there is association between a genetic marker in the cells that has gone mitotic error. “Philadelphia chromosome, is observed in 95% of those with CML (…) results from a reciprocal translocation between the long arms of chromosomes 9 and 22 (…) leading to an increase of cellular division” (Heuther & McCance, p. 526). What other blood cell related problems are often seen in patients with chronic leukemia? (4 points) Cancer cells may also be found in the lymphoid tissue (Huether & McCance 531). In later stages of CLL cancer cells are sometimes found in the lymph nodes and the disease is called small lymphocytic lymphoma (SLL; also known as CLL/SLL) (Huether & McCance 530). Also classified as non-Hodgkin lymphoma. Chronic leukemia is a disease that progresses at a slow rate. The progress of this disease can be divided in three phases during these phases other blood problems can occur such as lymphadenopathy. Other blood related disease that can developed from chronic leukemia is B cell lymphoma (Huether & McCance, p. 531) which is associated with hypercalcemia defined as high calcium levels in the blood affecting kidneys, heart, and brain functions. Anemia which is an insufficient amount of red blood cells in the blood causing tiredness and weakness, Thrombocytopenia defines as low blood platelets count, and Hyperuricemia an elevated uric acid level in the blood. (Mayo Clinic, 2018). Explain why this individual is more susceptible to infections? (2 points) The most significant effect of CLL is suppression of humoral immunity and increased infection with encapsulated bacteria (Huether & McCance 531). The level of neutrophil is depressed which adds to the risk of infection (Huether & McCance 531). What organs may be infiltrated with leukemic cells? (3 points) Invasion of most organ cells is uncommon but infiltration does occur in lymph nodes, liver, spleen, and salivary glands (Huether & McCance 531). References Huether, S. E., & McCance, K. L. (2017). Understanding pathophysiology (6th ed.). St. Louis, MO: Elsevier Mayo Clinic. (2018). Hypercalcemia. Retrieved from https://www.mayoclinic.org/diseasesconditions/hypercalcemia/symptoms-causes/syc-20355523
